Search Results
within category "Digestive Health & Liver Disease"
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.
(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination
with sunitinib. This is a multi-part study that will enroll approximately 426 patients. Part
1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to
be used in subsequent parts in approximately 20 patients who have received at least one prior
line of therapy for GIST and 2) evaluating for drug-drug interactions between CGT9486 and
sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase
inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388
patients who are intolerant to, or who failed prior treatment with imatinib only and will
compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being
randomized in a 1:1 manner.
Howard Bailey, M.D.
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05208047
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Key
Inclusion Criteria:
1. Histologically confirmed locally advanced, metastatic, and/or unresectable GIST.
Molecular pathology report must be available for Part 2; if molecular pathology report
is unavailable or inadequate, an archival or fresh tumor tissue sample will be
required to evaluate mutational status prior to randomization.
2. Documented disease progression on or intolerance to imatinib
3. Subjects must have received the following treatment:
• Part 1a: Treatment with ≥1 prior lines of therapy for GIST
• Part 1b: Treatment with ≥2 prior TKI for GISTs
• Part 2: Prior treatment with imatinib only
4. Have at least 1 measurable lesion according to mRECIST v1.1
5. ECOG •0 to 2
6. Have clinically acceptable local laboratory screening results (clinical chemistry and
hematology) within certain limits
Key
Exclusion Criteria:
1. Known PDGFR driving mutations or known succinate dehydrogenase deficiency
2. Clinically significant cardiac disease
3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study
drug
4. Gastrointestinal abnormalities including, but not limited to, significant nausea and
vomiting, malabsorption, external biliary shunt, or significant bowel resection that
would preclude adequate absorption
5. Any active bleeding excluding hemorrhoidal or gum bleeding
6. Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis
C virus (HCV) antibody.
7. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
8. Received strong CYP3A4 inhibitors or inducers
9. Received sunitinib within 3 weeks (Part 1a, Part 1b)
Pilot Study of Imatinib Cetuximab Combo for H & N Cancer
The goal of this clinical trial is to find if levels of a protein called AXL in tumor cells
relate to how tumors respond to cetuximab (CTX) combined with imatinib in participants with
head and neck cancer. This interventional study will occur in the time between diagnosis of
your cancer and surgery to remove your tumor or radiation or chemoradiation treatment of your
primary cancer.
Participants will undergo a research blood draw and a research biopsy as part of the
screening process, and will be in this research study for approximately 13 to 16 months.
Justine Bruce, MD
All
18 Years and over
Early Phase 1
This study is NOT accepting healthy volunteers
NCT05816785
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Inclusion Criteria:
• Age > 18 years at the time of consent.
• Histological confirmation of squamous cell carcinoma of the head and neck.
• For those patients with oropharyngeal cancer, subjects must have either
• HPV-negative status by p16 expression or HPV-DNA Expression.
• HPV-positive status by p16 expression AND a >10 pack year smoking history.
• Subjects must be appropriate candidates for definitive curative intent treatment,
either via surgical resection, definitive radiation therapy alone, or definitive
concurrent chemoradiation therapy.
• For the screening research biopsy, subjects must have sufficient tumor volume
(approximately 10 cc) to accommodate at minimum 2-3 core samples for the research
biopsy.
• For the post-treatment (CTX/Imatinib) research biopsy, subjects who are scheduled to
receive definitive radiation therapy (+/- concurrent chemotherapy) are required to
have sufficient tumor volume to accommodate at minimum 2-3 core samples for the
research biopsy.
• Demonstrate adequate organ function; all screening labs to be obtained within 28 days
prior to registration.
Exclusion Criteria:
• Subjects with a diagnosis of nasopharyngeal carcinoma, advanced cutaneous squamous
cell carcinoma of the head and neck, or salivary gland tumors are excluded from this
study.
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.
active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable
safety risks or compromise compliance with the protocol.
• Prior chemotherapy, radiotherapy, or major surgery within 8 weeks of study enrollment
or those who have not recovered (to grade ≤ 1 or baseline) from clinically significant
adverse events due to agents administered more than 8 weeks earlier (alopecia and
fatigue excluded). Clinical significance to be determined by the study investigator.
• Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study.
• Subjects who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to imatinib or CTX.
Head and Neck Cancer, Squamous Cell Carcinoma of Head and Neck, Lip, Oral Cavity and Pharynx, Esophagus, Head and Neck
Study of DF9001 in Patients With Advanced Solid Tumors
DF9001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell
activation signals to specific receptors on cancer cells. The study will occur in two phases.
The first phase will be a dose escalation phase, enrolling patients with various types of
solid tumors that express epidermal growth factor receptor (EGFR). A combination therapy
cohort will be opened for enrollment, DF9001 + nivolumab. The second phase will include a
dose expansion using the best dose selected from the first phase of the study. Multiple
cohorts will be opened with eligible patients having selected solid tumors.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05597839
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Inclusion Criteria:
General (applies to all cohorts)
1. Signed written informed consent.
2. Male or female patients aged ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
and an estimated life expectancy of at least 3 months.
4. Adequate hematological function.
5. Adequate hepatic function.
6. Adequate renal function.
7. Effective contraception for women of child bearing potential (WOCBP) patients as
defined by World Health Organization (WHO) guidelines for 1 "highly effective" method
or 2 "effective" methods.
Inclusion Criteria:
Dose Escalation (Monotherapy and Combination)
1. Histologically or cytologically proven locally advanced or metastatic solid tumors of
epithelial origin with documented EGFR expression on tumor tissue by IHC and must have
progressed on standard of care therapy.
2. Evidence of objective disease, but participation does not require a measurable lesion.
Inclusion Criteria:
Safety PK/PD Expansion Cohorts
1. Histologically or cytologically proven locally advanced or metastatic solid tumor from
the following list, where standard therapy has failed, that has been confirmed to have
EGFR expression via archival or fresh biopsy tissue prior to study enrollment.
i. NSCLC ii. HNSCC iii. CRC iv. Esophageal adenocarcinoma v. Gastric cancer vi. Renal
cell carcinoma vii. Pancreatic cancer
2. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
3. Able and willing to have a fresh tumor biopsy obtained during the screening window and
an on-treatment biopsy for pharmacodynamic analysis.
Inclusion Criteria:
Head and Neck Squamous Cell Carcinoma (HNSCC) Expansion Cohorts
1. Histologically or cytologically documented relapsed or metastatic HNSCC that has been
confirmed to have EGFR expression via archival or fresh biopsy tissue prior to study
enrollment. Primary tumor locations include oropharynx, oral cavity, hypopharynx, or
larynx. Participants may not have a primary tumor site of nasopharynx (any histology).
2. Participants must have radiographic disease progression while on or after having
received both platinum-based chemotherapy and an anti-PD-(L)1 antibody, administered
either concurrent or sequentially.
3. Documented EGFR expression by IHC.
4. Able and willing to have a fresh tumor biopsy obtained during the screening window and
an on-treatment biopsy for pharmacodynamic analysis.
Inclusion Criteria:
Colorectal Cancer (CRC) Expansion Cohorts
1. Histologically or cytologically documented relapsed or metastatic colorectal cancer
that has been confirmed to have EGFR expression via archival or fresh biopsy tissue
prior to study enrollment.
2. Must have received 1 line of either FOLFOX, CAPOX, FOLFIRI, or FOLFOXIRI with or
without a biological agent. Prior treatment with an anti-EGFR antibody is required for
RAS wild-type participants.
3. Participants cannot be known mismatch repair (MMR)/MSI high.
4. Participants must not have received an anti-PD-(L)1.
5. Participants must have radiographic disease progression while or after receiving
treatment for their advanced (recurrent/unresectable/metastatic) disease.
6. Presence of at least 1 tumor lesion accessible for biopsy. A fresh tumor biopsy must
be obtained and shipped for analysis at the Sponsor-designated laboratory during the
screening window and while on study treatment in accordance with the study Laboratory
Manual.
Inclusion Criteria:
Non-Small Cell Lung Cancer (NSCLC) Expansion Cohorts
1. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV (per
the 7th IASCLC classification of NSCLC), or recurrent disease that has been confirmed
to have EGFR expression via archival or fresh biopsy tissue prior to study enrollment.
2. Patients must have recurrent or progressive disease during or after first line
combination therapy with checkpoint inhibitors and platinum-based chemotherapy. They
must not have received any subsequent lines of therapy.
3. Patients with Stage IIIB must be ineligible for local therapies with curative intent
(eg, radiotherapy or surgery).
4. Patients must have received and progressed on or after anti-PD-(L)1 therapy including
those with actionable genomic alterations.
5. Status for actionable mutations (EGFR, ALK, ROS1, RET, etc.) must be known (when
testing is available as per country/region standard of care practices); patients with
actionable mutations must have received and progressed on, have been intolerant to, or
not be a candidate for standard TKIs (as available per country/region standard of care
practices).
6. Presence of at least 1 tumor lesion accessible for biopsy. A fresh tumor biopsy must
be obtained and shipped for analysis at the Sponsor-designated laboratory during the
screening window and while on study treatment in accordance with the study Laboratory
Manual.
Exclusion Criteria:
1. Participants must not have had chemotherapy, radiotherapy (other than palliative
bone-directed radiotherapy), or major surgery, or received another investigational
agent within 28 days or 5-half-lives of the drug (if known), whichever is shorter,
before the start of study treatment.
2. Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [except for
palliative bone-directed radiotherapy], immune therapy, or cytokine therapy [except
for erythropoietin]), major surgery (excluding prior diagnostic biopsy), concurrent
systemic therapy with steroids or other immunosuppressive agents, or use of any
investigational drug within 28 days or 5-half-lives of the drug (if known), whichever
is shorter, before the start of study treatment. Short-term administration of systemic
steroids (eg, for allergic reactions or the management of irAEs) is allowed.
Note: Participants receiving bisphosphonate or denosumab are eligible, provided
treatment was initiated at least 14 days before the first dose of DF9001.
3. Previous malignant disease other than the target malignancy to be investigated in this
study within the last 3 years, with the exception of basal or squamous cell carcinoma
of the skin, low-grade prostate cancer (Gleason score of ≤6), or cervical carcinoma in
situ.
4. Life expectancy of less than 3 months.
5. Participants with brain metastases are excluded, unless all of the following criteria
are met:
• Central nervous system (CNS) lesions are asymptomatic, previously treated and no
active therapy is required (i.e., no steroids for edema).
• Imaging demonstrates stability of disease 28 days from last treatment for CNS
metastases.
6. Receipt of any organ transplantation, including autologous or allogeneic stem-cell
transplantation.
7. Significant acute or chronic infections (including historic positive test for human
immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C
tested during the screening window). If HBsAg is negative and the anti-hepatitis B
core antibody is positive, then hepatitis B viral DNA load must be undetectable.
8. Preexisting autoimmune disease (except for participants with vitiligo) needing
treatment with systemic immunosuppressive agents for more than 28 days within the last
3 years, or clinically relevant immunodeficiencies (eg, dysgammaglobulinemia or
congenital immunodeficiencies). Participants with a history of immune related
endocrinopathies (e.g. hypothyroidism, type 1 diabetes mellitus [TIDM] and adrenal
insufficiency) that are stable on hormone replacement therapy may be eligible for this
study.
9. Participants with a known medical history that may place them at risk of known
toxicities of EGFR-blockage.
• History of or ongoing keratitis, ulcerative keratitis, or corneal perforation,
• History of cardiopulmonary arrest unless this was caused by an acute, reversible
etiology that is no longer present.
• History of or ongoing pulmonary fibrosis or interstitial lung disease.
10. Known severe hypersensitivity reactions to monoclonal antibodies (≥Grade 3 of the
NCI-CTCAE v5.0), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more
features of partly controlled asthma).
11. Persisting toxicity related to prior therapy >Grade 1 NCI-CTCAE v5.0; however,
alopecia ≤Grade 2, endocrinopathies ≤Grade 2, and sensory neuropathy ≤Grade 2 is
acceptable.
12. Participants who have received an anti-PD-(L)1 as a previous line of therapy are
eligible for the study, unless they have experienced either:
• a Grade 3 or 4 drug-related toxicity during and attributed to treatment with the
anti-PD-(L)1.
• a Grade 2 drug-related toxicity that impacted either the lungs or the nervous
system, caused by the administration of the anti-PD-(L)1.
13. Pregnancy or lactation in females during the study.
14. Known alcohol or drug abuse.
15. Serious cardiac illness or medical conditions, including but not limited to:
• History of New York Heart Association class III or IV heart failure or systolic
dysfunction (left ventricular ejection fraction [LVEF] <55%).
• High-risk uncontrolled arrhythmias (eg, tachycardia with a heart rate >100/min at
rest).
• Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade
atrioventricular (AV) block (eg, AV-block, second degree AV block Type 2 [Mobitz
2], or third-degree AV-block).
• Angina pectoris requiring anti-anginal medication.
• Clinically significant valvular heart disease.
• Evidence of transmural infarction on ECGs.
• Poorly controlled hypertension (defined as systolic >160 mm Hg or diastolic >100
mm Hg).
• Clinically relevant uncontrolled cardiac risk factors, clinically relevant
pulmonary disease, or any clinically relevant medical condition in the opinion of
the Investigator that may limit participation in this study.
• Severe dyspnea at rest due to complications of advanced malignancy or requiring
supplementary oxygen therapy.
16. All other significant diseases (eg, inflammatory bowel disease), which, in the opinion
of the Investigator, might impair the participant's ability to participate.
17. Any psychiatric condition that would prohibit the understanding or rendering of
informed consent.
18. Legal incapacity or limited legal capacity.
19. Incapable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the ICF and in this protocol.
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, Solid Tumor, Adult
Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma
This phase II trial studies the effect of duvelisib or CC-486 and usual chemotherapy
consisting of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone in
treating patients with peripheral T-cell lymphoma. Duvelisib may stop the growth of cancer
cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as
CC-486, cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. This trial may help find out if this
approach is better or worse than the usual approach for treating peripheral T-cell lymphoma.
Saurabh Rajguru, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04803201
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Inclusion Criteria:
• Histologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) with < 10%
CD30 expression by immunohistochemistry in the following subtypes (by local review):
nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (TFH-PTCL), follicular
T-cell lymphoma, PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell
lymphoma (AITL), enteropathy associated T-cell lymphoma, monomorphic epitheliotropic
intestinal T-cell lymphoma
• Patients with expression of CD30 in >= 10% of the tumor (based on local
immunohistochemistry review) regardless of histology will not be permitted
• Patients with a diagnosis of other PTCL subtype histologies other than those
specified in the inclusion criteria are excluded including large cell
transformation of mycosis fungoides
• Patients will be stratified by presence or absence of TFH phenotype (i.e.
diagnosis of AITL, TFH-PTCL, follicular T-cell lymphoma) based on local review of
pathology. Determination of TFH phenotype can be defined by expression of two or
more of the following markers CD10, BCL6, CXCL13, ICOS, and PD1 by
immunohistochemistry
• Measurable disease as defined by the Lugano criteria
• No prior systemic therapy for lymphoma (excluding corticosteroids)
• Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
are unknown. Therefore, for women of childbearing potential only, a negative urine or
serum pregnancy test done =< 7 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Platelet count >= 75,000/mm^3 (>= 50,000/mm^3 if secondary to bone marrow involvement
from lymphoma per investigator assessment; the first 12 patients on each arm of the
study must have platelets >= 75,000/mm^3 regardless of bone marrow involvement)
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or
alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3.0 x
upper limit of normal (ULN)
* Except in subjects with documented liver involvement by lymphoma
• Calculated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula
• Total bilirubin =< 2.0 x ULN
* Except in cases of Gilbert's Syndrome or documented liver or pancreatic involvement
by lymphoma
• Archival tissue must be available for submission
• Patients known to have HTLV 1/2 are excluded
• Patients with known central nervous system involvement are excluded
• No active viral infection with human immunodeficiency virus (HIV), hepatitis B, or
hepatitis C. Those who are seropositive (e.g. hepatitis B core antibody [Ab] positive)
are permitted if they are negative by polymerase chain reaction (PCR). Those who are
seropositive for hepatitis B and are negative for hepatitis B virus (HBV)
deoxyribonucleic acid (DNA) by PCR must receive concomitant hepatitis B directed
antiviral therapy. Those who have hepatitis C Ab positivity who have completed
curative therapy for hepatitis C with negative hepatitis C PCR are eligible
• Patients with history of HIV are eligible if they have an undetectable viral load for
at least 6 months
• No active uncontrolled systemic fungal, bacterial or viral infection (defined as
ongoing signs/symptoms related to the infection without improvement despite
appropriate antibiotics, antiviral therapy and/or other treatment). Patients with
Epstein-Barr virus (EBV) viremia related to their lymphoma are permitted
• No concurrent malignancy requiring active therapy within the last 3 years with the
exception of basal cell carcinoma limited to the skin, squamous cell carcinoma limited
to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer.
Adjuvant hormonal therapy for cancer previously treated for curative intent is
permitted
• Patients must have documented left ventricular ejection fraction of >= 45%
• No significant active cardiac disease within the previous 6 months including:
• New York Heart Association (NYHA) class III or IV congestive heart failure
• Unstable angina or angina requiring surgical or medical intervention; and/or
• Myocardial infarction
• No contraindication to any drug in the chemotherapy regimen, including neuropathy >=
grade 2
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this
study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days
prior to registration on the study. Chronic concomitant treatment with strong CYP3A4
inducers is not allowed. Patients must discontinue the drug 14 days prior to the start
of study treatment
Testing the Addition of Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in People With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery
This phase III trial compares the effect of adding whole brain radiotherapy with hippocampal
avoidance and memantine to stereotactic radiosurgery versus stereotactic radiosurgery alone
in treating patients with cancer that has spread to the brain and come back in other areas of
the brain after earlier stereotactic radiosurgery. Hippocampus avoidance during whole-brain
radiation therapy decreases the amount of radiation that is delivered to the hippocampus,
which is a brain structure that is important for memory. The medicine memantine is also often
given with whole brain radiation therapy because it may decrease the risk of side effects of
radiation on thinking and memory. Stereotactic radiosurgery delivers a high dose of radiation
only to the small areas of cancer in the brain and avoids the surrounding normal brain
tissue. Adding whole brain radiotherapy with hippocampal avoidance and memantine to
stereotactic radiosurgery may be effective in shrinking or stabilizing cancer that has spread
to the brain and returned in other areas of the brain after receiving stereotactic
radiosurgery.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04588246
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Inclusion Criteria:
• Patients must have developed their first or second distant brain relapse(s) at least 8
weeks after upfront SRS and within 21 days prior to randomization
• Distant brain relapse lesions to be treated must measure =< 3.0 cm in maximal
extent and total volume of distant brain relapses to be treated must measure < 30
mL on the contrast-enhanced diagnostic magnetic resonance imaging (MRI) brain
scan obtained within 21 days prior to randomization
• Distant brain relapse lesions must be diagnosed on MRI, which will include the
following elements:
• REQUIRED MRI ELEMENTS
• Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D)
spoiled gradient (SPGR). Acceptable 3D SPGR sequences include
magnetization-prepared 3D gradient recalled echo (GRE) rapid gradient
echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (brain volume
imaging) or 3D fast FE (field echo). The T1-weighted 3D scan should use
the smallest possible axial slice thickness, not to exceed 1.5 mm
• Pre-contrast T1 weighted imaging (3D imaging sequence strongly
encouraged)
• A minimum of one axial T2 fluid attenuated inversion recovery (FLAIR)
(preferred) or T2 sequence is required. This can be acquired as a 2D or
3D image. If 2D, the images should be obtained in the axial plane
• ADDITIONAL RECOMMENDATIONS
• Recommendation is that an axial T2 FLAIR (preferred) sequence be
performed instead of a T2 sequence
• Recommendation is that that pre-contrast 3D T1 be performed with the
same parameters as the post-contrast 3D T1
• Recommendation is that imaging be performed on a 3 Tesla (3T) MRI
• Recommendation is that the study participants be scanned on the same
MRI instrument at each time point
• Recommendation is that if additional sequences are obtained, these
should meet the criteria outlined in Kaufmann et al., 2020
• If additional sequences are obtained, total imaging time should not
exceed 60 minutes
• Brain metastasis velocity (BMV) since upfront SRS must be >= 4 brain metastases/year
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
• Pathologically (histologically or cytologically) proven diagnosis of non-small cell
lung cancer, melanoma, breast cancer, renal cell carcinoma, or gastrointestinal cancer
within 10 years prior to randomization. If the original histologic proof of malignancy
is greater than 10 years, then pathological (i.e., more recent) confirmation is
required (e.g., from a systemic metastasis or brain metastasis)
• Other histologies are not permitted
• History and physical examination within 28 days prior to randomization
• Karnofsky performance status of >= 70 within 28 days prior to randomization
• Calculated creatinine clearance (CrCl) >= 30 ml/min (within 28 days prior to
randomization)
• Blood urea nitrogen (BUN) within 1.5 times the institutional upper limit of normal
(ULN) (e.g., if the ULN is 20 mg/dL, then BUN up to 30 mg/dL is permitted) (within 28
days prior to randomization)
• Negative urine or serum pregnancy test (in women of childbearing potential) within 14
days prior to randomization
Exclusion Criteria:
• Prior WBRT or prophylactic cranial irradiation
• Local relapse of metastasis previously treated with upfront SRS (i.e., relapse outside
previously SRS-treated metastases is allowed)
• Brain metastases from primary germ cell tumor, small cell carcinoma, or lymphoma
• Definitive leptomeningeal metastasis
• Planned cytotoxic chemotherapy on the same day as SRS or HA-WBRT; concurrent
immunotherapy is permitted
• Radiographic evidence of enlargement or other architectural distortion of the lateral
ventricles, including placement of external ventricular drain or ventriculoperitoneal
shunt
• Known history of demyelinating disease such as multiple sclerosis
• Inability to swallow pills
• Contraindication to MR imaging such as non-MR conditional implanted metal devices or
unknown metallic foreign bodies, or contraindication to gadolinium contrast
administration during MR imaging, such as anaphylactic allergy that cannot be
adequately addressed with pre-contrast medications or acute kidney injury
• Contraindications to memantine, including:
• Allergy, including prior allergic reaction to memantine
• Intractable seizures on adequate anticonvulsive therapy-more than 1 seizure per
month for the past 2 months
• Current use of N-methyl-D-aspartate (NMDA) agonist
• Current alcohol or drug abuse, which can exacerbate lethargy/dizziness with
memantine
• Severe, active co-morbidity defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of randomization
• Chronic obstructive pulmonary disease exacerbation or other acute respiratory
illness precluding study therapy at the time of randomization
• Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic
disease
• Renal tubular acidosis or metabolic acidosis
• Human immunodeficiency virus (HIV) positive with CD4 count < 200
cells/microliter. Note that patients who are HIV positive are eligible, provided
they are under treatment with highly active antiretroviral therapy (HAART) and
have a CD4 count >= 200 cells/microliter within 30 days prior to randomization.
Note also that HIV testing is not required for eligibility for this protocol
• Pregnant or lactating women, or women of childbearing potential and men who are
sexually active and not willing/able to use medically acceptable forms of
contraception; this exclusion is necessary because the medication and radiation
involved in this study has unknown effects on the unborn fetus
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Metastatic Digestive System Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Metastatic Melanoma, Metastatic Renal Cell Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8, Recurrent Brain Neoplasm, Stage IV Lung Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Brain and Nervous System, Brain/Central Nervous System
Protonix Treatment of Maintenance of Healing in Pediatric Participants Aged 1-11 Years and 12-17 Years
The purpose of this study is to explore the outcomes, tolerability and safety of 2 different
doses of oral pantoprazole (full healing dose, half healing dose), assigned based upon
weight, for the maintenance of healing of erosive esophagitis in pediatric participants aged
1 to 17 years with endoscopically-confirmed, healed erosive esophagitis.
Thomas Ratchford
All
1 Year to 17 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04821310
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Inclusion Criteria:
• Participants must have a documented erosive lesion with an Los Angeles (LA) Grade of A
to D prior to starting Proton Pump Inhibitor treatment:
• Capable of giving signed informed consent/assent
• Willingness and ability of the participant or parent/legal guardian to complete the
eDiary
• Willing and able to comply with all scheduled visits, treatment plan, laboratory
tests, lifestyle considerations, and other study procedures, including the use of the
eDiary.
• Male and female participants aged 1 to 17 years.
• Minimum body weight 7 kilogram and weight at least at the 5th percentile per the
Center for Disease Control standard age and weight chart, for the participant's age.
• To be considered a female of non childbearing potential, the participant must meet at
least 1 of the following criteria :
• Premenarchal: The investigator (or other appropriate staff) must discuss the
participant's premenarchal status with the participant and parent/legal guardian at
office visits and during telephone contacts, as participants who achieve menarche
during the study would no longer be considered "female participants of non
childbearing potential" and must comply with the protocol requirements applicable to
women of childbearing potential.
Exclusion Criteria:
• Previous administration of an investigational drug or vaccine within 30 days (or as
determined by the local requirement) or 5 half-lives preceding the first dose of study
intervention used in this study (whichever is longer).
• Children that may be at high risk from procedural sedation should be carefully
evaluated. Participants with a history of complications during prior procedural
sedation
• History or presence of upper gastrointestinal anatomic or motor disorders
• Family history of malignant hyperthermia
• Known hypersensitivity to any Proton Pump Inhibitor, including pantoprazole or to any
substituted benzimidazole or to any of the excipients.
• Any disorder requiring chronic (daily) use of warfarin, heparin, other anticoagulants,
methotrexate, atazanavir or nelfinavir, clopidogrel, or potent inhibitors or inducers
of CYP2C19 (eg, phenytoin, sulfamethoxazole, valproic acid, carbamazepine, and
griseofulvin).
• Serum creatine kinase levels >3 x upper limit of normal.
• Known history of human immunodeficiency virus or clinical manifestations of acquired
immune deficiency syndrome.
• Active malignancy of any type, or history of a malignancy. Participants with a history
of malignancies that have been surgically removed or eradicated by irradiation or
chemotherapy and who have no evidence of recurrence for at least 5 years before
Screening are acceptable.
• Diagnosed as having or has received treatment for esophageal, gastric, pyloric
channel, or duodenal ulceration within 30 days before the Screening visit.
• Alanine aminotransferase or blood urea nitrogen >2.0 upper limit of normal or
estimated creatinine >1.5 X upper limit of normal for age or any other laboratory
abnormality considered by the Investigator to be clinically significant within 14 days
before the Baseline Visit (Day 1).
• Other acute or chronic medical or psychiatric condition including recent (within the
past year) or active suicidal ideation or behavior or laboratory abnormality that may
increase the risk associated with study participation or study intervention
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the participant inappropriate for entry into
this study.
• Has, in the Investigator's opinion, a serious chronic condition (eg, diabetes,
epilepsy), which is either not stable or not well controlled and may interfere with
the conduct of the study.
• Has any condition possibly affecting drug absorption (eg, gastrectomy).
Prior or Concomitant Therapy:
• Frequent, repeated use of oral or parenteral glucocorticoids (eg, prednisone,
prednisolone, dexamethasone). Steroid inhalers and topical steroids may be used.
• Pregnant female participants; breastfeeding female participants.
• Is unwilling or unable to comply with the Lifestyle Considerations section
A Multi-center, Single-arm Trial Exploring the Safety and Clinical Effectiveness of RBX2660 Administered by Colonoscopy to Adults With Recurrent Clostridioides Difficile Infection (CDI-SCOPE)
This trial will be initiated to explore whether RBX2660 (REBYOTA®) could be suitable for
administration by the practice of colonoscopy. More specifically, the purpose of this trial
is to explore the safety and clinical effectiveness of RBX2660 when delivered by colonoscopy
to adults with rCDI. The experience of physicians will be documented through a
physician-experience questionnaire to explore the usability of RBX2660 in clinical practice
for colonoscopic administration. Furthermore, to explore the patient-experience of RBX2660
treatment, each trial participant will be offered to undergo a structured interview.
Nasia Safdar, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05831189
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Inclusion Criteria:
• have documented evidence of rCDI (≥1 recurrence after a primary CDI episode)
• be undergoing antibiotic treatment for the qualifying rCDI episode that was diagnosed
by a stool test for the presence of toxigenic C. difficile or C. difficile toxin
• be eligible for FMT as judged by the investigator or current treatment guidelines for
rCDI in the US
• be a candidate for colonoscopy as judged by the investigator
Exclusion Criteria:
• Use or planned use of systemic antibiotics for an indication other than the qualifying
rCDI episode.
• Current uncontrolled chronic diarrhea not related to CDI.
• Receipt of CDI vaccine or treatment with CDI monoclonal antibodies within the past 12
months before screening.
• Evidence of active, severe, or fulminant colitis, diagnosis of toxic megacolon or have
a current colostomy or ileostomy
Clostridium Difficile Infection Recurrence, Enterocolitis due to Clostridium difficile, Other, Infections, Immune System & Allergies, Digestive Health & Liver Disease
Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (QUIC)
This is a phase 2 study of gemcitabine, cisplatin, zimberelimab (AB122) and quemliclustat
(AB680) in subjects with untreated advanced biliary tract cancers (BTC). The study will
include a safety run-in involving 6 study participants. The goal of the safety run-in is to
screen for early safety signals of the proposed drug combination. Trial enrollment can
continue while full safety assessment is being completed for the first 6 subjects.
Participants will receive 4 cycles of combination therapy as described. After 4 cycles (~6
months), cisplatin will be discontinued, while gemcitabine, zimberelimab (AB122), and
quemliclustat (AB680) will be continued. Subjects will be treated until disease progression
or development of intolerable toxicities. In total, there will be up to 39 participants on
the study.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT06048133
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Inclusion Criteria:
1. Patients with cytologically or histologically confirmed BTC by AJCC version 8.
2. Patients must have late stage (locally advanced, recurrent or metastatic) BTC.
Patients must not have received systemic treatment for advanced disease. Prior
adjuvant therapy is allowed as long as recurrences occurred 6 months or later from all
treatment completion.
3. Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.
4. Age ≥ 18 years at the time of consent.
5. ECOG Performance Status of 0-2 within 28 days prior to registration.
6. Presence of measurable or evaluable disease, as defined by RECIST v1.1.
7. Adequate organ function as detailed in the protocol.
8. Females of childbearing potential who are sexually active with a male able to father a
child must have a negative pregnancy test (serum or urine) within 14 days prior to
registration.
9. Females of childbearing potential who are sexually active with a male able to father a
child must be willing to abstain from heterosexual vaginal intercourse or use an
effective method(s) of contraception from the time of informed consent, during the
study and for up to 120 days after the last dose of study drug(s). Males able to
father a child must be willing to abstain from heterosexual vaginal intercourse or to
use an effective method(s) of contraception from initiation of treatment, during the
study and for up to 120 days after the last dose of study drug(s). See the protocol
for specific timeframes for each drug.
10. Ability of the subject to understand and comply with study procedures for the entire
length of the study, as determined by the enrolling physician or protocol designee.
Exclusion Criteria:
1. Prior therapy with gemcitabine, cisplatin, or any immune checkpoint inhibitors for the
treatment of BTC.
2. Known hypersensitivity to recombinant proteins, or any excipient contained in
treatment medication formulations.
3. Active autoimmune disease that has required systemic treatment in the past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
NOTE: participants with asthma who require intermittent use of bronchodilators,
inhaled corticosteroids, or local corticosteroid injections will not be excluded from
this study.
4. History of solid organ or allogeneic bone marrow transplantation.
5. Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the
mother is being treated on study.
6. Patients with a prior or concurrent malignancy whose natural history or treatment has
the potential to interfere with the safety or efficacy assessment of the
investigational regimen are not eligible for this trial.
7. Untreated central nervous system (CNS) metastasis. Screening of asymptomatic patients
for CNS metastasis is not required for enrollment.
8. Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will
make the administration of IP(s) hazardous, including but not limited to
• Interstitial lung disease, including history of interstitial lung disease or
non-infectious pneumonitis.
• Active viral, bacterial, or fungal infections requiring parenteral treatment
within 14 days of the initiation of the study treatments.
9. History of trauma or major surgery within 28 days prior to the first dose of IP. (Note
that placement of central venous access catheter (e.g., port or similar) is not
considered a major surgical procedure.
10. Treatment with palliative radiation therapy within 14 days of study treatment
initiation.
11. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
12. Significant dementia or other mental condition that precludes the participant's
ability to consent to the study.
13. Use of any live vaccines against infectious diseases within 4 weeks (28 days) of
initiation of investigational products.
Other Digestive Organ, Gastrointestinal cancers, other, Biliary Tract Carcinoma, Cholangiocarcinoma, Bile Duct Cancer
CA-4948 Added to Standard Chemotherapy to Treat Metastatic or Unresectable Pancreatic Cancer
This phase I trial tests the safety, side effects, and best dose of emavusertib (CA-4948) in
combination with gemcitabine and nab-paclitaxel in treating patients with pancreatic ductal
adenocarcinoma that has spread from where it first started (primary site) to other places in
the body (metastatic) or cannot be removed by surgery (unresectable). CA-4948 is in a class
of medications called kinase inhibitors. It works by blocking the action of abnormal proteins
called interleukin-1 receptor-associated kinase 4 (IRAK4) and FMS-like tyrosine kinase 3
(FLT3) that signal cells to multiply. This may help keep cancer cells from growing. The usual
approach for patients with pancreatic ductal adenocarcinoma is treatment with chemotherapy
drugs gemcitabine and nab-paclitaxel. Gemcitabine is a chemotherapy drug that blocks the
cells from making DNA and may kill cancer cells. Paclitaxel is in a class of medications
called anti-microtubule agents. It stops cancer cells from growing and dividing and may kill
them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which
may have fewer side effects and work better than other forms of paclitaxel. Giving CA-4948 in
combination with gemcitabine and nab-paclitaxel may shrink or stabilize metastatic or
unresectable pancreatic ductal adenocarcinoma.
Monica Patel
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05685602
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Inclusion Criteria:
• Patients must have histologically or cytologically confirmed adenocarcinoma of the
pancreas that is metastatic or unresectable and for which standard curative or
palliative measures do not exist or are no longer effective
• Patients must have had disease progression on or after fluorouracil (5-FU)-based
therapy for metastatic or unresectable pancreatic ductal adenocarcinoma (PDAC). If
received gemcitabine-based regimen as adjuvant therapy, then gemcitabine and
nab-paclitaxel (if used) should be >12 months from study enrollment. Prior use of
gemcitabine/nab-paclitaxel for metastatic or unresectable disease is not allowed
• Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of CA-4948 in combination with gemcitabine and nab-paclitaxel 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
• Glomerular filtration rate (GFR) >= 60 mL/min (based on the calculated Chronic Kidney
Disease Epidemiology Collaboration [CKD-EPI] glomerular filtration rate estimation)
• Creatine phosphokinase (CPK) elevation at the screening < grade 2 (creatine
phosphokinase [CPK] =< 2.5 ULN)
• Patients on a cholesterol lowering statin must be on a stable dose with no dose
changes within 3 weeks prior to study start
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial as
long as their anti-retroviral therapy does not have the potential for drug-drug
interactions as judged by the treating investigator
• 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 if follow-up brain imaging after
at least 4 weeks following central nervous system (CNS)-directed therapy shows no
evidence of progression
• 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
• Patients must have lesions amenable to research biopsy for those enrolling to the
expansion cohort. The biopsy should be deemed feasible and safe for pre-biopsy lesion
assessment criteria
• The effects of CA-4948, nab-paclitaxel, and gemcitabine on the developing human fetus
are unknown. For this reason and because gemcitabine is known to be teratogenic,
embryotoxic, and fetotoxic in mice and rabbits, women of child-bearing potential and
men must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry, for the duration of study participation,
and 6 months after completion of CA-4948, nab-paclitaxel, and gemcitabine
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. Men treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and 3
months after completion of CA-4948, nab-paclitaxel, and gemcitabine administration
• 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 chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study
• Patients who have not recovered from clinically significant adverse events due to
prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the
exception of alopecia
• History of other malignancy with the exception of 1) malignancies for which all
treatment was completed at least 2 years before registration and the patient has no
evidence of disease; 2) or known indolent malignancies that do not require treatment
and will likely not alter the course of treatment of disease under treatment
• History of allogeneic organ or stem cell transplant
• Current use or anticipated need for alternative, holistic, naturopathic, or botanical
formulations used for the purpose of cancer treatment
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to CA-4948 or other agents used in study
• Patients receiving any medications or substances that are inhibitors or inducers of
CYP3A4 are ineligible due to CA-4948 and nab-paclitaxel. 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 gemcitabine is nucleoside analogue
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 gemcitabine, breastfeeding should be discontinued if the
mother is treated with gemcitabine. These potential risks may also apply to other
agents used in this study
• Prolonged Fridericia's correction formula (QTcF) (> 470 in females, > 450 in males) on
screening electrocardiogram (ECG)
• Gastrointestinal condition which could impair absorption of CA-4948 or inability to
ingest CA-4948
• Severe obstructive pulmonary disease or interstitial lung disease
• History of rhabdomyolysis or elevated creatine phosphokinase (CPK)
Metastatic Pancreatic Ductal Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Unresectable Pancreatic Ductal Adenocarcinoma, Pancreas
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
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.
Kenneth Desantes, M.D.
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
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
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 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
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, Breast Cancer, Ovarian Cancer, Pancreas Cancer, Prostate Cancer
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 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):
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):
1. Cohort 1: Patients with Pancreatic Ductal Adenocarcinoma (PDAC).
• Pathologically confirmed PDAC with a documented mutation in KRAS.
• Received only 1 prior line of systemic therapy in the advanced or metastatic
setting.
2. Cohort 2: Patients with Non-Small Cell Lung Cancer (NSCLC)
• Pathologically confirmed NSCLC with a documented mutation in KRAS, NRAS,
NF1, or BRAF.
• Received at least 2 prior lines but no more than 4 prior lines of systemic
therapy in the advanced or metastatic setting.
3. Cohort 3: Patients with Colorectal Cancer (CRC)
• Pathologically confirmed CRC with a documented mutation in KRAS, NRAS, NF1,
or BRAF.
• Received at least 2 prior lines of systemic therapy in the advanced or
metastatic setting.
4. Cohort 4: Patients with Melanoma
• Pathologically confirmed melanoma with a documented mutation in NRAS.
• Received at least 1 but not more than 2 prior lines of systemic therapy in
the advanced or metastatic setting that included T-cell checkpoint
inhibitor-based therapy.
• Have not received prior MEK inhibitor therapy.
5. 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 an 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 (eg, 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
8. Systemic venous thrombotic events
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
Pancreatic Ductal Adenocarcinoma, Non-Small Cell Lung Cancer, Colorectal Cancer, Melanoma, Advanced Solid Tumor, Metastatic 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, 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
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
A Study to Characterize the Safety, Tolerability, and Preliminary Efficacy of CFT1946 as Monotherapy and in Combination With Trametinib 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).
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: Receipt of a 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 known human immunodeficiency virus (HIV) infection (with exceptions)
12. Subject has history of or known HBV or active HCV infection
13. Subject has concurrent administration of strong CYP3A4/5 inhibitors and inducers,
including any herbal medications/supplements
14. Subject has presence of Grade ≥2 toxicity due to prior cancer therapy, excepting
alopecia and hypothyroidism requiring thyroid replacement therapy
15. 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
16. 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, Malignant Solid Neoplasm, 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
A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152) (SKYSCRAPER-14)
The purpose of this study is to assess the efficacy and safety of tiragolumab, an anti-TIGIT
monoclonal antibody, when administered in combination with atezolizumab and bevacizumab as
first-line treatment, in participants with unresectable, locally advanced or metastatic
hepatocellular carcinoma (HCC).
Jeremy Kratz, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05904886
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by
histology/cytology or clinically by American Association for the Study of Liver
Diseases (AASLD) criteria in cirrhotic participants
• Disease that is not amenable to curative surgical and/or locoregional therapies
• No prior systemic treatment for locally advanced or metastatic and/or unresectable HCC
• Measurable disease according to RECIST v1.1
• ECOG Performance Status of 0 or 1 within 7 days prior to randomization
• Child-Pugh Class A within 7 days prior to randomization
• Adequate hematologic and end-organ function
• Female participants of childbearing potential must be willing to avoid pregnancy
within 5 months after the final dose of atezolizumab, within 6 months after the final
dose of bevacizumab, and within 90 days after the final dose of tiragolumab/placebo
• Male participants with a female partner of childbearing potential or pregnant female
partner must remain abstinent or use a condom during the treatment period and for 6
months after the final dose of bevacizumab and for 90 days after the final dose of
tiragolumab/placebo to avoid exposing the embryo.
Exclusion Criteria:
• Pregnancy or breastfeeding within 5 months after the final dose of atezolizumab,
within 6 months after the final dose of bevacizumab, and within 90 days after the
final dose of tiragolumab/placebo
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies
• Treatment with investigational therapy within 28 days prior to initiation of study
treatment
• Treatment with locoregional therapy to liver within 28 days prior to initiation of
study treatment, or non-recovery from side effects of any such procedure
• Treatment with systemic immunostimulatory agents
• Treatment with systemic immunosuppressive medication
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or
that are at high risk for bleeding
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior
to initiation of study treatment
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography (CT) scan
• History of malignancy other than HCC within 5 years prior to screening, with the
exception of malignancies with a negligible risk of metastasis or death
• Mixed histology or other subtypes/variants of HCC, including, but not limited to,
known liver adenocarcinoma, fibrolamellar HCC, sarcomatoid HCC, other rare HCC
variant, or mixed cholangiocarcinoma and HCC
• Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
• Acute Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV
infection
• Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases.
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