Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
A Phase II Clinical Trial Comparing the Efficacy of RO7198457 Versus Watchful Waiting in Patients With ctDNA-positive, Resected Stage II (High Risk) and Stage III Colorectal Cancer
This is a multi-site, open-label, Phase II, randomized, trial to compare the efficacy of
RO7198457 versus watchful waiting in patients with circulating tumor DNA (ctDNA) positive,
surgically resected Stage II/III rectal cancer, or Stage II (high risk)/Stage III colon
cancer.
Dustin Deming, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04486378
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Inclusion Criteria:
• Patients must be a man or woman of at least 18 years of age.
• Patients must have Stage II/Stage III rectal cancer or Stage II (high risk)/Stage III
colon cancer per American Joint Committee on Cancer 2017 that has been surgically
totally resected (R0 confirmed by pathology report). Stage II (high risk) colon cancer
is defined as Stage II disease with any of the following risk factors for recurrence:
• T4
• Grade ≥ 3.
• Clinical presentation with bowel obstruction or perforation.
• Histological signs of vascular, lymphatic or perineural invasion.
• < 12 nodes evaluated after surgery.
• Patients must have detectable ctDNA prior to start of adjuvant chemotherapy (AdCTx)
(except for the Biomarker Cohort).
• ctDNA assay must be performed through this trial or study BNT000-001 ctDNA screening
protocol.
• Patients must have an Eastern Cooperative Oncology Group Performance Status of 0-1.
• Patients must have adequate hematologic, bone marrow and organ function as defined by
the protocol.
• Adequate tumor material in formalin-fixed paraffin embedded blocks or as sectioned
tissue (only upon approval by sponsor) must be available (as described in the
laboratory manual).
• The patient has started a standard of care AdCTx preferably within 8 weeks but no
later than 10 weeks post-surgery and has completed at least 3 months of treatment of a
3- or a 6-month course of chemotherapy (including rest days).
Exclusion Criteria:
• Patients with uncontrolled intercurrent illness as defined by the protocol.
• Diagnosed microsatellite instability high tumors.
• Prior therapy with any of the following:
• Neo-adjuvant (radio)chemotherapy prior to surgery.
• Treatment with systemic immunosuppressive medication within 2 weeks prior to
initiation of trial treatment or anticipation of need for systemic
immunosuppressive medication during trial treatment, with the exception of low
dose steroids defined as 10 mg oral prednisone (or equivalent).
• Current or recent (within the 28 days prior to randomization) treatment with
another investigational drug.
• Toxicities from previous anti-cancer therapies that have not resolved to baseline
levels or to Grade 1 or less except for alopecia and peripheral neuropathy.
• Patients who developed metastatic disease during screening/receiving standard of care
treatment (not applicable for Exploratory Cohort).
• Patients with known past or current malignancy other than inclusion diagnosis, except
for:
• Cervical carcinoma of Stage 1B or less.
• Non-invasive basal cell or squamous cell skin carcinoma.
• Non-invasive, superficial bladder cancer.
• Prostate cancer with a current prostate-specific antigen level < 0.1 ng/mL.
• Any curable cancer with a complete response of > 2 years duration.
• Patients with known allergies, hypersensitivity, or intolerance to RO7198457 or its
excipients.
• Patients who had major surgery (e.g., surgery requiring general anesthesia) within 4
weeks before screening, or will not have fully recovered from surgery, or have surgery
planned during the time the patient are expected to participate in the trial.
• Patients with positive serology for hepatitis B (unless immune due to vaccination or
resolved natural infection or unless passive immunization due to immunoglobulin
therapy):
• Based on a test for antibodies to hepatitis B core antigens (anti-HBc) and
• Negative test for antibodies to hepatitis B surface antigens (anti-HBs).
• Active Hepatitis C virus (HCV) infection; patients who have completed curative
antiviral treatment with HCV viral load below the limit of quantification are allowed.
• Patients who have a history of human immunodeficiency virus (HIV) antibody positivity,
or tests positive for HIV at screening.
• Patients who have had prior splenectomy.
NOTE: Other protocol defined inclusion/exclusion criteria may apply.
Colorectal Cancer Stage II, Colorectal Cancer Stage III, Colon, Colon and Rectum
A Study to Evaluate Safety, Efficacy of FF-10832 in Combination With Pembrolizumab in Solid Tumors
To confirm a recommended Phase 2 dose (RP2D) of FF-10832 (Gemcitabine Liposome Injection)
given intravenously Day 1 of a 21-day cycle, in combination with 200 mg pembrolizumab given
intravenously Day 1 of the same 21-day cycle, for treatment of advanced solid tumors.
Hamid Emamekhoo, M.D.
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05318573
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Inclusion Criteria:
1. Written informed consent is provided by patient or legally acceptable representative;
2. Age ≥ 18 years;
3. Patient populations:
1. In the Safety Run-in, patients with histologically or cytologically confirmed
advanced or metastatic solid tumors who have disease progression after treatment
with standard therapies for metastatic disease that are known to confer clinical
benefit, or are intolerant to treatment or refuse standard treatment will be
enrolled in therapy
2. In Expansion Phase, patient must have urothelial or NSCLC, and have failed prior
anti-PD-1 or anti-PD-L1
4. Have measurable disease per RECIST 1.1 as assessed by the local site
investigator/radiology
5. Eastern Cooperative Oncology Group performance status of 0 to 1
6. Life expectancy of ≥ 3 months
Exclusion Criteria:
1. Positive urine pregnancy test within 72 hours prior to treatment
2. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks (or 5 half-lives, whichever is shorter) prior to treatment;
3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4, OX 40, CD137), AND was discontinued from that treatment due to a Grade 3 or
higher immune-related adverse event;
4. Has received prior radiotherapy within 2 weeks of start of study treatment.
5. For patients with NSCLC:
1. Patients who have received radiation therapy to the lung that is >30 Gy within 6
months of the first dose of trial treatment are excluded;
2. Patients with mutations (e.g., EGFR mutations or ALK gene rearrangements) will be
excluded unless they have been previously treated with all specific targeted
therapies.
6. Has received a live or live-attenuated vaccine within 30 days prior to the first dose
of study intervention.
7. Has had an allogeneic tissue /solid organ transplant.
Mismatched Related Donor Versus Matched Unrelated Donor Stem Cell Transplantation for Children, Adolescents, and Young Adults With Acute Leukemia or Myelodysplastic Syndrome
This phase III trial compares hematopoietic (stem) cell transplantation (HCT) using
mismatched related donors (haploidentical [haplo]) versus matched unrelated donors (MUD) in
treating children, adolescents, and young adults with acute leukemia or myelodysplastic
syndrome (MDS). HCT is considered standard of care treatment for patients with high-risk
acute leukemia and MDS. In HCT, patients are given very high doses of chemotherapy and/or
radiation therapy, which is intended to kill cancer cells that may be resistant to more
standard doses of chemotherapy; unfortunately, this also destroys the normal cells in the
bone marrow, including stem cells. After the treatment, patients must have a healthy supply
of stem cells reintroduced or transplanted. The transplanted cells then reestablish the blood
cell production process in the bone marrow. The healthy stem cells may come from the blood or
bone marrow of a related or unrelated donor. If patients do not have a matched related donor,
doctors do not know what the next best donor choice is. This trial may help researchers
understand whether a haplo related donor or a MUD HCT for children with acute leukemia or MDS
is better or if there is no difference at all.
Christian Capitini, MD
All
6 Months to 21 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05457556
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Inclusion Criteria:
• PATIENT INCLUSION CRITERIA FOR ENROLLMENT:
• 6 months to < 22 years at enrollment
• Diagnosed with ALL, AML, or MDS or mixed phenotype acute leukemia (MPAL) for which an
allogeneic hematopoietic stem cell transplant is indicated. Complete Remission (CR)
status will not be confirmed at the time of enrollment. CR as defined in these
sections is required to proceed with the actual HCT treatment plan
• Has not received a prior allogeneic hematopoietic stem cell transplant
• Does not have a suitable human leukocyte antigen (HLA)-matched sibling donor available
for stem cell donation
• Has an eligible haploidentical related family donor based on at least intermediate
resolution HLA typing
• Patients who also have an eligible 8/8 MUD adult donor based on confirmatory high
resolution HLA typing are eligible for randomization to Arm A or Arm B.
• Patients who do not have an eligible MUD donor are eligible for enrollment to Arm
C
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
• Co-Enrollment on other trials
• Patients will not be excluded from enrollment on this study if already enrolled
on other protocols for treatment of high risk and/or relapsed ALL, AML, MPAL and
MDS. This is including, but not limited to, COG AAML1831, COG AALL1821, the
EndRAD Trial, as well as local institutional trials. We will collect information
on all co-enrollments
• Patients will not be excluded from enrollment on this study if receiving
immunotherapy prior to transplant as a way to achieve remission and bridge to
transplant. This includes chimeric antigen receptor (CAR) T cell therapy and
other immunotherapies
• PATIENT INCLUSION CRITERIA TO PROCEED TO HCT:
• Karnofsky Index or Lansky Play-Performance Scale >= 60 on pre-transplant evaluation.
Karnofsky scores must be used for patients >= 16 years of age and Lansky scores for
patients =< 16 years of age (within 4 weeks of starting therapy)
• A serum creatinine based on age/gender as follows:
6 months to < 1 year: 0.5 mg/dL (Male); 0.5 mg/dL (Female)
1. to < 2 years: 0.6 mg/dL (Male); 0.6 mg/dL (Female)
2. to < 6 years: 0.8 mg/dL (Male); 0.8 mg/dL (Female)
6 to < 10 years: 1 mg/dL (Male); 1 mg/dL (Female) 10 to < 13 years: 1.2 mg/dL (Male);
1.2 mg/dL (Female) 13 to < 16 years: 1.5 mg/dL (Male); 1.4 mg/dL (Female) >= 16 years:
1.7 mg/dL (Male); 1.4 mg/dL (Female)
• OR
• A 24 hour urine Creatinine clearance >= 60 mL/min/1.73 m^2
• OR
• A glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2. GFR must be performed using
direct measurement with a nuclear blood sampling method OR direct small molecule
clearance method (iothalamate or other molecule per institutional standard)
• Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates
are not acceptable for determining eligibility
• Serum glutamic-oxaloacetic transaminase (SGOT) aspartate aminotransferase [AST] or
serum glutamate pyruvate transaminase (SGPT) aminotransferase [ALT] < 5 x upper limit
of normal (ULN) for age
• Total bilirubin < 2.5 mg/dL, unless attributable to Gilbert's Syndrome
• Shortening fraction of >= 27% by echocardiogram or radionuclide scan (MUGA)
• OR
• Ejection fraction of >= 50% by echocardiogram or radionuclide scan (MUGA), choice of
test according to local standard of care
• Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and
corrected carbon monoxide diffusing capability (DLCO) must all be >= 50% of predicted
by pulmonary function tests (PFTs).
• For children who are unable to perform for PFTs (e.g., due to age or
developmental delay), the criteria are: no evidence of dyspnea at rest, oxygen
(O2) saturation (Sat) > 92% on room air by pulse oximetry, not on supplemental O2
at rest, and not on supplemental O2 at rest
• MPAL in first complete remission (CR1) for whom transplant is indicated. Examples
include those patients who are poorly responsive to ALL therapy (end of induction
failure( IF-MPAL) to ALL induction (see IF-MPAL note below), end of induction MRD ≥ 5%
or end-of-consolidation MRD > 0.01%), as well as patients treated with AML therapy
• IF-MPAL: additional criterion for Induction failure for MPAL ONLY as per ALL1732:
• An increasing number of circulating leukemia cells on 3 or more consecutive CBCs
obtained at daily or longer intervals following day 8 of Induction therapy and
prior to day 29 with confirmation by flow cytometry OR development of new sites
of extramedullary disease, or other laboratory or clinical evidence of refractory
disease or progression prior to the end of Induction evaluation (note that
residual testicular disease at the end of Induction is an exception)
• MPAL in > second complete remission (CR2)
• ALL high-risk in CR1 for whom transplant is indicated. Examples include: induction
failure, treatment failure as per minimal residual disease by flow cytometry > 0.01%
after consolidation and not eligible for AALL1721 or AALL1721 not available/unwilling
to enroll, hypodiploidy (< 44 chromosomes) with MRD+ > 0.01% after induction,
persistent or recurrent cytogenetic or molecular evidence of disease during therapy
requiring additional therapy after induction to achieve remission (e.g. persistent
molecular BCR-ABL positivity), T cell ALL with persistent MRD > 0.01% after
consolidation.
• ALL in CR2 for whom transplant is indicated. Examples include: B-cell: early (=< 36
months from initiation of therapy) bone marrow (BM) relapse, late BM relapse (>= 36
months) with MRD >= 0.1% by flow cytometry after first re-induction therapy; T or
B-cell: early (< 18 months) isolated extramedullary (IEM), late (>= 18 months) IEM,
end-Block 1 MRD >= 0.1%; T-cell or Philadelphia chromosome positive (Ph+): BM relapse
at any time
• ALL in >= third complete remission (CR3)
• Patients treated with chimeric antigen receptor T-cells (CART) cells for whom
transplant is indicated. Examples include: transplant for consolidation of CART, loss
of CART persistence and/or B cell aplasia < 6 months from infusion or have other
evidence (e.g., MRD+) that transplant is indicated to prevent relapse
• AML in CR1 for whom transplant is indicated. Examples include those deemed high risk
for relapse as described in AAML1831:
• FLT3/ITD+ with allelic ratio > 0.1 without bZIP CEBPA, NPM1
• FLT3/ITD+ with allelic ratio > 0.1 with concurrent bZIP CEBPA or NPM1 and with
evidence of residual AML (MRD >= 0.05%) at end of Induction
• Presence of RAM phenotype or unfavorable prognostic markers (other than FLT3/ITD)
per cytogenetics, fluorescence in situ hybridization (FISH), next generation
sequencing (NGS) results, regardless of favorable genetic markers, MRD status or
FLT3/ITD mutation status
• AML without favorable or unfavorable cytogenetic or molecular features but with
evidence of residual AML (MRD >= 0.05%) at end of Induction
• Presence of a non-ITD FLT3 activating mutation and positive MRD (>= 0.05%) at end
of Induction 1 regardless of presence of favorable genetic markers.
• AML in >= CR2
• MDS with < 5% blasts by morphology and flow cytometry (if available) on the
pre-transplant bone marrow evaluation
• Complete remission (CR) is defined as < 5% blasts by morphology and flow cytometry (if
available) on the pre-transplant bone marrow evaluation with minimum sustained
absolute neutrophil count (ANC) of 300 cells/microliter for 1 week or ANC > 500
cells/microliter. We will be collecting data from all approaches to MRD evaluation
performed including NGS and polymerase chain reaction (PCR). It is strongly
recommended that MPAL be evaluated using multidimensional flow cytometry and/or
(KMT2Ar) qt PCR. It is strongly recommended that MPAL be evaluated using
multidimensional flow cytometry and/or (KMT2Ar) qt PCR
• DONOR ELIGIBILITY CRITERIA:
• Matched Unrelated Donors:
Unrelated donor candidates must be matched at high resolution at a minimum of 8/8 alleles
(HLA-A, -B, -C, -DRB1). One-antigen HLA mismatches are not permitted. HLA matching of
additional alleles is recommended according to National Marrow Donor Program (NMDP)
guidelines, but will be at the discretion of local centers
• Haploidentical Matched Family Members:
• Minimum match level full haploidentical (at least 5/10; HLA-A, -B, -C, -DRB1,
-DQB1 alleles). The following issues (in no particular order) should be
considered in choosing a haploidentical donor:
• Absent or low patient donor-specific antibodies (DSA)
• Mean fluorescence intensity (MFI) of any anti-donor HLA antibody by
solid phase immunoassay should be < 2000. Donors with higher levels are
not eligible.
• If a screening assay against pooled HLA antigens is used, positive
results must be followed with specificity testing using a single
antigen assay. The MFI must be < 2000 unless the laboratory has
validated higher threshold values for reactivity for HLA antigens
(such as HLA-C, -DQ, and -DP), that may be enhanced in
concentration on the single antigen assays. Donor anti- recipient
antibodies are of unknown clinical significance and do not need to
be sent or reported.
• Consult with Study Chair for the clinical significance of any
recipient anti-donor HLA antibody.
• If centers are unable to perform this type of testing, please
contact the Study Chair to make arrangements for testing.
• If killer immunoglobulin testing (KIR) is performed: KIR status by mismatch,
KIR-B, or KIR content criteria can be used according to institutional
guidelines.
• ABO compatibility (in order of priority):
• Compatible or minor ABO incompatibility
• Major ABO incompatibility
• CMV serostatus:
• For a CMV seronegative recipient: the priority is to use a CMV
seronegative donor when feasible
• For a CMV seropositive recipient: the priority is to use a CMV
seropositive donor when feasible
• Age: younger donors including siblings/half-siblings, and second degree
relatives (aunts, uncles, cousins) are recommended, even if < 18 years
• Size and vascular access appropriate by center standard for peripheral blood stem cell
(PBSC) collection if needed
• Haploidentical matched family members: screened by center health screens and found to
be eligible
• Unrelated donors: meet eligibility criteria as defined by the NMDP or other unrelated
donor registries. If the donor does not meet the registry eligibility criteria but an
acceptable eligibility waiver is completed and signed per registry guidelines, the
donor will be considered eligible for this study
• Human immunodeficiency virus (HIV) negative
• Not pregnant
• MUD donors and post-transplant cyclophosphamide haplo donors should be asked to
provide BM. If donors refuse and other donors are not available, PBSC is allowed.
TCR-alpha beta/CD19 depleted haplo donors must agree to donate PBSC
• Must give informed consent:
• Haploidentical matched family members: Institution standard of care donor consent
and Protocol-specific Donor Consent for Optional Studies
• Unrelated donors: standard NMDP Unrelated Donor Consent
Exclusion Criteria:
• PATIENT EXCLUSION CRITERIA FOR ENROLLMENT:
• Patients with genetic disorders (generally marrow failure syndromes) prone to
secondary AML/ALL/MPAL with known poor outcomes because of sensitivity to alkylator
therapy and/or TBI are not eligible (Fanconi Anemia, Kostmann Syndrome, Dyskeratosis
Congenita, etc). Patients with Downs syndrome because of increased toxicity with
intensive conditioning regimens.
• Patients with any obvious contraindication to myeloablative HCT at the time of
enrollment
• Female patients who are pregnant are ineligible as many of the medications used in
this protocol could be harmful to unborn children and infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
• PATIENT EXCLUSION CRITERIA TO PROCEED TO HCT:
• Patients with uncontrolled fungal, bacterial, viral, or parasitic infections are
excluded. Patients with history of fungal disease during chemotherapy may proceed if
they have a significant response to antifungal therapy with no or minimal evidence of
disease remaining by computed tomography (CT) evaluation
• Patients with active central nervous system (CNS) leukemia or any other active site of
extramedullary disease at the time of initiation of the conditioning regimen are not
permitted.
• Note: Those with prior history of CNS or extramedullary disease, but with no
active disease at the time of pre-transplant workup, are eligible
• Pregnant or breastfeeding females are ineligible as many of the medications used in
this protocol could be harmful to unborn children and infants
Pembrolizumab vs. Observation in People With Triple-negative Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Pembrolizumab
The phase III trial compares the effect of pembrolizumab to observation for the treatment of
patients with early-stage triple-negative breast cancer who achieved a pathologic complete
response after preoperative chemotherapy in combination with pembrolizumab. Immunotherapy
with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack
the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial
may help researchers determine if observation will result in the same risk of cancer coming
back as pembrolizumab after surgery in triple-negative breast cancer patients who achieve
pathologic complete response after preoperative chemotherapy with pembrolizumab.
Malinda West, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05812807
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Inclusion Criteria:
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Triple Negative Breast Cancer:
• Patients with a history of stage T1cN1-2 or T2-4N0-2 breast cancer according to
the primary tumor-regional lymph node anatomic staging criteria of the American
Joint Committee on Cancer (AJCC), 8th edition as determined by the investigator
in radiologic assessment, clinical assessment or both
• Patients must have no residual invasive disease in the breast or lymph nodes
after the completion of neoadjuvant therapy. Residual ductal carcinoma in situ
(DCIS) is allowed. Isolated tumor cells are considered node-negative
• Estrogen (ER) and progesterone (PR) =< 10%; HER2-negative by American Society of
Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
(immunohistochemistry [IHC] and fluorescence in situ hybridization [FISH])
• If invasive disease was present in both breasts, participation in the study is
permitted as long as the eligibility criteria are met for both tumors/breasts
• Patients must have received neoadjuvant chemotherapy in combination with pembrolizumab
for a minimum of 6 cycles. All systemic chemotherapy and ICI therapy should have been
completed preoperatively
• An interval of no more than 12 weeks between the completion date of the final surgery
and the date of randomization
* Note: Adjuvant radiation can be given on study. If given, it is encouraged to be
given concurrently with pembrolizumab, per investigator discretion. Treatment with
adjuvant pembrolizumab is strongly discouraged prior to participation in this trial,
but if administered (e.g., if patients are awaiting pathology results), pembrolizumab
may be administered for up to 6 weeks post-surgery and must be completed prior to
registration
• Use of investigational anti-cancer agents must be discontinued at time of registration
• Adequate excision: Surgical removal of all clinically evident disease in the breast
and lymph nodes as follows:
• Breast surgery: Total mastectomy or breast-conserving surgery with histologically
negative margins, including no ink on tumor for DCIS, at the time of excision
** For patients who undergo breast-conserving surgery, the margins of the
resected specimen must be histologically free of ductal carcinoma in-situ (DCIS)
as determined by the local pathologist. If pathologic examination demonstrates
DCIS at the line of resection, additional operative procedures may be performed
to obtain clear margins. If DCIS is still present at the resected margin after
re-excision(s), the patient must undergo total mastectomy to be eligible.
Patients with margins positive for classic lobular carcinoma in situ (LCIS) are
eligible without additional resection
• Lymph node surgery:
• For a patient with clinically N0 disease, a sentinel lymph node biopsy
should have been performed at time of surgical evaluation, and if
pathologically node positive, the patient is no longer eligible. Isolated
tumor cells are considered node-negative
• For a patient with clinically N1 disease at diagnosis (with positive results
from a fine-needle aspiration, core biopsy, or sentinel node biopsy
performed prior to preoperative therapy) additional surgical evaluation of
the axilla following preoperative therapy is required
*** If they become cN0 (no palpable adenopathy), then a sentinel lymph node
biopsy could have been performed at time of surgery (axillary dissection
would also be permitted); if the sentinel lymph node biopsy is positive, the
patient is no longer eligible
• If sentinel node biopsy performed before preoperative therapy was negative,
no additional surgical evaluation of the axilla is required after
preoperative therapy. If sentinel node biopsy performed before preoperative
therapy was positive, an ALND is required after preoperative therapy
• If the only sentinel node identified by isotope scan is in the internal
mammary chain, surgical evaluation of the axilla is still required
• If sentinel node evaluation after preoperative therapy is negative, no
further additional surgical evaluation of the axilla is required
• Axillary dissection without sentinel node evaluation is permitted as the
initial or sole axillary evaluation after preoperative therapy
• If breast-conserving surgery was performed but patient will not be receiving breast
radiation, the patient is not eligible
• Not pregnant and not nursing, because this study involves an agent whose genotoxic,
mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
Therefore, for women of childbearing potential only, a negative serum or urine
pregnancy test done =< 7 days prior to randomization is required
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Platelet Count >= 100,000/mm^3
• Estimated glomerular filtration rate (eGFR) >= 15 mL/min/1.73m^2
• Total Bilirubin =<1.5 x upper limit of normal (ULN)
* Patients with Gilbert's disease with a total bilirubin =< 2.5 x ULN and direct
bilirubin within normal limits are permitted
• Aspartate aminotransferase (AST) serum aspartate aminotransferase [SGOT] / alanine
aminotransferase (ALT) serum glutamic pyruvic transaminase [SGPT] =< 3 x institutional
ULN
• Patients must be willing to provide tumor tissue from the diagnostic core biopsy. If
inadequate tumor tissue is available, patients are still eligible to participate in
the trial
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months prior to registration are
eligible for this trial
Exclusion Criteria:
• No stage IV (metastatic) breast cancer
• No history of any prior (ipsi- or contralateral) invasive breast cancer. Prior DCIS is
allowed
• No evidence of recurrent disease following preoperative therapy and surgery
• No known active liver disease, e.g. due to hepatitis B virus (HBV), hepatitis C virus
(HCV), autoimmune hepatic disorders, or sclerosing cholangitis
• No history of intolerance, including Grade 3 or 4 infusion reaction or
hypersensitivity to pembrolizumab or murine proteins or any components of the product
* Note: Prior immune-related adverse events (irAEs) are allowed if they resolved and
the patient tolerated subsequent therapy without requiring chronic steroids for the
irAE
• No medical conditions that require chronic systemic steroids (>10 mg prednisone daily
or equivalent) or any other form of immunosuppressive medications and has required
such therapy in the last two years. Replacement therapy (e.g. thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
etc.) is not considered a form of systemic therapy
• Patients who are unable or unwilling to comply with the requirements of the protocol
per investigator assessment are not eligible
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Early Stage Triple-Negative Breast Carcinoma, Breast
Testing the Effectiveness of an Anti-cancer Drug, Triapine, When Used With Targeted Radiation-based Treatment (Lutetium Lu 177 Dotatate), Compared to Lutetium Lu 177 Dotatate Alone for Metastatic Neuroendocrine Tumors
This phase II trial compares the effect of adding triapine to lutetium Lu 177 dotatate versus
lutetium Lu 177 dotatate alone (standard therapy) in shrinking tumors or slowing tumor growth
in patients with neuroendocrine tumors that have spread from where they first started
(primary site) to other places in the body (metastatic). Triapine may stop the growth of
tumor cells by blocking some of the enzymes needed for deoxyribonucleic acid synthesis and
cell growth. Lutetium Lu 177 dotatate is a radioactive drug. It binds to a protein called
somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177
dotatate builds up in these cells and gives off radiation that may kill them. It is a type of
radioconjugate and a type of somatostatin analog. Giving triapine in combination with
lutetium Lu 177 dotatate may be more effective at shrinking tumors or slowing tumor growth in
patients with metastatic neuroendocrine tumors than the standard therapy of lutetium Lu 177
dotatate alone.
Sam Lubner, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05724108
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Inclusion Criteria:
• Patients must have metastatic, histologically confirmed well-differentiated
neuroendocrine tumor with positive gallium 68 DOTATATE or copper 64 DOTATATE scan.
Lesions on dotatate scan will be considered positive if the standardized uptake volume
maximum (SUVmax) of target lesion is > 2 times standardized uptake value (SUV) mean of
normal liver parenchyma. Patients with lung neuroendocrine tumors (NETs) are excluded
from the trial
• Patients must have progressive disease based on RECIST criteria, version 1.1 evidenced
with CT scans/MRI obtained within 24 months from enrollment
• Patients must have measurable disease per RECIST 1.1
• Failure of at least one prior systemic cancer treatment with somatostatin analogs
• No prior exposure to peptide receptor radionuclide therapy
• Recovered from adverse events of previously administered therapeutic agents (i.e., to
grade 2 or less toxicity) according to Common Terminology Criteria for Adverse Events
(CTCAE) 5.0
• Age >= 18 years
• Because no dosing or adverse event data are currently available on the use of
triapine in combination with lutetium Lu 177 dotatate in patients < 18 years of
age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 x institutional ULN
• Serum creatinine =< 1.5 x institutional ULN. Creatinine > 1.5 ULN will require a
measured creatinine clearance (CrCl) > 50 ml/min to qualify
• Hemoglobin > 5.0 mmol/L (> 8.0 g/dL)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases and off steroids are eligible if follow-up
brain imaging after central nervous system (CNS)-directed therapy shows no evidence of
progression for at least 4 weeks prior to enrollment in the study. Patients with a
history of brain metastases must have a head CT with contrast to document stable
disease prior to enrollment in the study
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
• Pregnancy precaution: Men and women should avoid pregnancy for seven months after the
date of their last treatment with lutetium Lu 177 dotatate. It is noteworthy that
beta-human chorionic gonadotropin (beta-HCG) may be secreted by a small percentage of
NETs, such that, in addition to being a pregnancy marker, it also is a tumor marker.
Consequently, NET female patients with positive beta-HCG (> 5 mIU/mL) at baseline can
be eligible to enter the study and receive treatment if pregnancy can be excluded by
lack of expected doubling of beta-HCG and negative pelvic ultrasound. Normally, in
pregnant subjects beta-HCG doubles every 2 days during the first 4 weeks of pregnancy
and every 3.5 days by weeks 6 to 7. Women of childbearing potential include any female
who has experienced menarche and who has not undergone successful surgical
sterilization (hysterectomy, bilateral tubal ligation, or bilateral ovariectomy) or is
not postmenopausal (defined as amenorrhea > 12 consecutive months, and for women on
hormone replacement therapy, only with a documented plasma follicle-stimulating
hormone [FSH] level > 35 mIU/mL). Even women who are using oral, implanted, or
injected contraceptive hormones, an intrauterine device (IUD), or barrier methods
(diaphragm, condoms, spermicidal) to prevent pregnancy, are practicing abstinence or
where the partner is sterile (e.g., vasectomy) should be considered to be of
childbearing potential. Postmenopausal women who have fertilized eggs implanted are
also considered to be of childbearing potential. Acceptable methods of contraception
may include total abstinence at the discretion of the Investigator in cases where the
age, career, lifestyle, or sexual orientation of the patient ensures compliance.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods)
and withdrawal are not acceptable methods of contraception. Reliable contraception
(hormonal or barrier method of birth control; abstinence) should be maintained
throughout the study and for 7 months after study treatment discontinuation. All men
and women of childbearing potential and male partners must use a double-barrier method
of birth control or practice continuous abstinence from heterosexual contact
throughout the study and for seven months after the end of the last treatment
• Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
• Patients who have not recovered from adverse events of previously administered
therapeutic agents (i.e., have residual toxicities > grade 2) according to CTCAE 5.0,
with the exception of alopecia
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to triapine or lutetium Lu 177 dotatate
• Patients with uncontrolled intercurrent illness
• Uncontrolled congestive heart failure (New York Heart Association [NYHA] III, IV)
• Pregnant women are excluded from this study because triapine is a ribonucleotide
reductase (RNR) inhibitor and lutetium Lu 177 dotatate is a peptide receptor
radionuclide therapy with the potential for teratogenic or abortifacient effects.
Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with triapine and lutetium Lu 177 dotatate,
breastfeeding should be discontinued if the mother is treated with triapine and
lutetium Lu 177 dotatate and for 2.5 months following the last treatment
• Inability to swallow oral medications or gastrointestinal disease limiting absorption
of oral agents
• Patients with any other significant condition, currently uncontrolled by treatment,
which may interfere with completion of the study
Metastatic Neuroendocrine Tumor, Other Endocrine System, Endocrine cancers
KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors (FIT-001)
This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess
KO-2806, a farnesyl transferase inhibitor (FTI), as a monotherapy and in combination, in
adult patients with advanced solid tumors.
Justine Bruce, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT06026410
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Inclusion Criteria:
• At least 18 years of age.
• Histologically or cytologically confirmed advanced solid tumors
• Arm #1 (Monotherapy): HRAS-mutant and/or amplified tumors (any solid tumor type);
HRAS overexpression (only for HNSCC tumors); KRAS and/or NRAS, and/or HRAS-mutant
and/or amplified NSCLC or CRC; KRAS-mutant and/or amplified PDAC
• Arm #2 (Combination): Must have received at least 1 prior systemic therapy with
IO-based treatment for locally advanced or metastatic RCC with predominantly
clear cell subtype
• Arm #3 (Combination): Must have KRAS G12C-mutant locally advanced or metastatic
NSCLC and have received at least 1 prior systemic therapy for advanced or
metastatic NSCLC
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Karnofsky Performance Status of 70 or higher with no clinically significant
deterioration over the previous 2 weeks.
• Acceptable liver, renal, endocrine, and hematologic function.
• Other protocol-defined inclusion criteria may apply.
Exclusion Criteria:
• Ongoing treatment with certain anticancer agents.
• Prior treatment with an FTI or HRAS inhibitor.
• Major surgery, other than local procedures, within 28 days prior to Cycle 1 Day 1,
without complete recovery.
• Spinal cord compression, leptomeningeal disease, or clinically active CNS metastases.
• Toxicity (excluding alopecia) from prior therapy that has not been completely resolved
to baseline at the time of consent.
• Active or prior documented autoimmune or inflammatory disorders within the past 5
years prior to Cycle 1 Day 1 (with exceptions).
• Active, uncontrolled bacterial, viral, or fungal infections requiring systemic
therapy.
• Inability to swallow, impairment of gastrointestinal (GI) function or GI disease that
may significantly alter the absorption of the trial drugs.
• Inadequate cardiac and/or vascular function, including receipt of treatment for
unstable angina, myocardial infarction, and/or cerebro-vascular attack within the
prior 6 months, mean QTcF ≥470 ms, or Class II or greater congestive heart failure.
• Other invasive malignancy within 2 years.
• Other protocol-defined exclusion criteria may apply.
Solid Tumors With HRAS Alterations, Non Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Clear Cell Renal Cell Carcinoma (ccRCC), Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
A Study of NDI 1150-101 in Patients With Solid Tumors
This study is to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose
(RP2D) and to investigate the safety, pharmacokinetics (PK), pharmacodynamics, and
preliminary antitumor activity of NDI-101150 given as monotherapy or in combination with
pembrolizumab in adult patients with advanced solid tumors.
Hamid Emamekhoo, M.D.
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05128487
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Key
Inclusion Criteria:
• Life expectancy of ≥ 12 weeks
• Measurable or non-measurable disease for Dose Escalation; measurable disease using
RECIST v1.1 is required for Dose Expansion
• Recovered from prior therapy to Grade ≤ 1 or return to baseline status (except for
alopecia)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patients with adequate bone marrow, kidney and liver function
• Last dose of previous anticancer therapy ≥ 4 weeks prior to first dose of NDI-101150;
includes prior anti-PD-1 or anti-PD-L1 therapy, other anticancer therapy,
radiotherapy, or surgical intervention
• For Dose Escalation Phase Only (Dose Escalation, Monotherapy and Combination Therapy):
Histologically or cytologically confirmed advanced or metastatic solid tumors for whom
no standard therapies are available or refractory to standard therapy
• For Dose Expansion Phase (Dose Expansion, Monotherapy and Combination Therapy):
Willing to consent to required tumor biopsy(ies). Histologically or cytologically
confirmed advanced or metastatic G/GEJ, NSCLC or RCC for which no standard therapy is
available or are refractory to standard therapy
Key
Exclusion Criteria:
• Previous solid organ or hematopoietic cell transplant
• Central nervous system (CNS) malignant disease not previously treated, active
leptomeningeal disease, uncontrolled symptomatic CNS involvement, or CNS malignant
disease requiring steroid or other therapeutic intervention
• Prior anticancer therapy within 2-6 weeks of trial start (depending on nature of
therapy).
• Clinically significant cardiovascular disease
• History of severe hypersensitivity reaction to treatment with monoclonal antibody(ies)
(for combination therapy cohorts only)
• History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis
(including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans,
cryptogenic organizing pneumonia, etc.), or evidence of history of pneumonitis on
chest computed tomography scan in the last 6 months
• Known additional malignancy that is active and/or in progression requiring treatment
• Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function,
unstable pulmonary condition, uncontrolled diabetes, thromboembolic event within the
past 3 months) or any important medical or psychiatric illness or abnormal laboratory
finding
• Unable to discontinue medications that are strong inducers or inhibitors of CYP3A4
and/or CYP2C8
• History of severe irAE that led to permanent discontinuation of prior immunotherapy
• History of recent Grade >/= 3 irAE or any Grade 4 life-threatening irAE, neurologic or
ocular AE of any grade while receiving prior immunotherapy
NOTE: Other protocol defined Inclusion and Exclusion criteria may apply.
Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
The goal of this clinical trial is to use new imaging methods to help in finding out whether
the imaging shows that there is a tumor in people with a brain metastasis. The main question
it aims to answer is whether positron emission tomography (PET) and magnetic resonance
imaging (MRI) find cancerous tissue better than other types of imagining.
Participants will undergo a single PET/MRI scan, followed by a separate MRI scan with a
tracer. Study participation will last about 3 hours.
Michael Veronesi
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT06159335
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Inclusion Criteria:
• Age 18 years or older
• Able and willing to provide informed consent
• Has a brain metastasis diagnosis with at least one single visible contrast enhancing
metastatic lesion on brain MRI
• Received at least one immune checkpoint inhibitor for treatment of the malignancy in
the past 6 months
• Any other concurrent therapy or prior administered therapy, which would include prior
surgery, radiation, immunotherapy, or chemotherapy are not an exclusion.
• Has had at least one previous standard-of-care MRI imaging within the past 60 days for
assessment of disease location and extent with increasing enhancement where the
question of tumor recurrence versus treatment related change are a clinical question.
• Be able to lie still for 30-60 minutes during the imaging procedure
• Willing and able to undergo PET/MRI
Exclusion Criteria:
• Subject unable or unwilling to provide informed consent
• Subject is pregnant
• Subject with contraindication(s) to or inability to undergo a PET or MRI
• Known allergy to 18F-Fluciclovine or any of its excipients
Brain Metastasis, Radiation Therapy, Immunotherapy, Active, Brain and Nervous System, Brain/Central Nervous System
To Evaluate Efficacy and Safety of Serplulimab + Chemotherapy (Carboplatin- Etoposide) in US Patients With ES-SCLC
This is a randomized, open-label study of Serplulimab plus chemotherapy
(Carboplatin-Etoposide) in comparison with Atezolizumab plus chemotherapy in previously
untreated US patients with ES-SCLC.
Subjects in this study will be randomized to arm A or B at 1:1 ratio as follows:
- Arm A (Serplulimab): Serplulimab + chemotherapy (carboplatin-etoposide)
- Arm B (control): Atezolizumab + chemotherapy (carboplatin-etoposide)
Toby Campbell, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05468489
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Inclusion Criteria:
Voluntary participation in clinical studies.
Male or female aged ≥ 18 years at the time of signing the ICF.
Histologically or cytologically diagnosed with ES-SCLC (according to the Veterans
Administration Lung Study Group staging system).
No prior systemic therapy for ES-SCLC.
At least one measurable lesion as assessed according to RECIST 1.1 within 4 weeks prior to
randomization.
Major organs are functioning well.
Every effort should be made to provide tumor tissues for the determination of PD-L1
expression.
An ECOG PS score of 0 or 1.
An expected survival ≥ 12 weeks.
Subjects with prior denosumab use that can and agree to switch to bisphosphonate therapy
for bone metastases starting prior to randomization and throughout treatment.
Participant must keep contraception.
Exclusion Criteria:
Histologically or cytologically confirmed mixed SCLC.
Known history of severe allergy to any monoclonal antibody.
Known hypersensitivity to carboplatin or etoposide.
Patients with myocardial infarction within half a year before the first dose of the study
drug, poorly controlled arrhythmia.
Pregnant or breastfeeding females.
Patients with a known history of psychotropic drug abuse or drug addiction.
Patients who have other factors that could lead to the early termination of this study
based on the investigator's judgment.
Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Patients With Metastatic Breast Cancer (ELEVATE)
This is a multicenter, Phase 1b/2 trial. The phase 1b part of the trial aims to determine the
RP2D of elacestrant when administered in combination with alpelisib, everolimus, palbociclib,
abemaciclib, and ribociclib. The Phase 2 part of the trial will evaluate the efficacy and
safety of the various combinations in patients with ER+/HER2- advanced/metastatic breast
cancer.
Marina Sharifi, MD, PhD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05563220
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Inclusion Criteria:
1. Patient has signed the informed consent before all study specific activities are
conducted.
2. Women or men aged ≥18 years (or the minimum age of consent in accordance with the
local law), at the time of informed consent signature. Female patients may be of any
menopausal status.
• Postmenopausal status is defined by:
1. Age ≥60 years
2. Age <60 years and amenorrhea for 12 or more months (in the absence of
chemotherapy, tamoxifen, toremifene, or ovarian suppression) or a
follicle-stimulating hormone (FSH) value >40 mIU/mL and an estradiol
value<40 pg/mL (140 pmol/L) or in postmenopausal ranges per local reference
ranges
3. Documentation of prior surgical sterilization (i.e., bilateral tubal
ligation, total hysterectomy, or bilateral oophorectomy, at least 1 month
before first dose of trial therapy).
• Premenopausal and perimenopausal women (who do not fit postmenopausal criteria)
and men must be concurrently receiving a luteinizing hormone-releasing hormone
(LHRH) agonist initiated at least 4 weeks before the start of trial therapy and
are planning to continue LHRH agonist treatment during the study treatment.
• For perimenopausal women to be considered of non-childbearing potential, FSH
levels must be >40 mIU/ml.
3. Histopathological or cytological confirmed ER+, HER2-, breast cancer, per local
laboratory, as per the American Society of Clinical Oncology (ASCO)/College of
American Pathologists(CAP) guidelines (Allison et al, 2020, Wolff et al, 2018). Note:
In the context of this trial, ER status will be considered positive if ≥10% of tumor
cells demonstrate positive nuclear staining by immunohistochemistry, with or without
PGR positivity. .
4. At least 1 not previously irradiated measurable lesion as per RECIST version 1.1
and/or at least 1 lytic or mixed (lytic +sclerotic) bone lesion with identifiable soft
tissue components meeting the definition of measurability by RECIST version 1.1 that
can be evaluated by CT or MRI; patients with sclerotic/osteoblastic bone lesions only
in the absence of measurable disease are not eligible.
5. ECOG performance status of 0 or 1.
6. Patient has adequate bone marrow and organ function, as defined by the following
laboratory values:
1. Absolute neutrophil count (ANC) ≥1.5 × 10^9/L
2. Platelets ≥100 × 10^9/L
3. Hemoglobin ≥9.0 g/dL
4. Potassium, sodium, calcium (corrected for serum albumin) and magnesium CTCAE
grade ≤1
5. Creatinine is ≤ 1.5 x ULN or if creatinine is > 1.5 x ULN, then creatinine
clearance must be ≥50 mL/min based on the Cockcroft-Gault formula. Note: C-G
formula:
• Creatinine clearance (male) = ([140-age in years] × weight in kg)/ ([serum
creatinine in mg/dL] × 72)
• Creatinine clearance (female) = (0.85 × [140-age in years] × weight in kg)/
([serum creatinine in mg/dL] × 72)
6. Serum albumin ≥3.0 g/dL (≥30 g/L)
7. In absence of liver metastases, alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) ≤ 3.0 × ULN. If the patient has liver metastases, ALT and
AST ≤ 5 × ULN
8. Total serum bilirubin <1.5 × ULN except for patients with Gilbert's syndrome who
may be included if the total serum bilirubin is ≤3.0 × ULN or direct bilirubin ≤
1.5 × ULN.
Exclusion Criteria:
1. Active or newly diagnosed CNS metastases, including meningeal carcinomatosis. Note:
Patients with stable brain or subdural metastases are allowed if the patient has
completed local therapy and was on a stable or decreasing dose of corticosteroids at
baseline for management of brain metastasis for at least 4 weeks before starting
treatment in this study. The dose must be ≤2.0 mg/day of dexamethasone or equivalent.
Any signs (e.g., radiologic) or symptoms of brain metastases must be stable for at
least 4 weeks before starting study treatment.
2. Patients with advanced, symptomatic visceral spread, that are at risk of
life-threatening complications in the short term, including massive uncontrolled
effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver
involvement >50%.
3. Prior chemotherapy or elacestrant in the advanced/metastatic setting.
4. Patients with known germline BRCA mutation without prior treatment with a PARP
inhibitor before study entry.
5. Prior therapy with elacestrant or other investigational selective estrogen receptor
degraders (SERDs), or investigational alike agents such as selective estrogen receptor
modulators (SERM), selective estrogen receptor covalent antagonists (SERCANs),
complete estrogen receptor antagonists (CERANs), and proteolysis-targeting chimeras
(PROTACs), in the metastatic setting. Prior treatment with fulvestrant is not
exclusionary as it is an approved medication.
6. Patient has a concurrent malignancy or history of invasive malignancy within 3 years
of enrollment, except basal or squamous cell skin cancer, superficial bladder cancer,
or carcinoma in situ of the cervix that has completed curative therapy. Other
malignancies with low risk of recurrence may be considered eligible with Sponsor
approval.
7. Uncontrolled significant active infections. • Patients with HBV and/or HCV infection
must have undetectable viral load during screening.
• Patients known to be HIV+ are allowed if they have undetectable viral load at
baseline.
8. Documented pneumonitis/ILD prior to Cycle 1 Day 1.
9. Major surgery within 28 days before starting trial therapy.
10. Inability to take oral medications, refractory or chronic nausea, gastrointestinal
conditions (including significant gastric or bowel resection), history of
malabsorption syndrome, or any other uncontrolled gastrointestinal condition that
impact the absorption of the study drug.
11. Known intolerance to elacestrant or any of its excipients.
12. Pregnant and breast-feeding women are excluded from the study. In addition, women of
childbearing potential are excluded who:
• Within 28 days before starting trial therapy, did not use a highly effective method
of contraception.
• Do not agree to use a highly effective method of contraception (Appendix F) or
abstain from heterosexual intercourse throughout the entire study period and for 120
days after trial therapy discontinuation.
13. Men or women who do not agree to abstain from donating sperm or ova, or to use a
highly effective method of contraception, during the course of the treatment period
and for 120 days after the last dose of study treatment.
14. Patient is currently receiving or received any of the following medications prior to
first dose of trial therapy:
• Anti-cancer therapy within 14 days (28 days for anticancer antibody based treatment)
or 5 half-lives, whichever is shorter.
Please note: Toxicity from prior therapy must be resolved to NCI CTCAE version 5.0
Grade ≤1, except alopecia and peripheral sensory neuropathy (Grade ≤2).
• Known strong or moderate inducers or inhibitors of cytochrome P450 (CYP) 3A4 within
14 days or 5 half-lives, whichever is shorter, (refer to
http://medicine.iupui.edu/clinpharm/ddis/ or
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interac
tions-table-substrates-inhibitors-and-inducers).
• Herbal preparations/medications within 7 days. These include, but are not limited
to, St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone
(DHEA), yohimbe, saw palmetto, and ginseng.
• Vaccination, including but not limited to vaccination against COVID-19, during the 7
days prior to randomization.
15. Evidence of ongoing alcohol or drug abuse as assessed by the investigator.
16. Any severe medical or psychiatric condition that, in the Investigator's opinion, would
preclude the patient's participation in a clinical study.
Additional Eligibility for the Alpelisib Combination (Phase 1b and Arm A)
Inclusion:
In general, the SmPC of the respective combination drug should be consulted for
instructions/restrictions with respect to interactions with concomitant medications.
1. PIK3CA mutation by local laboratory assessment.
2. One or up to two prior hormonal therapies in the advanced or metastatic setting, one
of which was in combination with a CDK4/6 inhibitor.
Exclusion:
1. Prior therapy with alpelisib or any other PI3K inhibitor.
2. Type 1 diabetes or uncontrolled type 2 diabetes (fasting plasma glucose level of >140
mg/dL [7.7 mmol/L], or glycosylated hemoglobin [HbA1c] level of >6.4%).
3. Known intolerance to alpelisib or any of its excipients.
4. Patient is currently receiving or received drugs known to be a BCRP inhibitor within
14 days or 5 half-lives, whichever is shorter, prior to first dose of trial therapy
5. Patient has ongoing osteonecrosis of the jaw from previous or concurrent treatment
with bisphosphonates or denosumab
Additional Eligibility for the Everolimus Combination (Phase 1b and Arm B)
Inclusion:
1. One or up to two prior hormonal therapies in the advanced or metastatic setting, one of
which was in combination with a CDK4/6 inhibitor.
Exclusion:
1. Prior therapy with everolimus.
2. Known intolerance to everolimus or any of its excipients.
Additional Eligibility for the Abemaciclib Combination (Arm C)
Inclusion:
1. One or up to two prior hormonal therapies in the advanced or metastatic setting, one of
which was in combination with a CDK4/6 inhibitor.
Exclusion:
1. Prior therapy with abemaciclib in the advanced or metastatic setting. Adjuvant therapy
with abemaciclib is exclusionary if the patient relapsed within the past 12 months.
2. Known intolerance to abemaciclib or any of its excipients.
Additional Eligibility for the Ribociclib Combination (Phase 1b and Arm C)
Inclusion:
1. One or up to two prior hormonal therapies in the advanced or metastatic setting, one of
which was in combination with a CDK4/6 inhibitor.
Exclusion:
1. Prior therapy with ribociclib in the metastatic setting. Prior adjuvant therapy with
ribociclib is also exclusionary if the patient relapsed within the past 12 months.
2. Known intolerance to ribociclib or any of its excipients.
3. QTcF values ≥450 msec.
4. Patients who already have or who are at significant risk of developing QTc
prolongation, including patients with:
• Long QT syndrome
• Uncontrolled or significant cardiac disease including recent (6 months)
myocardial infarction, congestive heart failure, unstable angina, and
brady-arrhythmias
• Electrolyte abnormalities
5. Patient is currently receiving or received drugs known to prolong QT interval within
14 days or 5 half-lives, whichever is shorter, before the first dose of trial therapy.
Additional Eligibility for the Palbociclib Combination (Phase 1b)
Inclusion:
1. One or up to two prior hormonal therapies in the advanced or metastatic setting, one of
which was in combination with a CDK4/6 inhibitor.
Exclusion:
1. Prior therapy with palbociclib in the metastatic setting.
2. Known intolerance to palbociclib or any of its excipients
Additional Eligibility for the Palbociclib Combination (Arm D)
Inclusion:
1. One or up to two prior hormonal therapies in the advanced or metastatic setting.
Exclusion:
1. Prior therapy with a CDK4/6i in the metastatic setting.
2. Known intolerance to palbociclib or any of its excipients.
Additional Eligibility for the Abemaciclib Combination (Arm D)
Inclusion:
1. One or up to two prior hormonal therapies in the advanced or metastatic setting.
Exclusion:
1. Prior therapy with any CDK4/6i in the metastatic setting.
2. Known intolerance to abemaciclib or any of its excipients.
Additional Eligibility for Ribociclib Combination (Arm D)
Inclusion:
1. One or up to two prior hormonal therapies in the advanced or metastatic setting.
Exclusion:
1. Prior therapy with a CDK4/6i in the advanced or metastatic setting.
2. Known intolerance to ribociclib or any of its excipients.
3. QTcF values ≥450 msec.
4. Patients who already have or who are at significant risk of developing QTc
prolongation, including patients with:
• Long QT syndrome
• Uncontrolled or significant cardiac disease including recent (6 months)
myocardial infarction, congestive heart failure, unstable angina, and
brady-arrhythmias
• Electrolyte abnormalities
5. Patient is currently receiving or received drugs known to prolong QT interval within
14 days or 5 half-lives, whichever is shorter, before the first dose of trial therapy.
Testing the Use of Fulvestrant and Binimetinib Targeted Treatment for NF1 Mutation in Hormone Receptor-Positive Metastatic Breast Cancer (A ComboMATCH Treatment Trial)
This phase II ComboMATCH treatment trial compares the usual treatment alone (fulvestrant) to
using binimetinib plus the usual treatment in patients with hormone receptor positive breast
cancer that has spread from where it first started to other places in the body (metastatic)
and has an NF1 genetic change. Fulvestrant is a hormonal therapy that binds to estrogen
receptors in tumor cells, resulting in estrogen receptor destruction and decreased estrogen
binding, which may inhibit the growth of estrogen-sensitive tumor cells. Binimetinib is a
targeted therapy that may stop the growth of tumor cells by blocking some of the enzymes
needed for cell growth. The addition of binimetinib to fulvestrant in breast cancers with an
NF1 genetic change could increase the percentage of tumors that shrink as well as lengthen
the time that the tumors remain stable (without progression) as compared to fulvestrant
alone.
Mark Burkard, MD, PhD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05554354
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Inclusion Criteria:
• Patient must have enrolled onto EAY191 and must have been given a treatment assignment
to ComboMATCH to EAY191-N2 based on the presence of an actionable mutation as defined
in EAY191
• The patient must be enrolled on the ComboMATCH Master Registration Trial EAY191
• Note: Patients must fulfill all eligibility criteria outlined in the ComboMATCH
Registration Trial EAY191 at the time of registration to EAY191-N2. This includes
submission of next-generation sequencing (NGS) data from one of the National
Cancer Institute (NCI) credentialed designated laboratories for all potential
patients prior to treatment trial assignment. Copy number and allele frequency
cutoff as per the Registration protocol
• Patients must have disease that can be safely biopsied and agree to a pre-treatment
biopsy or, if disease cannot be safely biopsied, have archival tissue available from
within 12 months prior to the date of registration on the ComboMATCH registration
trial (EAY191)
• Please note the current actionable marker of interest (aMOI)/actionable
alteration list for this treatment trial can be found on the Cancer Trial Support
Unit (CTSU) ComboMATCH Registration protocol page
• Please note novel/Dynamic aMOI can be submitted for review per the process
described in the ComboMATCH Registration protocol
• A COMBOMATCH TREATMENT TRIAL EAY191-N2 ELIGIBILITY CRITERIA:
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Histologically or cytologically confirmed invasive breast carcinoma
• Confirmed metastatic disease by either imaging or tissue diagnosis
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and
one additional lesion that can be biopsied (primary, metastatic both allowed)
• Patients must have inactivating or inferred inactivating NF1 alterations detected in
tumor as determined by the ComboMATCH screening assessment
• The tumor must have been determined to be estrogen receptor (ER) and/or progesterone
receptor (PgR) positive assessed by current American Society of Clinical Oncology
(ASCO)/College of American Pathologists (CAP) guideline recommendations for hormone
receptor testing. Patients with >= 1% ER or PgR staining by immunohistochemistry (IHC)
are considered positive
• The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines
• Prior use of CDK4/6 inhibitor(i) is required
• Prior use of fulvestrant regardless of duration is allowed and will determine
treatment assignment
• Up to one line of chemotherapy in metastatic setting is allowed
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/ mm^3
• Hemoglobin level >= 10 g/dL
• Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
• Total bilirubin level =< institutional upper limit of normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =< 5.0 x
ULN
• For patients who will be assigned to Cohort 2 (fulvestrant-resistant), a left
ventricular ejection fraction (LVEF) assessment must be performed within 12 weeks
prior to registration. The LVEF must be >= 50% regardless of the cardiac imaging
facility's lower limit of normal. (LVEF assessment performed by echocardiogram is
preferred; however, MUGA scan may be substituted based on institutional/situational
preferences)
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of registration are eligible for
this trial
• ELIGIBILITY CRITERIA FOR COHORT 1, TREATMENT REGIMEN 2 PATIENTS WHO MIGRATE TO COHORT
2: Cohort migration: Patients treated with control treatment fulvestrant who
experience disease progression may be eligible to migrate to Cohort 2 and receive
combination treatment with binimetinib and fulvestrant. Patients who choose to do so
must meet laboratory values and performance status requirements below and should begin
treatment within 28 days
• PATIENTS WHO MIGRATE TO COHORT 2: Patient's willingness to migrate to Cohort 2
affirmed
• PATIENTS WHO MIGRATE TO COHORT 2: The patient must have an ECOG performance status of
0-2
• PATIENTS WHO MIGRATE TO COHORT 2: Absolute neutrophil count >= 1,500/mm^3
• PATIENTS WHO MIGRATE TO COHORT 2: Platelet count >= 100,000/ mm^3
• PATIENTS WHO MIGRATE TO COHORT 2: Hemoglobin level >= 10 g/dL
• PATIENTS WHO MIGRATE TO COHORT 2: Total bilirubin level =< institutional upper limit
of normal (ULN)
• PATIENTS WHO MIGRATE TO COHORT 2: AST and ALT must be =< 5.0 x ULN
• PATIENTS WHO MIGRATE TO COHORT 2: Creatinine clearance (CrCL) of ≥30 mL/min by the
Cockcroft-Gault formula
• PATIENTS WHO MIGRATE TO COHORT 2: A LVEF performed within the last 3 months must be >=
50% regardless of the cardiac imaging facility's lower limit of normal (LVEF
assessment performed by echocardiogram is preferred; however, MUGA scan may be
substituted based on institutional/situational preferences)
• PATIENTS WHO MIGRATE TO COHORT 2: Pregnancy test according to institutional standards
must be negative (for patients of childbearing potential only)
Exclusion Criteria:
• Concurrent anticancer therapy
• Active autoimmune disease requiring systemic treatment within the past 3 months,
documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic steroids or immunosuppressive agents
• Active brain metastasis. Brain metastases that have been stable for at least 1 month
after completion of treatment are not an exclusion criterion
• History of or evidence of retinal pathology on ophthalmologic examination that is
considered a risk factor for neurosensory retinal detachment/central serous,
chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular
degeneration
• Patients will be excluded if they currently have the following risk factors for RVO
that are documented prior to the enrollment:
• Known uncontrolled glaucoma with intra-ocular pressures >= 21 mmHg
• Known serum cholesterol >= grade 2.
• Known hypertriglyceridemia >= grade 2
• Known hyperglycemia (fasting) >= grade 2
• Patients with baseline QT corrected for heart rate (QTc) > 500 ms, either induced by
medication or congenital long QT syndrome will be excluded due to known side effects
of binimetinib
• Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral
sensory neuropathy) >= grade 2
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
• Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the patient at high risk from treatment
complications
• Other conditions that, in the opinion of the investigator, would preclude the patient
from meeting the study requirements or interfere with interpretation of study results
• Pregnancy or lactation at the time of registration or intention to become pregnant
during the study (Note: Pregnancy testing according to institutional standards for
patients of childbearing potential)
• For binimetinib, highly effective contraception should be used for at least 30
days after the last dose, and patients should not breastfeed for 3 days after the
last dose
• For fulvestrant, highly effective contraception should be used for 1 year after
the last dose, and patients should not breastfeed for 1 year after the last dose
• Use of any investigational product within 30 days prior to study entry
• INELIGIBILITY CRITERIA FOR COHORT 1, TREATMENT REGIMEN 2 PATIENTS WHO MIGRATE TO
COHORT 2
• PATIENTS WHO MIGRATE TO COHORT 2: Not a candidate for binimetinib in the opinion of
the treating investigator
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Negative Breast Carcinoma, Metastatic Hormone Receptor-Positive Breast Carcinoma, Breast
Study of EO-3021 in Adult Patients With Solid Tumors Likely to Express CLDN18.2
This study is an open-label, international, multi-center, Phase 1 study in adult patients
with solid tumors likely to express CLDN18.2.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05980416
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Key
Inclusion Criteria:
• Availability of tumor tissue (archived and fresh tumor biopsy, if medically feasible)
• Select advanced or metastatic solid tumor that is likely to express CLDN18.2 such as
gastric/GEJ, pancreatic and esophageal cancer
• ≥ 18 years of age
• ECOG performance status (PS) 0 or 1 at Screening
• Progressed on or after standard therapy, or are intolerable for available standard
therapy, or there is no available standard therapy
• Have at least one measurable extra-cranial lesion as defined by RECIST v1.1
• Adequate organ function
• Life expectancy > 12 weeks
• Ability to understand the nature of this study, comply with protocol requirements, and
give written informed consent
• Willingness of men and women of reproductive potential to observe conventional and
effective birth control for the duration of treatment and for 3 months following study
completion
Key
Exclusion Criteria:
• Pregnant or breastfeeding
• Symptomatic or untreated brain metastases
• Have previously received CLDN18.2 antibody drug conjugates (ADCs) or any ADC
containing an auristatin payload (prior monoclonal antibody against CLDN18.2 may be
eligible)
• Have peripheral neuropathy Grade ≥2
• Have history of non-infectious pneumonitis/interstitial lung disease
• Have diagnosis of another malignancy, or history of systemic treatment for invasive
cancer within last 3 years. Note: Patients with Stage I cancer who have received
definitive local treatment and are considered unlikely to recur are eligible.
Diagnosis of non-melanoma skin cancer, carcinoma in situ of the cervix or breast, or
noninvasive tumor does not affect eligibility
• Have active ocular surface disease at baseline (based on screening ophthalmic
examination)
• Have serious concurrent illness or clinically relevant active bacterial, fungal or
viral infection
• Have previous hypersensitivity to any known components of EO-3021 or history of severe
infusion reaction or hypersensitivity (CTCAE Grade 3 or higher) with monoclonal
antibody treatment
• Clinically significant cardiac disease, including but not limited to symptomatic
congestive heart failure, unstable angina, acute myocardial infarction within 6 months
of planned first dose, or unstable cardiac arrhythmia requiring therapy (including
torsades de pointes)
• Have history of allogenic hematopoietic stem cell transplantation or solid organ
transplantation with ongoing systemic immunosuppressive therapy
• Patients who are not appropriate candidates for participation in this clinical study
for any other reason as deemed by the Investigator
Pancreas Neoplasm, Stomach Neoplasm, Gastrointestinal Neoplasms, Digestive System Neoplasm, Neoplasms by Site, Neoplasms, Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010)
The purpose of this study is to assess the safety and tolerability and to confirm the dose of
nemtabrutinib in combination with venetoclax in participants with R/R CLL/SLL. The primary
study hypotheses are that the combination of nemtabrutinib plus venetoclax is superior to VR
with respect to progression-free survival (PFS) per 2018 International Workshop on Chronic
Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded independent central review
(BICR).
Christopher Fletcher, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05947851
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Inclusion Criteria:
• Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL) and active disease clearly documented to initiate therapy.
• Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, immunoglobulin
heavy chain gene (IGHV) mutation status and Bruton's tyrosine kinase (BTK)-C481
mutation status results required before randomization for Part 2 participants only.
• Relapsed or refractory to at least 1 prior available therapy.
• Have at least 1 marker of disease burden.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7
days before randomization.
• Has a life expectancy of at least 3 months.
• Has the ability to swallow and retain oral medication.
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they
have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have
undetectable HBV deoxyribonucleic acid (DNA) viral load before randomization.
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV
ribonucleic acid (RNA) viral load is undetectable at screening.
• Participants with human immunodeficiency virus (HIV) who meet ALL eligibility
criteria.
• Participants with adequate organ function with specimens collected within 7 days
before the start of study intervention.
• If capable of producing sperm, participant agrees to eliminate Nemtabrutinib: 12 days,
Venetoclax: 1 month (30 days), Rituximab (rituximab biosimilar): not applicable;
abstains from penile-vaginal intercourse as their preferred and usual lifestyle; OR
uses prescribed contraception.
• Participant assigned female sex at birth are eligible to participate if not pregnant
or breastfeeding and are not a person of childbearing potential (POCBP) OR is a POCBP
and uses a contraceptive method that is highly effective, has a negative highly
sensitive pregnancy test, and abstains from breastfeeding.
Exclusion Criteria:
• Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
• Has gastrointestinal (GI) dysfunction that may affect drug absorption.
• Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years.
• Has diagnosis of Richter Transformation or active central nervous system (CNS)
involvement by CLL/SLL.
• Has an active infection requiring systemic therapy, such as intravenous (IV)
antibiotics, during screening.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric
Castleman's Disease and/or acquired immune deficiency syndrome (AIDS)-defining
opportunistic infection in the past 12 months before screening.
• Has QT interval corrected (QTc) prolongation or other significant electrocardiogram
(ECG) abnormalities.
• Has a known allergy/sensitivity to nemtabrutinib or contraindication to
venetoclax/rituximab (or rituximab biosimilar), or any of the excipients.
• Has history of severe bleeding disorders (eg, hemophilia).
• Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if
prior therapy was a monoclonal antibody) before randomization.
• Has received prior B-cell lymphoma 2 inhibitor(s) (BCL2i) including venetoclax or
Non-covalent Bruton's tyrosine kinase inhibitor (BTKi).
• Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow
therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A
strong inhibitors.
• Has received a live or live attenuated vaccine within 30 days before the first dose of
study intervention.
• Has received an investigational agent or has used an investigational device within 4
weeks before study intervention administration.
• Has a known psychiatric or substance use disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
• Participants who have not adequately recovered from major surgery or have ongoing
surgical complications.
A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors
The purpose of this study is to characterize the safety, tolerability, and efficacy of
IDE161.
Mark Burkard, MD, PhD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05787587
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Inclusion Criteria:
1. Adult participants must be 18 years of age or older
2. Advanced or metastatic solid tumors excluding primary central nervous system (CNS)
tumors
3. Have documented evidence of genetic alterations conferring homologous recombination
deficiency
4. Participant must have progressed on at least one prior line of therapy in the advanced
or metastatic setting that is considered an appropriate standard of care, or for which
the participant has documented intolerance
Exclusion Criteria:
1. Known primary CNS malignancy
2. Impairment of GI function or GI disease that may significantly alter the absorption of
IDE161
3. Have active, uncontrolled infection
4. Clinically significant cardiac abnormalities
5. Major surgery within 4 weeks prior to enrollment
6. Radiation therapy within 2 weeks prior to enrollment
7. Systemic cytotoxic chemotherapy within 4 weeks prior to enrollment
8. Radioimmunotherapy within 6 weeks of enrollment
9. Treatment with a therapeutic antibody within 4 weeks prior to enrollment
10. Treatment with an anti-cancer small molecule within 5 half-lives (t1/2), or 2 weeks,
whichever is shorter
Advanced or Metastatic Solid Tumors, Breast Cancer, Ovarian Cancer, Pancreas Cancer, Prostate Cancer, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
Testing the Safety of the Anti-Cancer Drugs Durvalumab and Olaparib During Radiation Therapy for Locally Advanced Unresectable Pancreatic Cancer
This phase I trial tests the safety and tolerability of olaparib in combination with
durvalumab and radiation therapy in patients with pancreatic cancer that has spread to nearby
tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable).
Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA)
when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their
damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy.
Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune
system attack the cancer, and may interfere with the ability of tumor cells to grow and
spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill
cancer cells and shrink tumors. The combination of targeted therapy with olaparib,
immunotherapy with durvalumab and radiation therapy may stimulate an anti-tumor immune
response and promote tumor control in locally advanced unresectable pancreatic cancer.
Jeremy Kratz, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05411094
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Inclusion Criteria:
• Patients must have histologically confirmed pancreatic cancer (excluding islets) not
otherwise specified (NOS) (Medical Dictionary for Regulatory Activities [MEDDRA] code:
10033612).
• Patients must have unresectable locally advanced pancreatic cancer as determined by a
multidisciplinary tumor board applying National Comprehensive Cancer Network (NCCN)
version (v)2.2021 criteria or as surgically determined during failed resection
attempt.
• Patients must have had prior first-line chemotherapy for this cancer for at least 16
weeks without clinical, biochemical, or radiologic progression. There should be a
washout of at least 2 weeks from first-line chemotherapy and start of therapy on
clinical trial.
• Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of durvalumab and olaparib in combination with radiation in patients < 18
years of age, children are excluded from this study.
• Body weight >30 kg.
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%).
• Hemoglobin >= 9.0 g/dL without blood transfusion in last 4 weeks (within 2 weeks of
enrollment).
• Absolute neutrophil count >= 1,500/mcL (within 2 weeks of enrollment).
• Platelets >= 100,000/mcL (within 2 weeks of enrollment).
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 2 weeks of
enrollment).
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine transferase (ALT) (serum glutamic pyruvic transaminase) [SGPT]) =< 2.5
x institutional ULN (within 2 weeks of enrollment).
• Creatinine =< 1.5 x institutional ULN (within 2 weeks of enrollment).
• Measured creatinine clearance > 60 mL/min/1.73 m^2 (within 2 weeks of enrollment).
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
• Women < 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy).
• Women >= 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses > 1 year ago, had
chemotherapy-induced menopause with last menses > 1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
hysterectomy).
• Life expectancy >= 16 weeks.
• Patients who are human immunodeficiency virus (HIV) positive may participate IF they
meet the following eligibility requirements:
• They must be stable on their anti-retroviral regimen with evidence of at least
two undetectable viral loads within the past 6 months on the same regimen; the
most recent undetectable viral load must be within the past 12 weeks.
• They must have a CD4 count of greater than 250 cells/mcL over the past 6 months
on this same anti-retroviral regimen and must not have had a CD4 count < 200
cells/mcL over the past 2 years, unless it was deemed related to the cancer
and/or chemotherapy induced bone marrow suppression.
• For patients who have received chemotherapy in the past 6 months, a CD4
count < 250 cells/mcL during chemotherapy is permitted as long as viral
loads were undetectable during this same chemotherapy.
• They must have an undetectable viral load and a CD4 count >= 250 cells/mcL within
7 days of enrollment.
• They must not be currently receiving prophylactic therapy for an opportunistic
infection and must not have had an opportunistic infection within the past 6
months.
• HIV-infected patients should be monitored every 12 weeks for viral load and CD4
counts.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated. Patients with a past
or resolved HBV infection (defined as the presence of hepatitis B core antibody
[anti-HBc] and absence of hepatitis B surface antigen [HbsAg]) are eligible.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load. Patients positive for HCV
antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV
ribonucleic acid (RNA).
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial.
• Willing to provide archived tissue, if available, from a previous biopsy. If tissue
from initial biopsy is not available, a repeat biopsy is NOT required and patient will
be eligible for enrollment.
• Patients must have radiographically measurable or evaluable disease (as per Response
Evaluation Criteria in Solid Tumors [RECIST]v1.1).
• Must be able to tolerate computed tomography (CT) and/or magnetic resonance imaging
(MRI) with contrast.
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should behave a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better.
• The effects of durvalumab and olaparib on the developing human fetus are unknown. For
this reason and because radiotherapy used in this trial is known to be teratogenic,
women of child-bearing potential and men must agree to use adequate contraception
prior to study entry, for the duration of study participation, and for 6 months after
the last dose of study treatment. Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately. Male patients should not donate sperm throughout
the period of taking olaparib and for 6 months following the last dose of olaparib.
All females of childbearing potential (not surgically sterilized, and between menarche
and 1 year post menopause) must have a negative screening pregnancy test.
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity who have a legally-authorized
representative (LAR) and/or family member available will also be eligible.
Exclusion Criteria:
• Patients who have had prior upper abdominal radiotherapy prior to entering the study.
• Patients who have not recovered from grade >= 2 AEs due to prior anti-cancer therapy
with the exception of alopecia, vitiligo, and the laboratory values defined in the
inclusion criteria.
• Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab may be included only after consultation with the Study
Physician.
• Major surgical procedure within 28 days prior to enrollment. Note: Local surgery of
isolated lesions for palliative intent is acceptable. Laparoscopy and/or laparotomy
without resection does not constitute a major surgical procedure.
• Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
• Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of
prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
• Receipt of live attenuated vaccine within 30 of planned start of study therapy. Note:
Patients, if enrolled, should not receive live vaccine whilst receiving
investigational product (IP) and up to 30 days after the last dose of IP.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to olaparib or durvalumab.
• Patients with any other significant condition(s) that would make this protocol
unreasonably hazardous
• Patients receiving any medications or substances that are inhibitors or inducers of
CYP3A4/5 are ineligible. Because the lists of these agents are constantly changing, it
is important to regularly consult a frequently-updated medical reference. As part of
the enrollment/informed consent procedures, the patient will be counseled on the risk
of interactions with other agents, and what to do if new medications need to be
prescribed or if the patient is considering a new over-the-counter medicine or herbal
product. The required washout period prior to starting olaparib is 5 weeks for
enzalutamide or phenobarbital, and 3 weeks for other agents.
• Must not have prior history of organ transplantation, allogeneic transplantation, or
double umbilical cord transplantation.
• Must not have germline BRCA1 or BRCA2 mutation.
• Prisoners or subjects who are involuntarily incarcerated, or compulsorily detained for
treatment of either a psychiatric or physical (e.g. infectious disease) illness would
be excluded.
• Patients must not have previously received anti-PD-1/PD-L1 antibodies or PARP
inhibitor for treatment of this cancer.
• Patients must not have myelodysplastic syndrome/acute myeloid leukemia or features
suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).
• Pregnant women are excluded from this study because olaparib is a small molecule agent
with the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with olaparib, breastfeeding should be discontinued if the
mother is treated with olaparib. These potential risks may also apply to other agents
used in this study.
• Participants must not have an active, known or suspected autoimmune disease which may
affect vital organ function or has/may require systemic immunosuppressive therapy for
management. Participants with inflammatory disorders (including inflammatory bowel
disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of
diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener
syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,
hypophysitis, uveitis, etc.]) are also excluded with the exception of the following:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on
hormone replacement.
• Any chronic skin condition that does not require systemic therapy.
• Patients without active disease in the last 5 years may be included but only
after consultation with the study physician.
• Patients with celiac disease controlled by diet alone.
• Participants with type I diabetes mellitus, hypothyroidism only requiring hormone
replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not
requiring systemic treatment, or conditions not expected to recur in the absence
of an external trigger (such as celiac disease controlled by diet) are permitted
to enroll. Patients without active disease for 5 years may also be enrolled after
consultation with the study monitor or sponsor.
• Patients must not have serious, uncontrolled medical disorder, non-malignant systemic
disease. Examples include but are not limited to active heart disease including
symptomatic heart failure (New York Heart Association [NYHA] class 3 or 4), unstable
angina pectoris, uncontrolled cardiac arrhythmia or interstitial lung disease,
uncontrolled major seizure disorder, unstable spinal cord compression, superior vena
cava syndrome, extensive interstitial bilateral lung disease on high resolution
computed tomography (HRCT) scan.
• Must not have known active inflammatory gastrointestinal disease, chronic diarrhea
(other than exocrine insufficiency controlled by enzyme replacement therapy), short
gut syndrome, or other conditions that would limit the absorption of the study drug.
Patient must be able to swallow and retain an oral medication.
• Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis [TB] testing
in line with local practice), hepatitis B (known positive HBV surface antigen (HbsAg)
result), or hepatitis C.
• In addition, the patient must not have resting electrocardiogram (ECG) indicating
uncontrolled, potentially reversible cardiac conditions, as judged by the investigator
(e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart
failure, corrected QT interval by Fredericia (QTcF) prolongation > 500 ms, electrolyte
disturbances, etc.), or patients with congenital long QT syndrome.
Locally Advanced Pancreatic Carcinoma, Stage II Pancreatic Cancer AJCC v8, Stage III Pancreatic Cancer AJCC v8, Unresectable Pancreatic Carcinoma, Pancreas
Correlating Early FDG PET/CT and ctDNA in Immune Checkpoint Inhibitor (ICI)-Treated Melanoma Patients
The purpose of this research study is to determine if analysis of PET/CT scans and testing of
blood samples in people with melanoma that has spread in their body can help researchers
determine which patients are more or less likely to respond to immunotherapy and are more or
less likely to have side effects. 24 participants will be enrolled and be on study until
approximately 4 weeks after their first dose of Immune Checkpoint Inhibitor therapy.
Vincent Ma, MD
All
18 Years and over
IV
This study is NOT accepting healthy volunteers
NCT06199713
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Inclusion Criteria:
• Willing to provide informed consent.
• Must have an advanced stage III or stage IV melanoma diagnosis for which treatment
with ipilimumab, nivolumab, and/or pembrolizumab, either alone or in combination with
other ICI therapy, is planned.
• Must be planning to participate in Signatera™ (ctDNA level) monitoring with standard
of care laboratory testing routinely obtained for treatment with ICI therapy.
• Individuals at least 18 years of age.
• Women of childbearing potential must be willing to use effective contraception as
discussed with their oncologist while participating in this study.
• Willing to comply with all study procedures and be available for the duration of the
study.
Exclusion Criteria:
• Not able to receive treatment with ICI therapy
• Use of investigational drugs, biologics, or devices within 30 days prior to
enrollment.
• Women who are pregnant, lactating, or planning on becoming pregnant during the study.
• Not suitable for study participation due to other reasons at the discretion of the
investigators.
Melanoma, Skin, Other Skin, Melanoma/Skin cancer, Melanoma, Melanoma Stage III, Melanoma Stage IV, Unresectable Melanoma
This pilot comparative effectiveness trial will compare two active smoking cessation
treatments in terms of effectiveness, equity across patient subpopulations, and efficiency
among adult patients diagnosed with cancer within the past 3 years. An enhanced treatment
comprising 12 weeks of varenicline treatment and 7 smoking cessation coaching calls with a
cancer focus will be compared against an active comparator modeled after standard quitline
treatments (2 weeks of nicotine patch therapy with 3 phone coaching calls). Approximately 50
participants will be recruited to generate estimates of the effects, acceptability, costs,
and equity of enhanced treatment (vs. standard treatment), with the primary outcome being
abstinence from smoking 26 weeks after trying to quit.
Danielle Mccarthy
All
18 Years and over
Phase 4
This study is NOT accepting healthy volunteers
NCT06218823
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Inclusion Criteria:
• Alive (per medical record)
• Diagnosed with cancer in the past 3 years
• Received care from a participating oncology clinic in the past year
• Has a current tobacco use status
• Does not have a preferred language other than English (missing language preference
will be included).
• Valid address that is not a correctional facility or residential treatment/care
facility.
• No flag for patient cognitive impairment, activated health care power of attorney, or
other health care agent (e.g., legally authorized representative) in the EHR.
The following additional inclusion criteria must be met for inclusion in the CET
• Smoked combustible cigarettes in the past month.
• Able to speak and understand English.
• Willing to set a date to quit smoking in the next 60 days.
• Willing to receive smoking treatment information.
• Willing to complete study activities.
Exclusion Criteria:
• No current suicidal ideation.
• Suicide attempt in the past year.
• Currently receiving treatment for bipolar disorder, schizophrenia, schizoaffective
disorder, or psychotic disorder.
• Incarceration.
• Unable to provide informed consent to treatment (i.e., cannot answer questions about
study procedures or risks after hearing about the study).
Smoking Cessation, Cancer, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
A Phase 1/2 Study of DCC-3116 in Patients With RAS/MAPK Pathway Mutant Solid Tumors
This is a Phase 1/2, multicenter, open label, first in human (FIH) study of DCC-3116 as
monotherapy, and in combination with trametinib, binimetinib, or sotorasib in patients with
advanced or metastatic solid tumors with RAS/MAPK pathway mutation. The study consists of 2
parts, a dose-escalation phase, and an expansion phase.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04892017
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Inclusion Criteria:
1. Male or female participants ≥18 years of age
2. Dose Escalation Phase (Part 1):
Escalation Cohort B combination with trametinib and Cohort C combination with
binimetinib closed on January 8, 2024.
1. Participants must have a pathologically confirmed diagnosis of an advanced or
metastatic solid tumor with a documented RAS, NF1, or RAF mutations. A molecular
pathology report documenting mutational status of RAS, NF1, or RAF must be
available.
2. Progressed despite standard therapies, and received at least 1 prior line of
anticancer therapy.
• Participants with a documented mutation in BRAF V600E or V600K must have
received approved treatments known to provide clinical benefit prior to
study entry.
3. Participants enrolled in the DCC-3116 and sotorasib cohort (Cohort D) must have a
KRAS G12C mutation.
3. Dose Expansion Phase (Part 2):
Expansion Cohorts 1, 2, 3 and 4 combinations will not open for enrollment.
Cohort 5: Patients with KRAS G12C mutant NSCLC
• Pathologically confirmed NSCLC with a documented mutation in KRAS G12C.
• Received at least 1 prior line but no more than 3 prior lines of systemic therapy
in the advanced or metastatic setting.
• Have not received prior sotorasib or other KRAS G12C inhibitor therapy.
4. Must provide a fresh tumor biopsy from a primary or metastatic cancer lesion that can
be biopsied with acceptable risk as determined by the Investigator, and archival tumor
tissue sample, if available. If a fresh tumor biopsy is not possible, then an archival
tumor tissue sample must be provided.
5. Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 (Dose Escalation) or 0 to 1
(Dose Expansion) at Screening
6. Adequate organ function and bone marrow function.
7. If a female of childbearing potential must have a negative pregnancy test prior to
enrollment and agree to follow the contraception requirements.
8. Male participants must agree to follow contraception requirements.
9. Must provide signed consent to participate in the study and is willing to comply with
study-specific procedures.
Exclusion Criteria:
1. Must not have received the following within the specified time periods prior to the
first dose of study drug:
1. Prior therapies (anticancer or therapies given for other reasons) that are known
strong or moderate inhibitors or inducers of CYP3A4 or P-gp including certain
herbal medications (e.g., St. John's Wort): 14 days or 5× the half-life of the
medication (whichever is longer)
2. All other prior anticancer therapies or any therapy that is investigational for
the participant's condition with a known safety and PK profile: 14 days or 5× the
half-life of the medication (whichever is shorter)
3. Investigational therapies with unknown safety and PK profile: 28 days. If there
is enough data on the investigational therapy to assess the risk for drug-drug
interactions and late toxicities of prior therapy as low, the Sponsor's Medical
Monitor may approve a shorter washout of 14 days
4. Grapefruit or grapefruit juice: 14 days
2. Have not recovered from all toxicities from prior therapy according to National Cancer
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
3. Presence or history of central nervous system (CNS) metastases or leptomeningeal
disease, with some exceptions
4. New York Heart Association Class III or IV heart disease, active ischemia, or any
other uncontrolled cardiac condition such as angina pectoris, clinically significant
cardiac arrhythmia requiring therapy, uncontrolled hypertension, congestive heart
failure, or myocardial infarction within 6 months prior to the first dose of study
drug.
5. Prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on
repeated demonstration of QTcF >450 ms in males or >470 ms in females at screening, or
history of long QT syndrome.
6. Left ventricular ejection fraction (LVEF) <50% at Screening
7. Systemic arterial thrombotic or embolic events within 6 months prior to the first dose
of study drug
8. Systemic venous thrombotic events within 1 month prior to the first dose of study drug
9. Malabsorption syndrome
10. Bone disease that requires ongoing treatment or has required treatment.
11. Major surgery within 4 weeks of the first dose of study drug. All surgical wounds must
be healed and free of infection or dehiscence before the first dose of the study drug.
12. Any other clinically significant comorbidities.
13. For participants receiving DCC-3116 and trametinib combination or DCC-3116 and
binimetinib combination: previous treatment with trametinib or binimetinib that
resulted in treatment discontinuation due to intolerability as a result of an adverse
event (AE) that was considered related to trametinib or binimetinib.
14. For participants receiving DCC-3116 and sotorasib combination in Dose Escalation Part
1: previous treatment with sotorasib that resulted in treatment discontinuation due to
intolerability as a result of an adverse event (AE) that was considered related to
sotorasib.
15. For participants receiving DCC-3116 and sotorasib combination: Use of proton pump
inhibitors (PPIs) and H2 receptor antagonists that cannot be discontinued 3 days prior
to the start of study drug administration.
16. Known allergy or hypersensitivity to any component of the investigational drug
products.
17. Known human immunodeficiency virus unless the following requirements are met:
1. CD4 count >350/µL
2. No AIDS-defining opportunistic infection in the last 12 months
3. Stable anti-retroviral regimen with medications that are not prohibited by the
protocol for at least 4 weeks with HIV viral load less than 400 copies/mL prior
to enrollment.
18. Known active hepatitis B, active hepatitis C infection or if the participant is taking
medications that are prohibited per protocol.
19. If female, the participant is pregnant or lactating.
20. Ongoing participation in an interventional study.
21. For participants receiving DCC-3116 and binimetinib combination: Known Gilbert's
syndrome
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus, Non-Small Cell Lung Cancer, Advanced Solid Tumor, Metastatic Solid Tumor
A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, or 7+3 in Patients With AML
This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic
activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and 7+3
for two different molecularly-defined arms, NPM1-m and KMT2A-r.
Kalyan Nadiminti, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05735184
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Key
Inclusion Criteria:
• Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either
newly diagnosed or relapsed/refractory AML
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Adequate liver, renal, and cardiac function according to protocol defined criteria
• A female of childbearing potential must agree to use adequate contraception from the
time of screening through 180 days following the last dose of study intervention. A
male of childbearing potential must agree to use abstinence or adequate contraception
from the time of screening through 90 days following the last dose of study
intervention
Key
Exclusion Criteria:
• Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic
leukemia
• Known history of BCR-ABL alteration
• Advanced malignant hepatic tumor [for patients receiving ven/aza combination]
• Administration of live attenuated vaccines within 14 days prior to, during, or after
treatment until B-cell recovery
• Active central nervous system (CNS) involvement by AML.
• Clinical signs/symptoms of leukostasis or WBC > 25,000 / microliter. Hydroxyurea
and/or leukapheresis are permitted to meet this criterion
• Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except
for alopecia
• Known clinically active human immunodeficiency virus, active hepatitis B or active
hepatitis C infection
• For newly diagnosed cohorts: received prior chemotherapy for leukemia, except
hydroxyurea and/or leukapheresis to control leukocytosis, prior treatment with
all-transretinoic acid for initially suspected acute promyelocytic leukemia, or
non-HMA therapy for prior myelodysplastic syndrome
• For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy,
or any ancillary therapy that is considered to be investigational < 14 days prior to
the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of
study drug
• Uncontrolled intercurrent illness including, but not limited to, cardiac illness as
defined in the protocol
• Mean corrected QT interval corrected for heart rate by Fredericia's formula (QTcF)
>480 ms on triplicate ECGs
• Uncontrolled infection
• Women who are pregnant or lactating
• An active malignancy and currently receiving chemotherapy for that malignancy or
disease that is uncontrolled/progressing
Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25 (OFSET)
This Phase III Trial will determine whether adjuvant chemotherapy (ACT) added to ovarian
function suppression (OFS) plus endocrine therapy (ET) is superior to OFS plus ET in
improving invasive breast cancer-free survival (IBCFS) among premenopausal, early- stage
breast cancer (EBC) patients with estrogen receptor (ER)-positive, HER2-negative tumors and
21-gene recurrence score (RS) between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).
Malinda West, MD
Female
18 Years to 60 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05879926
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Inclusion Criteria:
• A patient cannot be considered eligible for this study unless ALL of the following
conditions are met.
• The patient or a legally authorized representative must provide study-specific
informed consent prior to pre-entry and, for patients treated in the U.S.,
authorization permitting release of personal health information.
• Female patients must be greater than or equal to 18 years of age.
• Patients must be premenopausal (evidence of functioning ovaries) at the time of
pre-entry. For study purposes, premenopausal is defined as:
• Age 50 years or under with spontaneous menses within 12 months; or
• Age greater than 50-60 years with spontaneous menses within 12 months plus
follicle-stimulating hormone (FSH) and estradiol levels in the premenopausal
range; or
• Patients with amenorrhea due to IUD or prior uterine ablation must have FSH and
estradiol levels in the premenopausal range; or
• Patients with prior hysterectomy must have FSH and estradiol levels in the
premenopausal range.
• The patient must have an ECOG performance status of less than or equal to 2 (or
Karnofsky greater than or equal to 60%).
• Patients may have ipsilateral or contralateral synchronous breast cancer if the
highest stage tumor meets entry criteria, and the other sites of disease would
not require chemotherapy or HER2-directed therapy.
• Patients may have multicentric or multifocal breast cancer if the highest stage
tumor meets entry criteria, and the other sites of disease would not require
chemotherapy or HER2-directed therapy.
• Patient may have undergone a total mastectomy, skin-sparing mastectomy,
nipple-sparing mastectomy, or a lumpectomy.
• For patients who undergo a lumpectomy, the margins of the resected specimen or
re-excision must be histologically free of invasive tumor and DCIS (ductal
carcinoma in situ) with no ink on tumor as determined by the local pathologist.
If pathologic examination demonstrates tumor at the line of resection, additional
excisions may be performed to obtain clear margins. Positive posterior margin is
allowed if surgeon deems no further resection possible. (Patients with margins
positive for LCIS (lobular carcinoma in situ) are eligible without additional
resection.)
• For patients who undergo mastectomy, the margins must be free of residual gross
tumor. (Patients with microscopic positive margins are eligible if
post-mastectomy RT (radiation therapy) of the chest wall will be administered.)
• Patient must have undergone axillary staging with sentinel node biopsy (SNB),
targeted axillary dissection (TAD), or axillary lymph node dissection (ALND).
• The following staging criteria must be met postoperatively according to AJCC 8th
edition criteria:
• By pathologic evaluation, primary tumor must be pT1-3. (If N0, must be T1c or
higher.)
• By pathologic evaluation, ipsilateral nodes must be pN0 or pN1 (pN1mi, pN1a,
pN1b, pN1c).
• Patients with positive isolated tumor cells (ITCs) in axillary nodes will be
considered N0 for eligibility purposes.
• Patients with micrometastatic nodal involvement (0.2-2 mm) will be considered N1.
• Oncotype DX RS (recurrence score) requirements*:
• If node-negative:
• Oncotype DX RS must be RS 21-25, or
• Oncotype DX RS must be 16-20 and disease must be high clinical risk, defined as:
low histologic grade with primary tumor size greater than 3 cm, intermediate
histologic grade with primary tumor size greater than 2 cm, or high histologic
grade with primary tumor size greater than 1 cm.
• If 1-3 nodes involved:
• Oncotype DX RS must be less than 26.
* Patients with a "Low Risk" or "MP1" MammaPrint (a genomic test that analyzes
the activity of certain genes in early-stage breast cancer) result must have
eligibility assessed with an Oncotype DX RS at pre-entry (see Section 3.1).
Blocks or unstained slides must be sent to the Genomic Health centralized
laboratory for testing at no cost to these patients. If MammaPrint High Risk or
MP2, these patients are not eligible.
• The tumor must be ER and/or PgR-positive (progesterone receptor) by current
ASCO/CAP guidelines based on local testing results. Patients with greater than or
equal to 1% ER and/or PgR staining by IHC will be classified as positive.
• The tumor must be HER2-negative by current ASCO/CAP (American Society of Clinical
Oncology/College of American Pathologists) guidelines based on local testing
results.
• The interval between the last surgery for breast cancer (including re-excision of
margins) and pre-entry must be no more than 16 weeks.
• Short course of endocrine therapy of less than 6 weeks duration before pre-entry
is acceptable either as neoadjuvant or adjuvant therapy. An Oncotype DX RS must
be performed on core biopsy specimen obtained prior to initiation of neoadjuvant
endocrine therapy if received.
• Patients with a prior or concurrent non-breast malignancy whose natural history
or treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible for this trial. This would
include prior cancers treated with curative intent.
• HIV-infected patients on effective anti-retroviral therapy with undetectable
viral load within 6 months are eligible for this trial.
• Radiation therapy should be used according to standard guidelines; the intended
radiation therapy should be declared prior to pre-entry.
Exclusion Criteria:
• • Definitive clinical or radiologic evidence of metastatic disease.
• pT4 (pathological state) tumors, including inflammatory breast cancer.
• History of ipsilateral or contralateral invasive breast cancer. (Patients with
synchronous and/or previous DCIS or LCIS are eligible.)
• If prior ipsilateral DCIS was treated with lumpectomy and XRT (ionizing radiation
therapy), a mastectomy must have been performed for the current cancer.
• Life expectancy of less than 10 years due to co-morbid conditions in the opinion
of the investigator.
Known results from most recent lab studies obtained as part of routine care prior to study
entry showing ANY of the following values:
• ANC (absolute neutrophil count) less than 1200/mm3;
• Platelet count less than 100,000/mm3;
• Hemoglobin less than 10 g/dL;
• Total bilirubin greater than ULN (upper limit of normal) for the lab or greater than
1.5 x ULN for patients who have a bilirubin elevation due to Gilbert's disease or
similar syndrome involving slow conjugation of bilirubin;
• AST(aspartate aminotransferase)(SGOT)/ALT (alanine transminase)(SGPT): greater than 3
× institutional ULN;
• Renal function of GFR (glomular filtration rate) less than 30 mL/min/1.73m2.
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Any treatment with radiation therapy, chemotherapy, or biotherapy administered for the
currently diagnosed breast cancer prior to pre-entry. (Patients with prior ET of more
than 6 weeks duration for treatment of this cancer are not eligible.) Prior tamoxifen
given for breast cancer prevention is allowed. Prior AI or GnRH for fertility
preservation is allowed.
• Hormonally based contraceptive measures must be discontinued prior to pre-entry
(including progestin/progesterone IUDs).
• Patients with evidence of chronic hepatitis B virus (HBV) infection are ineligible
unless the HBV viral load is undetectable on suppressive therapy. Patients with a
history of hepatitis C virus (HCV) infection are ineligible unless they have been
treated and cured or have an undetectable HCV viral load if still on active therapy.
• Pregnancy or lactation at the time of pre-entry. (Note: Pregnancy testing according to
institutional standards for women of childbearing potential must be performed within 2
weeks prior to pre-entry.)
• Other conditions that, in the opinion of the investigator, would preclude the patient
from meeting the study requirements or interfere with interpretation of study results.
Testing the Addition of High Dose, Targeted Radiation to the Usual Treatment for Locally-Advanced Inoperable Non-small Cell Lung Cancer
This phase III trial compares the effect of adding stereotactic body radiation therapy (SBRT)
to standard treatment (image guided radiation therapy [IGRT] and chemotherapy followed by
immunotherapy with durvalumab) versus standard treatment alone in treating patients with
non-small cell lung cancer that cannot be treated by surgery (inoperable). SBRT uses special
equipment to position a patient and deliver radiation to tumors with high precision. This
method may kill tumor cells with fewer doses over a shorter period and cause less damage to
normal tissue. IGRT is a type of radiation that uses a computer to create picture of the
tumor, to help guide the radiation beam during therapy, making it more accurate and causing
less damage to healthy tissue. Standard chemotherapy used in this trial consists of
combinations of the following drugs: cisplatin, carboplatin, paclitaxel, pemetrexed, and
etoposide. Cisplatin is in a class of medications known as platinum-containing compounds. It
works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of
medications known as platinum-containing compounds. It works in a way similar to the
anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by
killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of
medications called antimicrotubule agents. It works by stopping the growth and spread of
tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents.
It works by blocking the action of a certain substance in the body that may help tumor cells
multiply. Etoposide is in a class of medications known as podophyllotoxin derivatives. It
blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells.
Immunotherapy with durvalumab, may induce changes in body's immune system and may interfere
with the ability of tumor cells to grow and spread. Adding SBRT to the standard treatment of
IGRT with chemotherapy and immunotherapy may be more effective at treating patients with
inoperable non-small cell lung cancer than giving the standard treatment alone.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05624996
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Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of stage II or III
(American Joint Committee on Cancer [AJCC] eighth edition) non-small cell lung cancer
(NSCLC) with known PD-L1 status prior to registration
• Patients must have an identified primary tumor and at least one nodal metastasis
(peribronchial/hilar/intrapulmonary, mediastinal/subcarinal,
supraclavicular/scalene)
• Up to 4 cycles of systemic therapy received prior to registration for the current
study cancer is allowable; any prior chemotherapy for a different cancer is also
permissible
• The patient must be deemed clinically appropriate for curative intent definitive
combined modality therapy, based on the following staging assessments:
• History/physical examination prior to registration;
• Magnetic resonance imaging (MRI) scan of the brain (preferred) or CT scan of the
brain (if available, contrast is preferred for all neuroimaging) prior to
registration;
• CT chest with IV contrast (if contrast is available and unless contraindicated,
such as for abnormal kidney function) prior to registration. PET/CT may be used
if the CT portion is of identical diagnostic quality as achieved in a stand-alone
CT
• No evidence of distant metastases based on FDG PET/CT scan obtain within 60 days of
registration
• Primary tumor =< 7 cm
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Hematologic function (e.g. platelets, leukocytes, hemoglobin) amenable, at the
discretion of the treating physician, to allow for treatment with chemotherapy and
concurrent radiation therapy
• Creatinine clearance >= 25 mL/min by the Cockcroft-Gault (C-G) equation
• Subjects with non-malignant pleural effusion are eligible provided the effusion is not
known or demonstrated to be an exudative effusion
• If a pleural effusion is present, the following criteria must be met to exclude
malignant involvement:
• When pleural fluid is visible on both the CT scan and on a chest x-ray, a
pleuracentesis is required to confirm that the pleural fluid is
cytologically negative;
• Effusions that are minimal (i.e., not visible on chest x-ray) that are too
small to safely tap are eligible
• Medical history consistent with the patient being amenable, at the discretion of the
treating physician, to allow for treating with consolidation immunotherapy. Patients
with known EGFR/ALK mutation at the time of registration are eligible, and these
patients can be treated with consolidation durvalumab or chemotherapy at the
discretion of the treating physician
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen
• Negative pregnancy test =< 14 days prior to registration for participants of
childbearing potential
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields that is determined by the treating physician to impede the
treatment of the study malignancy
• Patients without identifiable primary tumor and at least 1 pathologically enlarged
lymph node are not eligible (T3-4N0 or T0N1-3 patients are not eligible). At least 1
radiographically-involved lymph node is required, but pathologic confirmation of
involvement is not mandated
• Centrally located primary tumor < 2 cm from involved nodal disease which would result
in significant overlap of the primary SBRT and nodal radiation fields. Centrally
located is defined as within or touching the zone of the proximal bronchial tree,
which is a volume 2 cm in all directions around the proximal bronchial tree (carina,
right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus,
right middle lobe bronchus, lingular bronchus right and left lower lobe bronchi)
• Participants who are pregnant or unwilling to discontinue nursing
• Participants of childbearing potential (participants who may become pregnant or who
may impregnate a partner) unwilling to use highly effective contraceptives during
therapy and for the Food and Drug Administration (FDA)-labeled contraception timeframe
required after the final dose of the selected chemotherapy regimen, because the
treatment in this study may be significantly teratogenic
Lung, Locally Advanced Lung Non-Small Cell Carcinoma, Stage IIB Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8
Testing Immunotherapy (Atezolizumab) With or Without Chemotherapy in Locoregional MSI-H/dMMR Gastric and Gastroesophageal Junction (GEJ) Cancer
This phase II trial compares atezolizumab in combination with chemotherapy (docetaxel,
oxaliplatin, leucovorin calcium, fluorouracil, capecitabine) to atezolizumab alone for
controlling the growth and/or spreading of the disease in patients with gastric or
gastroesophageal junction (JEG) cancer that has not spread from where it first started
(local) or only has spread to nearby lymph nodes or tissue (locoregional) and has high
microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR). The mismatch repair
(MMR) system in the body corrects errors made during the copying of DNA and serves as a
proofreading function. If this system isn't working correctly, mutations (changes) in DNA
occur which can allow the cancer to grow or spread. This is called dMMR (deficient mismatch
repair) . MSI-H describes cancer cells that have a high number of mutations within
microsatellites. For example, microsatellite testing that shows mutations in 30% or more
microsatellites is called microsatellite instability-high (MSI-H). Microsatellites are short,
repeated sequences of DNA. There is evidence that MSI-H/ dMMR gastric or GEJ tumors respond
well to immunotherapy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may
help the body's immune system attack the cancer, and may interfere with the ability of tumor
cells to grow and spread. Docetaxel is in a class of medications called taxanes. It stops
tumor cells from growing and dividing and may kill them. Oxaliplatin is in a class of
medications called platinum-containing antineoplastic agents. It damages the cell's DNA and
may kill tumor cells. Capecitabine is in a class of medications called antimetabolites. It is
taken up by tumor cells and breaks down into fluorouracil, a substance that kills tumor
cells. Chemotherapy drugs such as leucovorin calcium and fluorouracil work in different ways
to stop the growth of tumor cells, either by killing the cells, by stopping them from
dividing, or by stopping them from spreading. Using atezolizumab as immunotherapy with and
following chemotherapy versus atezolizumab alone prior to and after surgery may shrink or
stabilize the tumor in patients with MSI-H/dMMR localized gastric or GEJ cancer and may
increase the length of time after treatment that cancer does not come back or get worse.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05836584
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patient must be >= 18 years of age
• Patient must have histologically or cytologically confirmed diagnosis of gastric or
gastroesophageal junction adenocarcinoma that is MSI-H/dMMR (microsatellite
instability-high/mismatch repair deficient) as determined by one of three methods:
• Deficient deoxyribonucleic acid (DNA) mismatch repair protein (MMR) expression
status: MMR status must be assessed by immunohistochemistry (IHC) for MMR protein
expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates
dMMR. dMMR may be determined either locally or by site-selected reference lab by
Clinical Laboratory Improvement Act (CLIA)-certified assay
• NOTE: Loss of MLH1 and PMS2 commonly occur together
• Polymerase chain reaction (PCR) determined microsatellite instability
• MSI-H tumor status determined by next-generation sequencing
• Patient must have previously untreated localized gastric, or Siewert type II or III
GEJ (gastroesophageal junction) adenocarcinoma. Tumors must be staged as T2 or greater
primary lesion or be any T stage with the presence of positive locoregional lymph
nodes- N+ (clinical nodes) without evidence of metastatic disease
• Siewert type II tumors: tumors located between 1 cm proximal and 2 cm distal to
the GEJ
• Siewert type III tumors: tumors located between 2 and 5 cm distal to GEJ
• Patient must be amenable to surgical resection with therapeutic intent
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 14 days prior to
randomization)
• Platelets >= 100,000/mcL (obtained =< 14 days prior to randomization)
• Hemoglobin >= 9 g/dL (obtained =< 14 days prior to randomization)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin
=< ULN (for patients with total bilirubin > 1.5 x ULN) (obtained =< 14 days prior to
randomization)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]):
x =< 3 institutional ULN (obtained =< 14 days prior to randomization)
• Creatinine =< 1.5 x institutional ULN OR glomerular filtration rate (GFR) > 50
mL/min/1.73m^2 (obtained =< 14 days prior to randomization)
• Albumin >= 2.5 g/dL (obtained =< 14 days prior to randomization)
• International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN (unless
patient is receiving anticoagulant therapy as long as PT or partial thromboplastin
time [PTT] is within therapeutic range of intended use of anticoagulants) (obtained =<
14 days prior to randomization)
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (unless patient is receiving
anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
of anticoagulants) (obtained =< 14 days prior to randomization)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• Patient must have no contraindications to receive one of the chemotherapy regimens:
FLOT or mFOLFOX / CAPOX
• Patient must not have had prior potentially curative surgery for carcinoma of the
stomach/GEJ
• Patient must not receive any other standard anti-cancer therapy or experimental agent
concurrently with the study drugs
• Patient must have recovered from clinically significant adverse events of their most
recent therapy/intervention prior to randomization
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patient must have chest/abdomen/pelvis CT completed within 4 weeks prior to
randomization
• Patient may not have received prior treatment with an immune checkpoint inhibitor
(anti-PD-1, anti-PDL-1, anti-PDL-2, anti-CTLA4 monoclonal antibody)
• Patient must not have received any live vaccines within 30 days prior to randomization
and while participating in the study. Live vaccines include, but are not limited to,
the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus
Calmette-Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive
inactivated vaccines and any non-live vaccines including those for the seasonal
influenza and coronavirus disease 2019 (COVID-19) (Note: intranasal influenza
vaccines, such as Flu-Mist [registered trademark] are live attenuated vaccines and are
not allowed). If possible, it is recommended to separate study drug administration
from vaccine administration by about a week (primarily, in order to minimize an
overlap of adverse events)
• Patient must not have active autoimmune disease or history of autoimmune disease that
might recur, which may affect vital organ function or require immune suppressive
treatment including systemic corticosteroids. These include but are not limited to
patients with a history of immune related neurologic disease, multiple sclerosis,
autoimmune (demyelinating) neuropathy, Guillain- Barre syndrome, myasthenia gravis;
systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective
tissue disease, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative
colitis and hepatitis. Patients with a history of toxic epidermal necrolysis (TEN),
Stevens-Johnson syndrome, or phospholipid syndrome are ineligible because of the risk
of recurrence or exacerbation of disease. Patients with vitiligo, endocrine
deficiencies including thyroiditis managed with replacement hormones including
physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other
arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and
patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid
antibodies should be evaluated for the presence of target organ involvement and
potential need for systemic treatment but otherwise are eligible.
• Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus,
residual hypothyroidism due to autoimmune condition only requiring hormone
replacement, psoriasis not requiring systemic treatment, or conditions not
expected to recur in the absence of an external trigger (precipitating event)
• Patients must not be receiving systemic steroid therapy equivalent to > 10 mg
prednisone per day or any other form of immunosuppressive therapy within 7 days prior
to randomization. Topical corticosteroid or occasional inhaled corticosteroids are
allowed
• Patient must not have known interstitial lung disease that is symptomatic or may
interfere with the detection or management of suspected drug-related pulmonary
toxicity, and must not have a known history of prior pneumonitis requiring treatment
with steroids, or any evidence of active, non-infectious pneumonitis
• Patient must not have a known history of active TB (Bacillus Tuberculosis)
• Patient must not have any hypersensitivity to atezolizumab or any of its excipients
• Patient must not have received any prior chemotherapy, targeted small molecule
therapy, or radiation therapy for their MSI-H/dMMR gastric and GEJ cancer
• Patient must not have had an allogeneic bone marrow/stem, cell or solid organ
transplant
• Patient must not have a history or current evidence of any condition (e.g., known
deficiency of the enzyme dihydropyrimidine dehydrogenase [DPD]), therapy, or
laboratory abnormality that might confound the results of the trial, interfere with
the patient's participation for the full duration of the trial, or is not in the best
interest of the patient to participate, in the opinion of the treating investigator
• Patient must not have any condition that would interfere with the cooperation with the
requirements of this trial
• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn
fetus and possible risk for adverse events in nursing infants with the treatment
regimens being used
• All patients of childbearing potential must have a blood test or urine study
within 14 days prior to randomization to rule out pregnancy
• A patient of childbearing potential is defined as anyone, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the
following criteria: 1) has achieved menarche at some point, 2) has not undergone
a hysterectomy or bilateral oophorectomy; or 3) has not been naturally
postmenopausal (amenorrhea following cancer therapy does not rule out
childbearing potential) for at least 24 consecutive months (i.e., has had menses
at any time in the preceding 24 consecutive months)
• Patient must not expect to conceive or father children by using accepted and effective
method(s) of contraception or by abstaining from sexual intercourse while on protocol
treatment. Patients of childbearing potential must continue contraception measures for
5 months after the last dose of atezolizumab and for 9 months after the last dose of
chemotherapy. Male patients with partners of childbearing potential must continue
contraception measures for 6 months after the last dose of chemotherapy. Patients of
childbearing potential must also not breastfeed while on treatment and for 5 months
after the last dose of atezolizumab and for 3 months after the last dose of
chemotherapy
• Patient must have the ability to understand and the willingness to sign a written
informed consent document. Patients with impaired decision-making capacity (IDMC) who
have a legally authorized representative (LAR) or caregiver and/or family member
available will also be considered eligible
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• The investigator must declare the chemotherapy regimen their patient will receive
(FLOT or mFOLFOX / CAPOX) prior to randomization
Clinical Stage I Gastric Cancer AJCC v8, Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage II Gastric Cancer AJCC v8, Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IVA Gastric Cancer AJCC v8, Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Stomach
A Study of Alpelisib and Fulvestrant to Treat Endometrial Cancer
This is a 2 stage multi-center study designed to evaluate the efficacy of the combination of
alpelisib and fulvestrant in patients with PIK3CA-mutated ER-positive endometrioid
endometrial cancers by estimating the objective response rate (ORR). Treatment will continue
until either unacceptable toxicity, progression of disease, or investigator/patient request
for withdrawal.
Janelle Sobecki, MD
Female
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05154487
Show full eligibility criteria
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Inclusion Criteria:
1. Patient must have advanced (FIGO 2014 Stage III or IV), persistent, or recurrent
endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy.
Histologic confirmation of recurrent disease is required. For cases of persistent
disease, histologic confirmation of the primary disease with radiologic evidence of
progression is required.
2. Patients must have endometrioid histology (all grades allowed) based on hysterectomy
or biopsy specimen and have positive expression of ER and oncogenic PIK3CA mutation
per criteria below.
a. PIK3CA mutations considered oncogenic include R88Q, N345K, C420R, E542K, E545X,
Q546X, M1043I, H1047X, or G1049R. The list of oncogenic mutations acceptable for
enrollment may be expanded as further information becomes available.
i. Oncogenic PIK3CA mutations identified on tests performed by the labs listed on
https://ecog-acrin.org/nci-match-eay131-designated-labs will be considered confirmed
for the purposes of this study ii. Oncogenic PIK3CA mutations identified by other
tests will need to be confirmed by the study prior to enrollment b. Estrogen receptor
(ER) status will be considered positive if ≥1% of tumor cells demonstrate positive
nuclear staining by immunohistochemistry. Pathology report documenting ER status must
be provided at enrollment.
Sites are required to report results of previous MMR and/or MSI status testing in
Medidata Rave if available.
3. All patients must have measurable disease. Measurable disease is defined by RECIST
version 1.1. Measurable disease is defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded). Each
lesion must be greater than or equal to 10mm when measured by CT, MRI or caliper
measurement by clinical exam; or greater than or equal to 20mm when measured by chest
x-ray. Lymph nodes must be greater than or equal to 15mm in short axis when measured
by CT or MRI.
Patients must have at least one "target lesion" to be used to assess response on this
protocol as defined by RECIST 1.1. Tumors within a previously irradiated field will be
designated as "non-target" lesions unless progression is documented or a biopsy is
obtained to confirm persistence at least 90 days following completion of radiation
therapy.
4. Prior chemotherapy in the adjuvant setting for Stage I, II, or III is permitted. Prior
chemoradiotherapy for a pelvic recurrence is permitted.
Note: No prior chemotherapy in the setting of Stage IV disease is permitted unless the
patient was without evidence of disease at the completion of chemotherapy and had a
least six months of progression-free survival since the completion of chemotherapy.
Regardless of circumstances, no more than one prior chemotherapy regimen (including
chemo-radiotherapy) is permitted.
Patients who received prior chemotherapy must have recovered (Common Terminology
Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy
except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A
washout period of at least 21 days is required between last chemotherapy dose and
initiation of therapy.
Patients who received radiotherapy must have completed and fully recovered from the
acute effects of radiotherapy. A washout period of at least 14 days is required
between end of radiotherapy and initiation of therapy.
5. Patient must be able to swallow oral medications.
6. Patient must have an ECOG performance status of 0 to 1.
7. Patients must have adequate glucose control as defined by the following (both criteria
must be met):
• Fasting blood glucose (FBG) ≤140/dL (7.7mmol/L) AND
• Hemoglobin A1c (HbA1c) ≤6.4%
8. Patients must have adequate organ and marrow function as defined below NOTE:
Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower
limit of normal = LLN
Bone marrow function:
• Absolute neutrophil count (ANC) greater than or equal to 1500/mcl
• Platelets greater than or equal to 100,000 cells/mcl
• Hemoglobin greater than or equal to 8 g/dL (Patients may receive erythrocyte
transfusions to achieve this hemoglobin level at the discretion of the
investigator. Initial treatment must not begin earlier than the day after
erythrocyte transfusion).
Renal function:
• Creatinine Clearance ≥ 35 mL/min using Cockcroft-Gault formula
Pancreatic function:
• Fasting Serum amylase ≤ 2 × ULN
• Fasting Serum lipase ≤ ULN
Hepatic function:
• Bilirubin less than or equal to 1.5 x ULN (Patients with Gilbert's syndrome with
a total bilirubin ≤2 times ULN and direct bilirubin within normal limits are
permitted).
• ALT (alanine aminotransferase) and AST (aspartate aminotransferase) less than or
equal to 3 x ULN
• Alkaline phosphatase less than or equal to 2.5 x ULN
• Albumin greater than or equal to 2.8 g/dL
9. Patients must have signed an approved informed consent and authorization permitting
release of personal health information.
10. Patients must be at least 18 years of age.
11. Patients of childbearing potential must have a negative serum pregnancy test prior to
the study entry and be practicing a highly effective form of contraception during the
study treatment and for 8 weeks after stopping the treatment.
Highly effective contraception methods include combination of any of the following (oral,
injected, or implanted hormonal contraceptives are prohibited:
• Placement of an intrauterine device (IUD) or intrauterine system (IUS);
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault
caps) with spermicidal foam/gel/film/cream/vaginal suppository;
• Total abstinence or;
• Male/female sterilization. Women are considered post-menopausal and not of
child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea
with an appropriate clinical profile (e.g. age appropriate, history of vasomotor
symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy)
or tubal ligation at least six weeks prior to randomization. In the case of
oophorectomy alone, only when the reproductive status of the woman has been confirmed
by follow up hormone level assessment is she considered not of child-bearing
potential.
Exclusion Criteria:
1. Patients who have previously received any PIK3CA, PI3K, mTOR, or AKT inhibitor.
2. Patients with clear cell, serous, carcinosarcoma, mixed histology endometrial cancers,
or uterine sarcomas.
3. Known intolerance or hypersensitivity to alpelisib or fulvestrant, or any of their
excipients.
4. Patients who have previously received hormonal therapy for endometrial cancer.
5. Participant has had major surgery within 14 days prior to study treatment start and/or
has not recovered from major side effects.
6. Participant with an established diagnosis of diabetes mellitus type I or uncontrolled
type II (based on fasting blood glucose [FBG] and HemoglobinA1c [HbA1c], see INCLUSION
CRITERION 7)
7. Patients with concomitant invasive malignancy or a history of other invasive
malignancies, with the exception of non-melanoma skin cancer, are excluded if there is
any evidence of other malignancy being present within the past five years. Patients
are also excluded if their previous cancer treatment contraindicates this protocol.
8. Patients with active bacterial infection (requiring intravenous [IV] antibiotics at
time of initiating study treatment, fungal infection, or detectable viral infection
(such as known human immunodeficiency virus (HIV) positivity or with known active
hepatitis B or C [for example, hepatitis B surface antigen positive]). Screening is
not required for enrollment.
9. Patients with a serious pre-existing medical condition(s) that would preclude
participation in this study (for example: interstitial lung disease or pneumonitis,
severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (i.e.
estimated creatinine clearance <30ml/min), history of major surgical resection
involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative
colitis or pre-existing chronic condition resulting in baseline grade 2 or higher
diarrhea).
10. Patients with a known history of cardiac disease. This includes:
• Uncontrolled hypertension, defined as systolic greater than 150mm Hg or diastolic
greater than 90mm Hg despite antihypertensive medications
• Myocardial infarction, unstable angina, symptomatic pericarditis, or coronary
artery bypass graft (CABG) within 6 months prior to registration.
• New York Heart Association (NYHA) Class II or greater congestive heart failure.
• History of clinically significant cardiac arrhythmias (i.e. ventricular
tachycardia or ventricular fibrillation, complete left bundle branch block, high
grade AV block (e.g. bifascicular block, Mobitz type II and third degree AV block
without pacemaker in place) or serious cardiac arrhythmia requiring medication.
This does not include asymptomatic atrial fibrillation with controlled
ventricular rate.
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT
syndrome, or Fridericia QT correction formula (QTcF) > 470 msec at screening.
• Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6
months prior to the first date of study therapy.
• Syncope of cardiovascular etiology,
• Sudden cardiac arrest.
11. Participant is currently receiving any of the following medications and cannot be
discontinued 7 days prior to the start of the treatment:
• Strong CYP3A4 inducers
• Inhibitors of BCRP.
12. Patients who are pregnant or breast-feeding.
13. Patients with known central nervous system metastases which was not previously treated
and not fulfilling the following 3 criteria to be eligible for the study:
• Completed prior therapy (including radiation and/or surgery) for CNS metastases ≥
28 days prior to the start of study entry and
• CNS tumor is clinically stable at the time of screening and
• Participant is not receiving steroids and/or enzyme inducing anti-epileptic
medications for brain metastases.
14. Patients with an impairment of gastrointestinal function or gastrointestinal disease
that may significantly alter the absorption of the study drugs (i.e. ulcerative
disease; uncontrolled nausea, vomiting and/or diarrhea; malabsorption syndrome;
clinical signs and symptoms of gastrointestinal obstruction; and/or patients who
require parenteral hydration and/or nutrition).
15. Patients who plan to receive live attenuated vaccines within 1 week of start of
alpelisib and during the study. Patients should also avoid close contact with others
who have received live attenuated vaccines. Examples of live attenuated vaccines
include intranasal influenza, measles, mumps, rubella, oral polio, BCG< yellow fever,
varicella, and TY21a typhoid vaccines.
16. Patients with active bleeding or pathologic conditions that carry high risk of
bleeding such as known bleeding disorder or coagulopathy.
17. Patients who are currently part of or have participated in any clinical investigation
with an investigational drug within 30 days prior to dosing, or within 5 half-lives of
the investigational product, whichever is longer.
18. Patient is not able to understand and to comply with study instructions and
requirements, including oral administration of study treatment.
Endometroid Endometrial Cancer, Corpus Uteri, Uterus
Testing the Anti-Cancer Drug Darolutamide in Patients With Testosterone-driven Salivary Gland Cancers
This phase II trial tests how well darolutamide and leuprolide acetate work in treating
patients with androgen receptor positive salivary cancer that has spread from where it first
started (primary site) to other places in the body (metastatic), cannot be removed by surgery
(unresectable) or that has come back after a period of responding to prior therapy
(recurrent). Darolutamide is in a class of medications called androgen receptor inhibitors.
It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth
and spread of cancer cells. Leuprolide acetate is in a class of medications called
gonadotropin-releasing hormone (GnRH) agonists. It works by decreasing the amount of certain
hormones in the body. Giving darolutamide in combination with leuprolide acetate may help to
stop the growth of tumor cells that need androgens to grow or shrink them.
Justine Bruce, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05669664
Show full eligibility criteria
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Inclusion Criteria:
• Patients must have histologically or cytologically confirmed salivary gland cancer
that is recurrent/metastatic or unresectable/locally advanced, with AR expression
detected by immunohistochemistry (IHC) on a Clinical Laboratory Improvement Act
(CLIA)-approved assay. Androgen receptor testing by immunohistochemistry (IHC) can be
performed locally in a CLIA (Clinical Laboratory Improvement Amendments) certified lab
• Patients must have measurable disease
• Patients must have not had prior AR-targeted therapy, except for AR-targeted therapy
administered in the neoadjuvant and/or adjuvant setting and with disease recurrence
more than 6 months since treatment completion
• Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of darolutamide in combination with leuprolide acetate in patients < 18 years
of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Absolute neutrophil count >= 1,000/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (exception:
patients with elevated bilirubin due to Gilbert's disease would be eligible for the
trial)
• Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase ([SGPT])
=< 3 x institutional ULN
• Creatinine =< 1.5 x institutional ULN
• Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 (by Chronic Kidney Disease
Epidemiology Collaboration [CKD-EPI])
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
• The effects of darolutamide on the developing human fetus are unknown. For this reason
and because androgen receptor inhibitor agents as well as other therapeutic agents
used in this trial are known to be teratogenic (leuprolide-acetate), women of
child-bearing potential and men must agree to use adequate contraception (non-hormonal
or barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation. Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately. Men and women treated or enrolled on this protocol
must also agree to use adequate contraception prior to the study, for the duration of
study participation, and 7 days after completion of darolutamide administration or
after the depot interval for the leuprolide-acetate dose used has been completed,
whichever is longer
• Ability to understand and the willingness to sign a written informed consent document
• Patients must have tumors that are safely accessible for biopsy.
• Note: Two research biopsies are mandated in this trial. If the biopsy is deemed
to be unsafe after attempting the first biopsy, the patient will remain eligible
for the trial and subsequent tumor biopsies will not be required
Exclusion Criteria:
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1) with the exception of alopecia and
peripheral neuropathy
• Patients with a vascular or ischemic event within 6 months of study registration
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to darolutamide or leuprolide acetate
• Patients on combined P-gp and strong or moderate CYP3A inducers or BCRP substrates are
excluded. Because the lists of these agents are constantly changing, it is important
to regularly consult a frequently-updated medical reference. As part of the
enrollment/informed consent procedures, the patient will be counseled on the risk of
interactions with other agents, and what to do if new medications need to be
prescribed or if the patient is considering a new over-the-counter medicine or herbal
product
• Patients with uncontrolled intercurrent illness
• Pregnant women are excluded from this study because darolutamide is an androgen
receptor inhibitor agent with the potential for teratogenic or abortifacient effects.
Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with darolutamide and leuprolide-acetate,
breastfeeding should be discontinued if the mother is treated with darolutamide and
leuprolide-acetate. These potential risks may also apply to other agents used in this
study.
• Patients with moderate hepatic impairment (Child-Pugh Class B or C)
Locally Advanced Salivary Gland Carcinoma, Metastatic Salivary Gland Carcinoma, Recurrent Salivary Gland Carcinoma, Unresectable Salivary Gland Carcinoma, Lip, Oral Cavity and Pharynx, Head and Neck
A Study to Characterize the Safety, Tolerability, and Preliminary Efficacy of CFT1946 as Monotherapy and Combination Therapy in Subjects With BRAF V600 Mutant Solid Tumors
The purpose of this study is to evaluate the safety and tolerability of CFT1946 as well as to
determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of
CFT1946 as monotherapy (Arm A) and in combination with trametinib (CFT1946 + trametinib; Arm
B) or Cetuximab (CFT1946 + cetuximab; Arm C).
Vincent Ma, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05668585
Show full eligibility criteria
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Inclusion Criteria:
1. Subject (or legally authorized representative, where applicable) is willing and able
to provide signed informed consent and can follow protocol requirements
2. Subject is ≥18 years of age at time of informed consent
3. Eastern Cooperative Oncology Group performance status of 0 or 1
4. Subject has documented evidence of a BRAF V600 mutation obtained from tumor tissue or
liquid biopsy: (other protocol conditions may apply)
5. Subject must have received ≥1 prior line of SoC therapy for their unresectable locally
advanced or metastatic disease with disease progression on or after last prior
treatment. Prior regimens for these subjects vary by indication and investigational
arm, but must have included the following:
1. Melanoma or NSCLC (Phase 1 and Phase 2 Arms A1 and B1): Prior receipt of a BRAF
inhibitor and an immune checkpoint inhibitor (any sequence or combination). Prior
(neo)adjuvant immunotherapy may be acceptable.
2. CRC: Subjects must have received no more than 4 lines of prior therapy which
includes systemic chemotherapy-based regimen per SoC for unresectable locally
advanced or metastatic disease, and previous treatment with BRAF inhibitor in
combination with an EGFR monoclonal antibody. Subjects with documented MSI-H or
dMMR CRC must have received prior immunotherapy. Subjects with MSS disease must
have received at least 2 prior treatments. Subjects who received neo(adjuvant)
chemotherapy regimens may be eligible.
3. ATC: Subjects must have received SoC therapy options including BRAF inhibitor if
available and of benefit to the subject
4. Other BRAF V600 mutant solid tumors (non-CNS): Subjects must have received SoC
therapy options per their Investigator's best judgment, including BRAF inhibitor
if available and of benefit to the subject
6. Subject has measurable disease per RECIST v1.1
7. Adequate bone marrow, liver, renal, and cardiac function
8. A female subject may be eligible if not pregnant, planning a pregnancy, not breast
feeding, a women of non-child bearing potential or a WOCBP willing to comply with
protocol conditions relating to the use contraception, ova or blood donation and
pregnancy testing prior to the first dose
9. A male subject must agree to comply with protocol conditions relating to the use of
contraception, sperm and blood donation
10. Subject can safely swallow a tablet or pill
Other protocol defined exclusion criteria may apply
Exclusion Criteria:
1. Subject has had major surgery within 21 days prior to the planned first dose. Minor
surgery is permitted within 21 days prior to enrollment
2. Subject with CNS involvement (primary tumor or metastatic disease), except if
clinically stable, have no evidence of new or enlarging brain metastases and are on
stable or tapering doses of steroids for at least 7 days prior to first dose. Subjects
with untreated brain metastases may be eligible to enter without prior radiation
therapy.
3. Subject with known malignancy other than trial indication that is progressing or has
required treatment within the past 3 years, except for conditions that have undergone
potentially curative therapy
4. Subject with history of thromboembolic or cerebrovascular events ≤6 months as defined
in the protocol
5. Subject with impaired cardiac function or clinically significant cardiac disease, as
defined in the protocol
6. Subject with history of uncontrolled diabetes mellitus (only for subjects who will
receive CFT1946 + trametinib)
7. Subject with history or current evidence of retinal vein occlusion (RVO),
chorioretinopathy, or current risk factors for RVO (only for subjects who will receive
CFT1946 + trametinib)
8. Subject has received live, attenuated vaccine within 28 days prior to first dose
administration
9. Subject has history of pneumonitis or interstitial lung disease
10. Subject has history of uveitis
11. Subject has clinically significant gastrointestinal abnormalities.
12. Subject has known human immunodeficiency virus (HIV) infection (with exceptions)
13. Subject has history of or known HBV or active HCV infection
14. Subject has concurrent administration of strong CYP3A4/5 inhibitors and inducers,
including any herbal medications/supplements
15. Subject has presence of Grade ≥2 toxicity due to prior cancer therapy, excepting
alopecia and hypothyroidism requiring thyroid replacement therapy
16. Subject has initiation or receipt of the following ≤7 days prior to first dose
administration: Hematopoietic colony-stimulating growth factors, transfusion of packed
red blood cells (pRBC), and transfusion of platelets
17. Subject is pregnant, breastfeeding, or expecting to conceive or father children any
time during the study
Other protocol defined exclusion criteria may apply
Solid Tumors, Melanoma, NSCLC, CRC, ATC, Colon, Rectum, Lung, Melanoma, Skin, Thyroid, Colon and Rectum, Melanoma/Skin cancer
Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies
This phase I/II trial studies the best dose and side effects of peposertib and to see how
well it works with avelumab and hypofractionated radiation therapy in treating patients with
solid tumors and hepatobiliary malignancies that have spread to other places in the body
(advanced/metastatic). Peposertib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab,
may help the body's immune system attack the cancer, and may interfere with the ability of
tumor cells to grow and spread. Hypofractionated radiation therapy delivers higher doses of
radiation therapy over a shorter period of time and may kill more tumor cells and have fewer
side effects. Giving peposertib in combination with avelumab and hypofractionated radiation
therapy may work better than other standard chemotherapy, hormonal, targeted, or
immunotherapy medicines available in treating patients with solid tumors and hepatobiliary
malignancies.
Jeremy Kratz, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04068194
Show full eligibility criteria
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Inclusion Criteria:
• PHASE 1: Patients must have a histologically confirmed metastatic or locally advanced
unresectable solid tumor that has progressed on or after available standard of care
therapy or for which no acceptable standard of care therapy exists, or in which the
patient declines standard of care therapy (each patient that declines standard of care
therapy will be documented in the case report form)
• PHASE 2: Patients must have a histologically confirmed metastatic or locally advanced
unresectable cholangiocarcinoma/gallbladder carcinoma that has progressed on at least
1 prior standard of care therapy or for which no acceptable standard of care therapy
exists, or in which the patient declines standard of care therapy (each patient that
declines standard of care therapy will be documented in the case report form)
• Age >= 18 years
• Because no dosing or adverse event data are currently available on the use of
M3814 in combination with avelumab in patients < 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Patients with at least 1 index lesion to irradiate for whom palliative radiation
treatment is indicated (including but not limited to pain and/or symptom control,
prevention of disease -related complications, and preservation of organ function).
Lung and liver lesions are preferred, though alternate lesions may be considered after
discussion with trial principal investigator (PI). Up to 2 lesions may be considered
for irradiation provided at least 1 lesion will receive the study treatment of total
of 60 Gy and all prescribed irradiation will be completed within the radiation window
• Patients with at least 1 Response Evaluation Criteria in Solid Tumors (RECIST)
measurable lesion (to be unirradiated) (defined as those accurately measured in at
least one dimension, with the longest diameter to be recorded for non-nodal lesions
and the shortest diameter for nodal lesions). Measurable is defined as at least 10 mm
in longest diameter for solid tumors, at least 15 mm in shortest diameter for lymph
nodes
• Patients must be willing to undergo fresh biopsies at baseline (as opposed to using
archival tissue), in the event their baseline tissue was obtained > 12 months prior to
study consent and/or they are randomized to the gamma H2AX pNBS1 multiplex IFA assay
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelet count >= 100,000/mcL
• Hemoglobin >= 9.0 g/dL
• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR calculated serum creatinine
clearance (glomerular filtration rate [GFR] can be used in place of creatinine or
creatinine clearance) >= 60 mL/min for participants with creatinine levels > 1.5 x
institutional ULN
• Calculate serum creatinine clearance using the standard Cockcroft-Gault formula
• Serum total bilirubin =< 1.5 x ULN or direct bilirubin =< ULN for participants with
total bilirubin > 1.5 x ULN
• Patients with known Gilbert disease with serum bilirubin level =< 3 x ULN are
eligible
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
ULN or =< 5.0 x ULN for patients with hepatobiliary tumors/liver metastases
• Albumin >= 2.8 g/L
• International normalized ratio (INR) or prothrombin time (PT) or activated partial
thromboplastin time (aPTT) =< 1.5 x ULN
• This applies only to patients not receiving therapeutic anticoagulation; patients
receiving therapeutic anticoagulation should be on a stable dose
• Participants must have the ability to swallow and retain oral medication and not have
any clinically significant gastrointestinal abnormalities that might alter absorption
• Female patients of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required. The effects of M3814 and avelumab on the developing human fetus
are unknown and there is the potential for teratogenic or abortifacient effects. For
this reason, women and men of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry, for the duration of study treatment, and for 6 months after completion of M3814
and avelumab administration. Should a woman become pregnant or suspect she is pregnant
while she or her partner is participating in this study, she should inform her
treating physician immediately. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with M3814 and
avelumab, breastfeeding should be discontinued if the mother is treated with M3814 and
avelumab
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a close caregiver
or legally authorized representative (LAR) and/or family member available will also be
eligible
Exclusion Criteria:
• PHASE I: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other
immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents
• PHASE II: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other
immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents with
the following exceptions:
• Patients who have only received previous durvalumab (anti-PD-L1) in combination
with gemcitabine +/- cisplatin as part of first line therapy (TOPAZ-1 regimen)
are eligible
• Patients who have only received previous pembrolizumab (anti-PD-1) in combination
with gemcitabine +/- cisplatin as part of first line therapy (KEYNOTE-966
regimen) are eligible
• Patients who have had chemotherapy, definitive radiation, biological cancer therapy,
or investigational agent/device within 21 days of first planned dose of study therapy
(within 14 days for palliative radiation). Previously irradiated lesions may be
re-irradiated provided there is disease progression in the irradiated lesion and the
prescribed radiation dosage can safely be re- administered
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > Common Terminology Criteria for Adverse Events
[CTCAE] grade 1) with the exception of alopecia
• Patients with untreated/uncontrolled central nervous system (CNS)/leptomeningeal
disease. Patients with asymptomatic, treated CNS disease are eligible if the treating
physician determines that immediate CNS specific treatment is not required and is
unlikely to be required during the first cycle of therapy and the following criteria
are met:
• Radiographic demonstration of clinical stability upon the completion of
CNS-directed therapy and no evidence of interim progression between the
completion of CNS-directed therapy and the screening radiographic study done >= 4
weeks from completion of radiotherapy and >= 2 weeks from discontinuation of
corticosteroids
• No stereotactic radiation or whole-brain radiation within 28 days prior to
randomization
• Patients with active autoimmune disease requiring systemic corticosteroids greater
than the equivalent of prednisone 10 mg daily including but not limited to: systemic
lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, colitis,
vascular thrombosis associated with antiphospholipid syndrome, Wegener's
granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple
sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis, with the
following exceptions:
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone are eligible
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are
eligible
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
dermatologic manifestations only who require only low potency topical steroids
(e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%,
desonide 0.05%, alclometasone dipropionate 0.05%) are eligible
• Patients receiving treatment with systemic immunosuppressive medications (including,
but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate,
thalidomide, and anti-tumor necrosis factor [TNF] agents) within 6 weeks must
discontinue these medications prior to starting M3814 and avelumab on day 7, with the
exception of:
• Patients with active autoimmune disease managed with systemic corticosteroids
less than the equivalent of prednisone 10 mg daily
• Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea)
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
for patients with orthostatic hypotension and adrenocortical insufficiency
• Patients who have undergone prior solid organ or bone marrow transplant with the
exception of patients with prior renal transplant for whom dialysis may be employed in
the event of graft rejection
• Patients with uncontrolled intercurrent illness (e.g., including but not limited to
uncontrolled hypertension [HTN] [systolic blood pressure (BP) > 150, diastolic BP >
100], symptomatic congestive heart failure [CHF], unstable angina pectoris, ischemic
myocardial infarction [MI] within 6 months, cardiac arrhythmia, recent transient
ischemic attack [TIA or cerebrovascular accident (CVA)]) within 6 months
• Patients with serious active infection (e.g. requiring hospitalization and/or
intravenous [IV] antibiotics) within 4 weeks prior to starting M3814 and avelumab, or
signs/symptoms of infection or receiving oral or IV antibiotics for the treatment of
active systemic infection within 2 weeks prior to starting M3814 and avelumab.
Patients receiving prophylactic antibiotics are eligible
• Patients with known chronic hepatitis B virus (HBV) infection must have an
undetectable viral load on suppressive therapy if indicated. Patients with known
chronic hepatitis C (HCV) infection must have been treated and cured. Patients who are
currently on curative treatment are eligible if they have an undetectable HCV viral
load
• Patients with known human immunodeficiency virus (HIV) are allowed on study provided
they have:
• A stable regimen of highly active anti-retroviral therapy (HAART)
• No requirement for concurrent antibiotics or antifungal agents for the prevention
of opportunistic infection
• A CD4 count above 250 cells/mcL
• An undetectable HIV viral load on standard polymerase chain reaction (PCR)-based
testing
• Patients with history of idiopathic pulmonary fibrosis, pneumonitis (including drug
induced), organizing pneumonia (e.g., bronchiolitis obliterans, cryptogenic organizing
pneumonia), or evidence of active pneumonitis on screening chest computed tomography
(CT) scan
• Patients with known concurrent malignancy that is expected to require active treatment
within two years, or may interfere with the interpretation of the efficacy and safety
outcomes of this study in the opinion of the treating investigator. Superficial
bladder cancer, nonmelanoma skin cancers, and low-grade prostate cancer not requiring
cytotoxic therapy should not exclude participation in this trial. Patients with
chronic lymphocytic leukemia (CLL) may be enrolled if they do not require active
chemotherapy and their hematologic, renal and hepatic function meets criteria
previously mentioned
• Patients with psychiatric illness/social situations that would limit compliance with
study requirements
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to M3814 or avelumab
• Patients unable to discontinue medications or substances that are potent inhibitors,
inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to starting M3814 and
avelumab are ineligible. Medications or substances that are strong inhibitors of
CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first M3814 dose.
Strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the
first dose. Drugs mainly metabolized by CYP3A with a narrow therapeutic index as
judged by the investigator must stop at least 1 day prior to first M3814 dose. Because
the lists of these agents are constantly changing, it is important to regularly
consult a frequently-updated medical reference. As part of the enrollment/informed
consent procedures, the patient will be counseled on the risk of interactions with
other agents, and what to do if new medications need to be prescribed or if the
patient is considering a new over-the-counter medicine or herbal product. The primary
elimination mechanism of avelumab is proteolytic degradation, thus there are no
contraindicated medications with respect to avelumab
• Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs) prior to
starting M3814 and avelumab. These must be discontinued >= 5 days prior to starting
M3814 and avelumab. Patients do not need to discontinue calcium carbonate. H2 blockers
are allowed provided they are taken at least 2 hours after M3814 dose
• Patients receiving sorivudine or any chemically related analogues (such as brivudine)
and not able to discontinue prior to starting M3814 and avelumab are excluded
• Pregnant and lactating women are excluded from this study because M3814 and avelumab
are agents with the potential for teratogenic or abortifacient effects. Because there
is an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with M3814 and avelumab, breastfeeding should be discontinued
if the mother is treated with M3814 and avelumab
• Patients who have received live vaccination within 30 days before starting M3814 and
avelumab
Cholangiocarcinoma, Gallbladder Carcinoma, Stage III Gallbladder Cancer AJCC v8, Stage III Hilar Cholangiocarcinoma AJCC v8, Stage III Intrahepatic Cholangiocarcinoma AJCC v8, Stage IV Gallbladder Cancer AJCC v8, Stage IV Hilar Cholangiocarcinoma AJCC v8, Stage IV Intrahepatic Cholangiocarcinoma AJCC v8, Liver, Other Digestive Organ, Gastrointestinal cancers, other
Outcomes and Cosmesis With Whole Breast Irradiation and Boost
This study is being done to evaluate cosmetic, patient-reported outcome measures (PROMs), and
toxicities for women undergoing ultra-short whole breast irradiation (WBI) therapy with
simultaneous integrated boost (SIB). 50 participants will be on study for up to 60 months.
Jessica Schuster, MD
Female
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT06295744
Show full eligibility criteria
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Inclusion Criteria:
• Ability to understand and the willingness to sign a written informed consent document
• Histologically confirmed early stage (stage T1-T2) invasive carcinoma of the breast or
DCIS
• Breast conserving surgery with negative margins and negative nodes (surgical axillary
staging not mandatory), stage N0 or Nx
• Treatment plan should include breast conserving surgery and adjuvant whole breast
irradiation (WBI) therapy delivered with 3D-CRT or IMRT techniques
• Treatment plan includes breast tumor bed boost
• Willingness to comply with all study procedures and be available for the duration of
the study
Exclusion Criteria:
• Mastectomy of ipsilateral breast
• Lack of histologic diagnosis
• Histologic involvement of the axillary or regional nodes or metastatic disease
• Accelerated partial breast irradiation treatment plan
• Previous history of non-breast malignancy diagnosed in the past 5 years except for
basal or squamous cell cancer of the skin
• Previous history of chest radiation therapy
• Previous history of ipsilateral breast cancer
• Concurrent cytotoxic chemotherapy
• Active connective tissue disease including scleroderma
• Inability or unwillingness to return for required follow up visit
Study of BMS-986393 a GPRC5D-directed CAR T Cell Therapy in Adult Participants With Relapsed or Refractory Multiple Myeloma (QUINTESSENTIAL)
The purpose of this study is to evaluate the effectiveness and safety of BMS-986393 in
participants with relapsed or refractory multiple myeloma.
Zhubin Gahvari, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT06297226
Show full eligibility criteria
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Inclusion Criteria
• Documented diagnosis of multiple Mmyeloma (MM) as per International Myeloma Working
Group (IMWG) criteria.
• Received at least 4 classes of MM treatment [including immunomodulatory drug (IMiD),
proteasome inhibitor (PI), anti CD38 mAb, and anti-B cell maturation antigen (BCMA)
therapy], and at least 3 prior lines of therapy (LOT).
• Documented disease progression during or after their last anti-myeloma regimen as per
IMWG.
• Participants must have measurable disease during screening.
• Have measurable disease during screening.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion Criteria
• Active or history of central nervous system involvement with MM.
• Active systemic fungal, bacterial, viral, or other infection despite appropriate
anti-infective treatment at the time of leukapheresis.
• Received any prior therapy directed at G protein-coupled receptor class C, group 5,
member D (GPRC5D) or has received other prior treatment for MM without the required
washout prior to leukapheresis.
• Other protocol-defined Inclusion/Exclusion criteria apply.
Pembrolizumab, INCB081776, and Radiation Therapy for Head and Neck Squamous Cell Carcinoma
This study is evaluating INCB081776 when given in combination with the checkpoint inhibitor
pembrolizumab and palliative radiation therapy in patients with metastatic or recurrent
metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). 12 participants will
be enrolled and can expect to be on study for up to 12 months.
Justine Bruce, MD
All
18 Years and over
Early Phase 1
This study is NOT accepting healthy volunteers
NCT06308913
Show full eligibility criteria
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Inclusion Criteria:
• Participants must have histologic or cytologic evidence of head and neck squamous cell
carcinoma (HNSCC) that is metastatic or recurrent and therefore considered incurable.
Cutaneous skin squamous cell carcinomas located in the head and neck region are
eligible after discussion with the Sponsor-Investigator.
• Measurable disease that are considered non-amenable to surgery or other curative
treatments or procedures, with at least 1 target lesion available for evaluation.
• The preference is for measurable disease to be selected from a site that has not
received any prior radiation or locoregional therapy. However, if a tumor lesion
is situated in a previously irradiated area, or in an area subjected to other
prior locoregional therapy, the lesion should demonstrate disease progression
after the prior treatment.
• Prior cancer treatment must be completed at least 14 days prior to enrollment (for
chemotherapy, targeted small molecular therapy, or radiation therapy. Prior treatment
with a monoclonal antibody must be completed at least 28 days prior to enrollment.
Participants must have recovered from all reversible acute toxic effects of the
regimen (other than alopecia) to ≤ Grade 1 or baseline.
• Participants must have two "index" tumors that meet the following criteria:
• Index tumor A (lesion to receive palliative radiation therapy):
• is deemed by the treating radiation oncologist to potentially benefit from
palliative radiation
• is at least 1 cm in longest dimension
• Index tumor B (lesion to undergo biopsy):
• Is deemed by the treating physician to be amenable to biopsy
• Is at least 1 cm in longest dimension.
• Participants must be willing to provide at least 2 research biopsies (up to
3 research biopsies) during the conduct of the study.
• Note: If a subject is scheduled to have a baseline or on-study tumor biopsy,
and the investigator believes that the tumor tissue cannot be obtained
safely, then the biopsy may be omitted with approval by the
Sponsor-Investigator. The participant may be replaced in order to enroll
sufficient number of subjects for biomarker evaluation.
• Note: Care should be taken to biopsy the same lesions for research samples.
The preference is for the same lesion to be biopsied at all time points. If
a lesion is no longer amenable for a research biopsy (for examples: due to a
decrease in size, becomes inaccessible, is not safe/feasible for a biopsy),
then an alternative lesion may be utilized with approval by the
Sponsor-Investigator. Index tumor B (lesion to undergo biopsy) must not have
received palliative radiation therapy during the study.
• Participants must be willing to provide at least 2 collections of fresh research
biopsies (up to 3 fresh research biopsies) during the conduct of this study.
• Research biopsy #1 (baseline, mandatory). Archival tissue obtained since
completion of last therapy may be used.
• Research biopsy #2 (cycle 1 days 9-14, after treatment with INCB081776 but prior
to pembrolizumab, mandatory)
• Research biopsy #3 (cycle 1 day 37-56, after treatment with INCB081776,
pembrolizumab and palliative RT). For participants who had baseline archival
tissue collected (no baseline research biopsy was obtained), this fresh core
biopsy is mandatory. For participants who underwent a fresh core research biopsy
at baseline, this biopsy is optional.
• Note: If a participant is scheduled to have an on-study tumor biopsy, and the
investigator believes that the tumor tissue cannot be obtained safely, then the
biopsy may be omitted after discussion with the Sponsor-Investigator. The
participant may be replaced in order to enroll sufficient number of subjects for
biomarker evaluation.
• Note: Care should be taken to biopsy the same lesion for the on-treatment samples
Exclusion Criteria:
• Subjects with significant intercurrent illnesses per physician discretion.
• Subjects with a diagnosed auto-immune disease requiring systemic treatment with
immunosuppressants.
• Subjects with known genetic conditions causing pre-disposition to RT toxicity (i.e:
Li-Fraumeni, ATM deficiency, active scleroderma, etc.).
• Subjects with known retinal or ophthalmologic disorders or conditions. Subjects with
macular degeneration, proliferative diabetic retinopathy or diabetic retinopathy with
macular edema, retinal vein occlusions, uveitis, central serous retinopathy, leukemic
retinopathy, inherited retinal degenerations, known family history of inherited
retinal degenerations, and subjects at risk for angle closure glaucoma from pupillary
dilation are ineligible. Subjects with other clinically significant abnormalities
identified during ophthalmic screening examinations that may confound ocular
monitoring are ineligible.
Lip, Oral Cavity and Pharynx, Esophagus, Larynx, Head and Neck, Head and Neck Squamous Cell Carcinoma
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations (SEACRAFT-1)
To evaluate the efficacy of naporafenib administered with trametinib in patients with rat
sarcoma viral oncogene (RAS) Q61X solid tumors
- To evaluate the safety and tolerability of naporafenib administered with trametinib in
patients with RAS Q61X solid tumors
- To characterize the pharmacokinetic (PK) profile of naporafenib and trametinib when
administered to patients with RAS Q61X solid tumors
Dustin Deming, MD
All
12 Years to 99 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT05907304
Show full eligibility criteria
Hide eligibility criteria
Key
Inclusion Criteria:
1. Willing and able to provide written informed consent
2. Age ≥ 12 years
3. A locally advanced or metastatic tumor who has progressed on or for which no standard
therapy exists. Patients who are intolerant to standard therapy or who are not a
candidate for standard therapy (in the opinion of the Investigator) or who decline
standard therapy are also eligible.
4. Documentation of a RAS Q61X mutation (tumor tissue or blood) prior to first dose of
study treatment as determined locally with an analytically validated assay in a
certified testing laboratory.
5. Archival tumor tissue collected within 5 years prior to enrollment must be confirmed
to be available at the time of Screening, which may be submitted before or after
enrollment for exploratory biomarker analysis.
6. ECOG performance status 0, 1 or 2
7. Presence of at least 1 measurable lesion according to RECIST v1.1
8. Able to swallow oral medication.
Exclusion Criteria:
1. Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
2. Impairment of GI function or gastrointestinal (GI) disease that may significantly
alter the absorption of study treatment (e.g., ulcerative diseases, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
3. History or current evidence of retinal vein occlusion (RVO) or current risk factors
for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity
or hypercoagulability syndrome)
4. Corrected QT interval using Fridericia's formula (QTcF) at Screening >450 ms based on
triplicate average NOTE: criterion does not apply to patients with a right or left
bundle branch block
5. LVEF <50%
6. All primary CNS tumors
7. Symptomatic CNS metastases that are neurologically unstable. Patients with controlled
CNS metastases are eligible.
8. Patients receiving treatment with medications that are known to be strong inhibitors
and/or inducers of cytochrome P450 (CYP)3A; substrates of CYP2C8, CYP2C9, and CYP3A
with a narrow therapeutic index and sensitive substrates of CYP3A;
9. Are pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the trial
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus, Advanced or Metastatic Solid Tumors
*Note: Email is generally not a secure way to communicate sensitive or health-related information as there are many ways for unauthorized users to access email. You should avoid sending sensitive, detailed personal information by email.