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.
Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
This phase III trial compares the effect of usual treatment of chemotherapy and steroids and
a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a
Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to
grow and spread. The information gained from this study may help researchers determine if
combination therapy with steroids, TKIs, and blinatumomab work better than the standard of
care.
Ryan Mattison, MD
All
18 Years to 75 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04530565
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Inclusion Criteria:
• ELIGIBILITY CRITERIA FOR PREREGISTRATION (TO STEP 0)
• Patient must be >= 18 and =< 75 years of age
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
between 0-3
• Patient must be newly diagnosed with B-ALL or is suspected to have ALL
• Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the
presence of BCR-ABL translocation must be confirmed centrally. Patients can be
registered and begin Step 1 therapy while awaiting central laboratory eligibility
confirmation
• NOTE: Bone marrow aspirate and/or peripheral blood specimen must be
submitted to the American College of Radiology Imaging Network (ECOG-ACRIN)
Leukemia Laboratory at MD Anderson Cancer Center to determine patient's
eligibility for registration to Step 1 or confirm patient evaluability.
Centrally fluorescence-activated cell sorting (FACS) analysis will be
performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or
acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined
by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia
Laboratory will forward results within 48 hours of receipt of the specimen
to the submitting institution. Bone marrow aspirate is to be from first pull
(initial or re-direct). Specimens must contain sufficient blast cells. In
cases where the bone marrow aspiration may be inadequate, or the bone marrow
examination has already been performed prior to study consent and enrollment
on Step 0, peripheral blood may be submitted, given that adequate
circulating blasts are present (> 10%). If a diagnosis of BCR-ABL positive
B-ALL has already been established by local Clinical Laboratory Improvement
Act (CLIA) certified laboratories, the patient may be registered to Step 1
without waiting for central confirmation
• Patient must not have a diagnosis of BCR/ABL T-ALL
• Patient must not have received chemotherapy for B-ALL. Patients who received up to
five days of hydroxyurea or steroids of any kind with the aim to reduce disease burden
prior to study registration to Step 1 are eligible
• Patients who started any kind of TKI prior to study registration to Step 1 are allowed
to proceed on the study if they received no more than 14 days of TKI
• Patient must not have unstable epilepsy that requires treatment
• Patients with lymphoid blast crisis CML are not eligible
• ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
• Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has
been determined locally and bone marrow and/or peripheral blood was sent and receipt
confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia
Laboratory at MD Anderson Cancer Center
• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn
fetus and possible risk for adverse events in nursing infants with the treatment
regimens being used. All patients of childbearing potential must have a blood test or
urine study within 14 days prior to registration to rule out pregnancy. A patient of
childbearing potential is defined as any woman, regardless of sexual orientation or
whether they have undergone tubal ligation, who meets the following criteria: 1) has
achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral
oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer
therapy does not rule out childbearing potential) for at least 24 consecutive months
(i.e., has had menses at any time in the preceding 24 consecutive months)
• Patients must not expect to conceive or father children by using accepted and
effective method(s) of contraception or by abstaining from sexual intercourse from the
time of step 1 registration, while on study treatment, and until at least six months
after the last dose of study treatment
• Total bilirubin =< 3 mg/dL (patients with Gilbert's syndrome must have a total
bilirubin =< 5 mg/dL) (obtained =< 28 days prior to step 1 registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 X the institutional upper limit of normal (ULN) (obtained =< 28 days prior to
step 1 registration)
• Estimated creatinine clearance > 45 mL/min (based on Cockcroft-Gault equation)
(obtained =< 28 days prior to step 1 registration)
• Patients with acute organ dysfunction at step 1 registration, which may be attributed
to leukemia can be registered regardless of lab results at presentation. Such patients
will be allowed to register and can start Arm A steroid + TKI therapy but will only be
allowed to proceed to Step 2 randomization if the eligibility criteria outlined is met
• Patients who presented with no evidence of acute organ dysfunction but during Step 0
experienced a rise in liver enzymes which investigator suspects to be a side effect of
any of prescribed drugs, are allowed to be registered regardless of the level of liver
enzymes. Step 2 Randomization must be withheld until the eligibility criteria outline
is met but no more than 14 days after concluding Arm A therapy
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable or on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have an undetectable
HCV viral load and if indicated, on treatment
• Patients with a prior malignancy whose natural history or treatment does not have the
potential to interfere with the safety or efficacy assessment of the investigational
regimen are eligible for this trial
• Patient must not have active concomitant malignancy. Patients on chronic hormonal
therapy for breast or prostate cancer or patients treated with maintenance with
targeted agents but are in remission with no evidence for the primary malignancies are
eligible
• 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 must be class 2B or better. An ECHO/MUGA is
required.
• Investigators must confirm which TKI patient is to receive
• NOTE: Patients with known T315I mutation status should receive ponatinib
treatment
• NOTE: In situations due to insurance coverage issues and the pre-selected TKI is
not immediately available, patients can receive dasatinib or imatinib during Step
1. The investigator must re-specify dasatinib or ponatinib prior to Step 2
randomization and from then on patients must receive the pre-selected TKI only
• ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2
• Patient must have completed at least 7 and no more than 21 days of protocol-treatment
on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for
any reason are not counted)
• NOTE: First day of steroids prescription after registration will be considered as
the first day of study therapy. The selected TKI must be initiated prior to
randomization
• Patients who presented with acute organ dysfunction within 2 weeks of registration to
step 1 must have total bilirubin =< 2 X institutional upper limit of normal (ULN)
• AST(SGOT)/ ALT(SGPT) =< 2 X the institutional upper limit of normal (ULN)
• Estimated creatinine clearance > 45 mLg/min (based on Cockcroft-Gault equation)
• Investigators must confirm which TKI patient is to receive.
• NOTE: Patients with known T315I mutation status should receive ponatinib
treatment
• For patients under age 70, intended chemotherapy regimen must have been determined
prior to randomization
• Patient must not have active central nervous system (CNS) involvement by leukemic
blasts. Patients with signs of CNS involvement at presentation are eligible for
randomization if clearance of blasts from the cerebrospinal fluid (CSF) is
demonstrated
• Patients must have resolved any serious infectious complications related to therapy
• Any significant medical complications related to therapy must have resolved
• ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION)
• Institution has received centralized MRD results confirming positive status
• Patients who presented with acute organ dysfunction within 2 weeks of registration to
step 1 must have total bilirubin =< 2 X institutional ULN
• Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =<
2 X institutional upper limit of normal (ULN)
• Patients who presented with acute organ dysfunction must have an estimated creatinine
clearance > 45 mL/min (based on Cockcroft-Gault equation)
• Investigators must confirm which TKI patient is to receive
• NOTE: Patients with known T315I mutation status should receive ponatinib
treatment
• For patients under age 70 and previously assigned to Arm C, intended chemotherapy
regimen must have been determined
• Step 3 (Re-Induction): Patients must have resolved any serious infectious
complications related to therapy
• Step 3 (Re-Induction): Any significant medical complications related to therapy must
have resolved
Exclusion Criteria:
• Patient must not have complaints of symptoms and/or have clinical and/or radiological
signs that indicate an uncontrolled infection or any other concurrent medical
condition that could be exacerbated by the treatment or would seriously complicate
compliance with the protocol
B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1, Lymphoid Leukemia, Leukemia
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 Cabozantinib and Nivolumab in Metastatic Castration Resistant Prostate Cancer (CANOPY)
This is a multicenter, single-arm, two-stage open-label phase 2 study of the combination of
cabozantinib + nivolumab in subjects with advanced castration-resistant prostate cancer
(CRPC).
Christos Kyriakopoulos, MD
Male
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05502315
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Inclusion Criteria:
Subjects must meet all of the following applicable inclusion criteria to participate in
this study:
• Willing and able to provide, or have a legally authorized representative provide,
written informed consent and HIPAA authorization for the release of personal health
information. A signed informed consent must be obtained before screening procedures
are performed. NOTE: HIPAA authorization may be either included in the informed
consent or obtained separately.
• Males 18 years of age and above.
• Histological or cytological proof of prostate adenocarcinoma.
• ECOG status of ≤ 2
• Progressive mCRPC as defined: 1) castrate levels of serum testosterone < 50 ng/dL AND
2) progressive disease as defined by PSA or radiographic progression. Subjects with
measurable and non-measurable disease (i.e., bone only metastases) are allowed. NOTE:
ENROLLMENT of subjects with non-measurable disease (i.e., bone only metastases) will
be capped at 50% of enrollment target (n=25).
• Must have exposure to one prior taxane (or be taxane ineligible or refuse taxane) AND
one prior AR-targeting agent (for example, abiraterone, enzalutamide, apalutamide,
darolutamide). Receipt of taxane or AR-targeting agent may be in the hormone sensitive
or castration resistant setting.
• Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior
treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive
therapy.
• Normal organ function with acceptable initial laboratory values within 14 days of
treatment start:
• WBC: ≥ 2,500/mcL
• ANC: ≥ 1,500/mcL
• Hemoglobin: ≥ 9 g/dL (transfusions are permitted)
• Platelet count: ≥ 100,000/mcL
• Serum creatinine or calculated Creatinine Clearance: Serum creatinine ≤ 1.5 x ULN
or calculated CrCl ≥ 30 mL/min as defined by Cockcroft-Gault equation
• Total Bilirubin: ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert's
disease)
• SGOT (AST): ≤ 3 x ULN
• SGPT (ALT): ≤ 3 x ULN
• Alkaline Phosphatase (ALP): ≤ 5 x ULN with documented bone metastases
• Serum Albumin: ≥ 2.8 g/dL
• Urine protein/creatinine ratio (UPCR): ≤ 2 mg/mg (≤ 113.2 mg/mmol), or 24-h urine
protein ≤ 2 g
• Subjects must agree to use a medically acceptable method of birth control as outlined
in the protocol
• HIV-positive with negative viral loads on stable antiretroviral regimen will be
considered eligible. Subjects must have CD4 count > 350.
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
• Small cell or neuroendocrine component or histology.
• Prior cabozantinib or checkpoint inhibitor.
• Receipt of any type of small molecule kinase inhibitor (including investigational
kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or investigational systemic anti-cancer
agent within 4 weeks before first dose of study treatment.
• Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment
initiation. Treatment with investigational prostate cancer directed therapy within 4
weeks of treatment initiation. Treatment with enzalutamide within 4 weeks of treatment
initiation.
• Receipt of more than 1 line of chemotherapy (including both hormone sensitive and
CRPC). First-generation anti-androgen use (such as bicalutamide) will not be tabulated
as a line of therapy.
• Administration of a live, attenuated vaccine within 30 days prior to first dose of
study treatment.
• Active autoimmune disease or condition requiring prednisone >10 mg daily (or
equivalent). Physiologic replacement is permitted. Topical, ocular, intra-articular
steroids or inhaled corticosteroids are permitted.
• Imminent or established spinal cord compression based on clinical and/or imaging
findings.
• Radiation therapy within 1 week of study treatment start.
• Known brain metastases or cranial epidural disease unless adequately treated with
radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks
prior to first dose of study treatment.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan.
• Malabsorption syndrome.
• Requirement for hemodialysis or peritoneal dialysis.
• History of solid organ or allogenic stem cell transplant.
• Active hepatitis B/C or positive TB test with active mycobacterial infection requiring
systemic treatment.
• Active treatment (within 5 days of registration) with coumarin agents (e.g.,
warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor
betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the
following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable
guidelines) and low-dose molecular weight heparins (LMWH).
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors
rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who
are on a stable dose of the anticoagulant for at least 1 week before first dose
of study treatment without clinically significant hemorrhagic complications from
the anticoagulation regimen or the tumor.
• The subject has uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable
angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm
Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive
treatment.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction
(MI), or other ischemic event, or thromboembolic event (e.g., deep venous
thrombosis, pulmonary embolism) within 6 months before first dose of study
treatment.
• Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6
months are allowed if stable, asymptomatic, and treated with a stable dose
of permitted anticoagulation (see exclusion criterion above) for at least 1
week before first dose of study treatment.
• Gastrointestinal (GI) disorders including those associated with a high risk of
perforation or fistula formation
• The subject has evidence of tumor invading the GI tract, active peptic ulcer
disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis,
cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis,
acute obstruction of the pancreatic duct or common bile duct, or gastric
outlet obstruction.
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal
abscess within 6 months before first dose of study treatment. Note: Complete
healing of an intra-abdominal abscess must be confirmed before first dose of
study treatment.
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon
(2.5ml) of red blood, or other history of significant bleeding (e.g., pulmonary
hemorrhage) within 12 weeks before first dose of study treatment.
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease
manifestation.
• Lesions invading or encasing any major blood vessels.
• Other clinically significant disorders that would preclude safe study
participation.
• Serious non-healing wound/ulcer/bone fracture.
• Uncompensated/symptomatic hypothyroidism.
• Moderate to severe hepatic impairment (Child-Pugh B or C).
• Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of
brain metastasis) within 2 weeks before first dose of study treatment. Minor
surgeries within 10 days before first dose of study treatment. Subjects must have
complete wound healing from major surgery or minor surgery before first dose of
study treatment. Subjects with clinically relevant ongoing complications from
prior surgery are not eligible.
• Corrected QT interval calculated by Fridericia formula (QTcF) >500 ms per
electrocardiogram (ECG) within 14 days before first dose of study treatment [add
reference for Fridericia formula]. NOTE: If a single ECG shows a QTcF with an
absolute >500 ms, two additional ECGs at intervals of approximately 3 min must be
performed within 30 min after the initial ECG, and the average of these three
consecutive results for QTcF will be used to determine eligibility.
• Any other active malignancy at time of first dose of study treatment or diagnosis
of another malignancy within 3 years prior to first dose of study treatment that
requires active treatment, except for locally curable cancers that have been
apparently cured, such as basal or squamous cell skin cancer or superficial
bladder cancer.
• Known allergy to any of the compounds under investigation.
• Inability to swallow tablets.
Prostate, Castration-resistant Prostate Cancer, Metastatic Cancer
Study to Evaluate the Safety and Efficacy of Oral NRC-2694-A in Combination With Paclitaxel in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma, Who Progressed on or After Immune Checkpoint Inhibitor Therapy
This is a Phase 2, open-label, multicenter, single-arm study of NRC-2694-A in combination
with paclitaxel in patients with R/M HNSCC with progression on or after ICI therapy.
A total of approximately 46 male and female patients will be enrolled. This sample size is
based on Simon's 2-stage design with historical control ORR of 30% and a target ORR of 50%.
Justine Bruce, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05283226
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Inclusion Criteria:
• Is willing and capable of understanding the written informed consent, provides signed
and witnessed written informed consent, and agrees to comply with protocol
requirements.
• Is male or female aged 18 years or older at the time of consent.
• Has histologically confirmed unresectable R/M HNSCC (oral cavity, oropharynx,
hypopharynx, and larynx).
• Has documented radiographical progressive disease assessed by the principal
investigator per RECIST v1.1.
• Has a measurable lesion per RECIST v1.1.
• Has ECOG performance status score of ≤2.
• Must have progressed during or after receiving ICI therapy, such as pembrolizumab or
nivolumab. Patients with prior immune-mediated reactions due to ICI therapies (eg,
pembrolizumab or nivolumab) and who had recovered prior to study entry will also be
eligible.
• Female patients of childbearing potential should have a negative urine test before
enrollment. If the urine pregnancy test is positive or gives equivocal results, a
serum pregnancy will be required for confirmation.
• Patients of reproductive age must use acceptable methods of contraception throughout
the study period and for 30 days following the last dose of investigational product
(see protocol for further guidance).
• During screening and at subsequent visits, the investigator should ensure adequate
bone marrow reserve (neutrophil count ≥1500/mm3, platelet count ≥100,000/mm3, and
hemoglobin level 8.0 g/dL), renal function (creatinine clearance ≥50 mL/min calculated
by Cockcroft-Gault formula), liver function (total bilirubin level ≤1.5 × ULN [except
patients with documented Gilbert's syndrome] and serum transaminase levels ≤2.5 × ULN
or ≤5 × ULN for liver metastasis and/or obstructive jaundice).
• Must have completed a duration of at least 4 weeks after stopping ICI therapy and must
have recovered to grade ≤1 from all toxicities due to this therapy.
Exclusion Criteria:
• Has cardiac, hepatic, endocrine, pulmonary, or autoimmune disease, interstitial lung
disease, renal or psychiatric disorders, not controlled with therapy corresponding to
the illness or a condition that contraindicates the use of a taxane or an EGFR
inhibitor.
• Has uncontrolled brain metastases. Patients are allowed if brain metastasis has been
previously treated with surgery, whole brain irradiation, and/or stereotactic
radiosurgery and are considered controlled (controlled by the dose ≤10 mg/day of
prednisone or equivalent) at the time of the first dose of investigational product.
Radiological evaluation of brain metastasis will be performed only if the patient has
symptoms. For asymptomatic patients, brain imaging during screening is not required.
• Has baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc
interval >480 milliseconds [CTCAE Grade 1] using Fredericia's QT correction formula).
• Has a history of additional risk factors for Torsade de pointes (eg, heart failure,
hypokalemia, family history of long QT syndrome).
• Has had prior cetuximab therapy for recurrent or metastatic disease. Note that
cetuximab used concomitantly with radiotherapy or as an induction therapy is
acceptable
• Has received any other EGFR-targeted therapies for recurrent or metastatic disease.
• Currently participating in any clinical trial or receiving investigational therapy on
expanded access or compassionate basis.
• Has nasopharyngeal carcinomas or salivary gland cancers.
• Has received investigational products or any other salvage therapy after failure of
pembrolizumab/nivolumab therapy.
• Female patient who tested positive for pregnancy.
• Female patient who is breastfeeding or planning to become pregnant, or male patient
planning to father a child within the duration of the study.
• Has tested positive for HIV, HBsAg, HCV antibody, or HCV RNA at screening. However,
patients who test positive for HCV antibody, but negative for HCV RNA, will be
allowed. In addition, patients with controlled HIV, chronic HBV on suppressive
antiviral therapy, or a history of HCV infection status post-curative antiviral
treatment with an HCV viral load below limit of quantification are permitted to
participate (DHHS 2020).
• Has active infection requiring intravenous anti-infective therapy within 7 days prior
to Day 1 Cycle 1 or is febrile due to infection.
• Has had major surgery within 4 weeks prior to screening.
• Administered a live attenuated vaccine within 4 weeks prior to Day 1 Cycle 1 or
anticipation that such a live attenuated vaccine will be required during the study.
• Has known or suspected hypersensitivity to any components of the formulation used for
this investigational product.
• Has concurrent disease or any clinically significant abnormality following the
investigator's review of the screening physical examination findings, 12-lead ECG
results, and clinical laboratory tests, which in the judgment of the investigator
would interfere with the patient's participation in this study or evaluation of study
results.
• Unable to come for study visits per schedule.
• Has current drug or alcohol abuse.
• Has received prior treatment with paclitaxel or docetaxel for metastatic or recurrent
HNSCC. However, prior paclitaxel or docetaxel as a component of a curatively-intended
multimodality treatment for locally advanced HNSCC is permitted.
Carcinoma, Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma, Lip, Oral Cavity and Pharynx, Head and Neck
A Study of Baricitinib (LY3009104) in Children From 6 Years to Less Than 18 Years of Age With Alopecia Areata (BRAVE-AA-PEDS)
The main purpose of this study is to determine the efficacy and safety of baricitinib for the
treatment of severe or very severe alopecia areata (hair loss) in children from 6 years to
less than 18 years of age.
The study is divided into 4 periods, a 5-week Screening period, a 36-week Double-Blind
Treatment Period, an approximately 2-year Long-term Extension Period, and a 4-week
Post-treatment Follow-up period.
Lisa Arkin
All
6 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05723198
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Inclusion Criteria:
• Enrollment will be fully sequential by age group, with adolescents (12 to less than 18
years old) enrolling before children (6 to less than 12 years old).
• Have severe areata alopecia (AA) for at least 1 year
• Diagnosis for at least 1 year
• Current AA episode of at least 6 months' duration
• SALT score ≥50% at screening and baseline
• History of trial and failure with at least 1 available treatment (topical or other)
for AA
• History of psychological counseling related to AA
• Current episode of severe AA of less than 8 years.
• Note: Participants who have severe AA for ≥8 years may be enrolled if episodes of
regrowth, spontaneous or under treatment, have been observed on the affected
areas over the past 8 years.
Exclusion Criteria:
• Primarily "diffuse" type of AA (characterized by diffuse hair shedding).
• Are currently experiencing other forms of alopecia including, but not limited to
trichotillomania, telogen effluvium, chemotherapy-induced hair loss, or any other
concomitant conditions (for example, tinea capitis, psoriasis, lupus erythematosus, or
secondary syphilis) that would interfere with evaluations of the effect of study
medication on AA.
• Are largely or wholly incapacitated permitting little or no self-care, such as being
bedridden
• Have uncontrolled arterial hypertension
• Have had major surgery within 8 weeks prior to screening or will require major surgery
during the study
• Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal,
endocrine, hematological, neurological, or neuropsychiatric disorders or any other
serious and/or unstable illness that, in the opinion of the investigator, could
constitute an unacceptable risk when taking IP or interfere with the interpretation of
data.
• Have a positive test for hepatitis B virus (HBV) infection
• Have hepatitis C virus (HCV) infection (positive for anti hepatitis C antibody with
confirmed presence of HCV ribonucleic acid [RNA]).
• Have evidence of human immunodeficiency virus (HIV) infection and/or positive HIV
antibodies.
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
Melanoma Margins Trial-II: 1cm v 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma (MelMarT-II)
Patients with a primary invasive melanoma are recommended to undergo excision of the primary
lesion with a wide margin. There is evidence that less radical margins of excision may be
just as safe. This is a randomised controlled trial of 1 cm versus 2 cm margin of excision of
the primary lesion for adult patients with stage II primary invasive cutaneous melanomas
(AJCC 8th edition) to determine differences in disease-free survival. A reduction in margins
is expected to improve patient quality of life.
Heather Neuman, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03860883
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Inclusion Criteria:
1. Patients must have a stage II primary invasive cutaneous melanoma with Breslow
thickness >2mm without ulceration), or >1mm (with ulceration only) (pT2b-pT4b, AJCC
8th edition) as determined by diagnostic biopsy (narrow excision, incision or punch
biopsy) and subsequent histopathological analysis.
2. Must have a primary melanoma that is cutaneous (including head, neck, trunk,
extremity, scalp, palm or sole).
3. An uninterrupted 2cm margin must be technically feasible around biopsy scar or primary
melanoma.
4. Surgery (which refers to the staging sentinel node biopsy and wide local excision as
these are both to be done on the same day) must be completed within 120 days of the
original diagnosis.
5. Patients must be 18 years or older at time of consent.
6. Patient must be able to give informed consent and comply with the treatment protocol
and follow-up plan.
7. Life expectancy of at least 5 years from the time of diagnosis, not considering the
melanoma in question, as determined by the PI.
8. Patients must have an ECOG performance score between 0 and 1.
9. A survivor of prior cancer is eligible provided that ALL of the following criteria are
met and documented:
• The patient has undergone potentially curative therapy for all prior
malignancies,
• There has been no evidence of recurrence of any prior malignancies for at least
FIVE years (except for successfully treated cervical or non-melanoma skin cancer
with no evidence of recurrence), and
• The patient is deemed by their treating physician to be at low risk of recurrence
from previous malignancies.
Exclusion Criteria:
Patients will be excluded from the study for ANY of the following reasons:
1. Uncertain diagnosis of melanoma i.e. so-called 'melanocytic lesion of unknown
malignant potential'.
2. Patient has already undergone wide local excision at the site of the primary index
lesion.
3. Patient unable or ineligible to undergo staging sentinel lymph node biopsy of the
primary index lesion.
4. Desmoplastic or neurotropic melanoma: with any patient where pathology determines
melanoma as PURE desmoplastic (as per WHO definition of >90% desmoplasia), they are
not eligible for this study. However other desmoplasia or mixed subtypes are eligible
unless there is neurotropism present (peri-neural invasion).Peri-neural invasion does
not include entrapment of nerves within the main primary tumour mass.
Microsatellitosis as per AJCC 8th edition definition
5. Subungual melanoma
6. Patient has already undergone a local flap reconstruction of the defect after excision
of the primary and determination of an accurate excision margin is impossible.
7. History of previous or concurrent (i.e., second primary) invasive melanoma.
8. Melanoma located distal to the metacarpophalangeal joint; on the tip of the nose; the
eyelids or on the ear; genitalia, perineum or anus; mucous membranes or internal
viscera.
9. Physical, clinical, radiographic or pathologic evidence of satellite, in-transit,
regional, or distant metastatic melanoma.
10. Patient has undergone surgery on a separate occasion to clear the lymph nodes of the
probable draining lymphatic field, including sentinel lymph node biopsy, of the index
melanoma.
11. Any additional solid tumour or hematologic malignancy during the past 5 years except
T1 skin lesions of squamous cell carcinoma, basal cell carcinoma, or uterine/cervical
cancer.
12. Melanoma-related operative procedures not corresponding to criteria described in the
protocol.
13. Planned adjuvant radiotherapy to the primary melanoma site after Wide Local Excision
is not permitted as part of the protocol and any patients given this treatment would
be excluded from the study.
14. History of organ transplantation.
15. Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at
enrolment or within 6 months prior to enrolment.
Pregnancy is not a specific exclusion criterion for this trial, though it may not be
clinically appropriate to perform a wide excision and sentinel node biopsy until the
pregnancy has been completed, which is likely to exclude the patient due to violation of
inclusion criterion 4. We would advise careful counselling of the patient prior to
enrolling the patient, which would include a discussion at the treating centre's
multidisciplinary team meeting or tumour board. We would strongly advise contacting the
central trial office to discuss the case prior to enrolling on the study.
Cutaneous Melanoma, Stage II, Melanoma, Skin, Melanoma/Skin cancer
A Study of Camizestrant in ER+/HER2- Early Breast Cancer After at Least 2 Years of Standard Adjuvant Endocrine Therapy (CAMBRIA-1)
This is a Phase III open-label study to assess if camizestrant improves outcomes compared to
standard endocrine therapy in patients with ER+/HER2 - early breast cancer with intermediate
or high risk for disease recurrence who completed definitive locoregional therapy (with or
without chemotherapy) and standard adjuvant endocrine therapy (ET) for at least 2 years and
up to 5 years. The planned duration of treatment in either arm of the study is 60 months.
Kari Wisinski, MD
All
18 Years to 130 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05774951
Show full eligibility criteria
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Inclusion Criteria:
• Women and Men, ≥18 years at the time of screening (or per national guidelines)
• Histologically confirmed ER+/HER2- early-stage resected invasive breast cancer with
high or intermediate risk of recurrence, based on clinical-pathological risk features,
as defined in the protocol.
• Completed adequate (definitive) locoregional therapy (surgery with or without
radiotherapy) for the primary breast tumour(s), with or without (neo)adjuvant
chemotherapy
• Completed at least 2 years but no more than 5 years (+3 months) of adjuvant ET (+/-
CDK4/6 inhibitor)
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Adequate organ and marrow function
Exclusion criteria:
• Inoperable locally advanced or metastatic breast cancer
• Pathological complete response following treatment with neoadjuvant therapy
• History of any other cancer (except non-melanoma skin cancer or carcinoma in situ of
the cervix or considered at very low risk of recurrence per investigator judgement)
unless in complete remission with no therapy for a minimum of 5 years from the date of
randomisation
• Any evidence of severe or uncontrolled systemic diseases which, in the investigator's
opinion precludes participation in the study or compliance
• Known LVEF <50% with heart failure NYHA Grade ≥2.
• Mean resting QTcF interval >480 ms at screening
• Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for
non-cancer-related conditions
• Any concurrent anti-cancer treatment not specified in the protocol with the exception
of bisphosphonates (e.g. zoledronic acid) or RANKL inhibitors (eg, denosumab)
• Previous treatment with camizestrant, investigational SERDs/investigational ER
targeting agents, or fulvestrant
• Currently pregnant (confirmed with positive serum pregnancy test) or breastfeeding
• Patients with known hypersensitivity to active or inactive excipients of camizestrant
or drugs with a similar chemical structure or class to camizestrant. In
pre-/peri-menopausal female and male patients, known hypersensitivity or intolerance
to LHRH agonists, that would preclude the patient from receiving any LHRH agonist
Combining Biomarkers and Electronic Risk Scores to Predict AKI in Hospitalized Patients
The study's objective is to evaluate the additive value of renal biomarkers (from blood and
urine) for identifying individuals at high risk for severe acute kidney injury (AKI) above
that of a novel natural language processing (NLP)-based AKI risk algorithm. The risk
algorithm is based on electronic health records (EHR) data (labs, vitals, clinical notes, and
test reports). Patients will enroll at the University of Chicago Medical Center and the
University of Wisconsin Hospital, where the risk score will run in real time. The risk score
will identify those patients with the highest risk for the future development of Stage 2 AKI
and collect blood and urine for biomarker measurement over the subsequent 3 days.
Matthew Churpek
All
18 Years and over
IV
This study is NOT accepting healthy volunteers
NCT05988658
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Inclusion Criteria:
1. Age ≥ 18 years
2. E-STOP AKI 2.0 score in the top 10% of risk (historically from all hospitalized
patients) within the last 12 hours. (First time across this 10% risk threshold during
this hospital stay).
3. Admitted to an inpatient ward, intermediate, or ICU care at the University of Chicago
Medical Center (UCMC) or University of Wisconsin Health (UWHealth). (No Emergency
Department patients)
4. Patient or their legally authorized representative must be able to read, speak, and
understand English, for the purposes of consenting. Otherwise, inclusion in this
protocol will be done without regard to race, ethnic origin or gender
Exclusion Criteria:
1. Voluntary refusal or missing written consent of the patient / legal representative.
2. Patients with a known history of end-stage renal disease on dialysis (including renal
transplantation).
3. Patients without a measured serum creatinine value during their inpatient stay.
4. Patients with a creatinine >4.0 mg/dl at the time of admission or available in the EHR
from the last 6 months
5. Patients with prior episode of KDIGO defined AKI during this same hospitalization-
regardless of E-STOP AKI 2.0 score
6. Patients with prior renal consultation during their admission.
7. Patient with an E-STOP AKI 2.0 above the top 10% risk threshold more than 12 hours ago
during this same hospital stay.
8. Incarcerated patients
9. Pregnant patients
A Phase 3 Randomized, Masked, Controlled Trial to Evaluate Efficacy and Safety of Belzupacap Sarotalocan (AU-011) Treatment Compared to Sham Control in Subjects With Primary Indeterminate Lesions or Small Choroidal Melanoma (CoMpass)
The primary objective is to determine the safety and efficacy of belzupacap sarotalocan
(bel-sar) compared to sham control in patients with primary indeterminate lesions (IL) or
small choroidal melanoma (CM).
Michael Altaweel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT06007690
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Inclusion Criteria:
• Clinical diagnosis of primary indeterminate lesion or small choroidal melanoma (IL/CM)
• Have no evidence of metastatic disease confirmed by imaging
• Be treatment naive for IL/CM (subjects who received PDT may be eligible)
Exclusion Criteria:
• Have known contraindications or sensitivities to the study drug or laser
• Active ocular infection or disease
Ramucirumab Plus Pembrolizumab vs Usual Care for Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer Following Immunotherapy, Pragmatica-Lung Study
This phase III trial compares the effect of the combination of ramucirumab and pembrolizumab
versus standard of care chemotherapy for the treatment of non-small cell lung cancer that is
stage IV or that has come back after a period of improvement (recurrent). Ramucirumab is a
monoclonal antibody that may prevent the growth of new blood vessels that tumors need to
grow. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's
immune system attack the cancer, and may interfere with the ability of tumor cells to grow
and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. This trial may help doctors find out if giving ramucirumab with pembrolizumab is
more effective at treating patients with stage IV or recurrent non-small cell lung cancer
than standard chemotherapy.
Kari Wisinski, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05633602
Show full eligibility criteria
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Inclusion Criteria:
• Participants must have histologically or cytologically confirmed non-small cell lung
cancer (NSCLC) which is stage IV or recurrent
• Participants must have received at least one line of anti-PD-1 or anti-PD-L1 therapy
for any stage of NSCLC. Anti-PD-1 or anti-PD-L1 may have been given alone or in
combination with other therapy
• Participants must have experienced disease progression (in the opinion of the treating
physician) more than (>) 84 days following initiation (cycle 1 day 1) of their most
recent anti-PD-1 or PD-L1 therapy
• Participants who received anti-PD-1 or anti-PD-L1 therapy for stage IV or recurrent
disease, must have had a best response on anti-PD-1 or anti-PD-L1 therapy of stable,
partial response or complete response (in the opinion of the treating physician)
• Participants who received neoadjuvant, adjuvant, and/or consolidation anti-PD-1 or
anti-PD-L1 therapy as their only line of anti-PD-1 or anti-PD-L1 therapy must have
experienced disease progression within (=<) 365 days from initiation (cycle 1 day 1)
of anti-PD-1 or PD-L1 therapy
• Participants must have received platinum-based chemotherapy and experienced disease
progression (in the opinion of the treating physician) during or after this regimen
• Participants with a known sensitizing mutation for which an Food and Drug
Administration (FDA)-approved targeted therapy for NSCLC exists (e.g., EGFR, ALK,
ROS1, BRAF, RET, NTRK, KRAS, HER2 and MET sensitizing mutations), must have previously
received at least one of the approved therapy(s). Prior targeted therapy for
participants with targetable alterations is allowed if all other eligibility criteria
are also met
• Participants must be >= 18 years old
• Participants must be able to safely receive the investigational drug combination and
the investigator's choice of standard of care regimens per the current FDA approved
package insert(s), treating investigator's discretion, and institutional guidelines
• Participants must have Zubrod performance status of 0-2
Exclusion Criteria:
• Participants must not have received more than one line of anti-PD-1 or anti-PD-L1 for
stage IV or recurrent disease
• Participants must not be receiving or planning to receive another investigational
therapy during study participation
Recurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Lung
A Study to Compare Standard Therapy to Treat Hodgkin Lymphoma to the Use of Two Drugs, Brentuximab Vedotin and Nivolumab
This phase III trial compares the effect of adding immunotherapy (brentuximab vedotin and
nivolumab) to standard treatment (chemotherapy with or without radiation) to the standard
treatment alone in improving survival in patients with stage I and II classical Hodgkin
lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates.
It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent
called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and
delivers vedotin to kill them. A monoclonal antibody is a type of protein that can bind to
certain targets in the body, such as molecules that cause the body to make an immune response
(antigens). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's
immune system attack the cancer, and may interfere with the ability of tumor cells to grow
and spread. Chemotherapy drugs such as doxorubicin hydrochloride, bleomycin sulfate,
vinblastine sulfate, dacarbazine, and procarbazine hydrochloride 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. Cyclophosphamide is in a class of medications called
alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill
cancer cells. It may also lower the body's immune response. Etoposide is in a class of
medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell
division and DNA repair and may kill cancer cells. Vincristine is in a class of medications
called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may
kill them. Prednisone is in a class of medications called corticosteroids. It is used to
reduce inflammation and lower the body's immune response to help lessen the side effects of
chemotherapy drugs. Radiation therapy uses high energy x-rays to kill tumor cells and shrink
tumors. Adding immunotherapy to the standard treatment of chemotherapy with or without
radiation may increase survival and/or fewer short-term or long-term side effects in patients
with classical Hodgkin lymphoma compared to the standard treatment alone.
Priyanka Pophali
All
5 Years to 60 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05675410
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Inclusion Criteria:
• Patients must be 5 to 60 years of age at the time of enrollment
• Patients with newly diagnosed untreated histologically confirmed classic Hodgkin
lymphoma (cHL) (nodular sclerosis, mixed cellularity, lymphocyte-rich, or
lymphocyte-depleted, or not otherwise specified [NOS]) with stage I or II disease
• Patients must have bidimensionally measurable disease (at least one lesion with
longest diameter >= 1.5 cm)
• Patients must have a whole body or limited whole body PET scan performed within 42
days prior to enrollment. PET-CT is strongly preferred. PET-MRI allowed if intravenous
contrast enhanced CT is also obtained
• Pediatric patients (age 5-17 years) must have an upright posteroanterior (PA) chest
X-ray (CXR) for assessment of bulky mediastinal disease. Adult patients must have
either a CXR or CT chest
• Patients >= 18 years must have a performance status corresponding to Zubrod scores of
0, 1 or 2
• Patients =< 17 years of age must have a Lansky performance score of >= 50
• Pediatric patients (age 5-17 years): A serum creatinine based on age/gender as follows
(within 7 days prior to enrollment):
• 2 to < 6 years (age): 0.8 mg/dL (male), 0.8 mg/dL (female)
• 6 to < 10 years (age): 1 mg/dL (male), 1 mg/dL (female)
• 10 to < 13 years (age): 1.2 mg/dL (male), 1.2 mg/dL (female)
• 13 to < 16 years (age): 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years (age): 1.7 mg/dL (male), 1.4 mg/dL (female) OR a 24 hour urine
creatinine clearance >= 50 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR
a glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2 (within 7 days prior to
enrollment). 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 or plasma creatinine, cystatin C or other
estimates are not acceptable for determining eligibility
• For adult patients (age 18 years or older) (within 7 days prior to enrollment):
Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or
a 24-hour urine collection. The creatinine value used in the calculation must have
been obtained within 28 days prior to registration. Estimated creatinine clearance is
based on actual body weight
• Total bilirubin =< 2 x upper limit of normal (ULN) (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing
bile duct syndrome
• Aspartate aminotransferase (AST) =< 3 x ULN (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing
bile duct syndrome
• Alanine aminotransferase (ALT) =< 3 x ULN (within 7 days prior to enrollment)
• Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing
bile duct syndrome
• Shortening fraction of >= 27% by echocardiogram (ECHO), multigated acquisition scan
(MUGA), or functional cardiac imaging scan (within 7 days prior to enrollment) or
ejection fraction of >= 50% by radionuclide angiogram, ECHO, MUGA, or cardiac imaging
scan (within 7 days prior to enrollment)
• Diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted value as
corrected for hemoglobin by pulmonary function test (PFT) (within 7 days prior to
enrollment). If unable to obtain PFTs, the criterion is: a pulse oximetry reading of >
92% on room air
• Known human immunodeficiency virus (HIV)-infected patients on effective
anti-retroviral therapy with undetectable viral load within 6 months are eligible for
this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated. Patients with a
history of hepatitis C virus (HCV) infection must have been treated and cured. For
patients with HCV infection who are currently on treatment, they are eligible if they
have an undetectable HCV viral load
Exclusion Criteria:
• Patients with nodular lymphocyte predominant Hodgkin lymphoma
• Patients with a history of active interstitial pneumonitis or interstitial lung
disease
• Patients with a diagnosis of inherited or acquired immunodeficiency that is poorly
controlled or requiring active medications, such as primary immunodeficiency syndromes
or organ transplant recipients
• Patients with any known uncontrolled intercurrent illness that would jeopardize the
patient's safety such as infection, autoimmune conditions, cardiac arrhythmias, angina
pectoris, and gastrointestinal disorders affecting swallowing and/or absorption of
pills
• Patients with a condition requiring systemic treatment with either corticosteroids
(defined as equivalent to > 10 mg daily prednisone for patients >= 18 years or > 0.5
mg/kg [up to 10 mg/day] for patients < 18 years) or other immunosuppressive
medications within 14 days prior to enrollment
• Note: Replacement therapy such as thyroxine, insulin, or physiologic
corticosteroid for adrenal or pituitary insufficiency is not considered a form of
systemic treatment. Inhaled or topical steroids, and adrenal replacement doses
(=< 10 mg daily for patients >= 18 years or =< 0.5 mg/kg [up to 10 mg/day]
prednisone equivalents) are permitted in the absence of active autoimmune disease
• Note: Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but
must be discontinued by cycle 1, day 1
• Patients with peripheral neuropathy > grade 1 at the time of enrollment or patients
with known Charcot-Marie-Tooth syndrome
• 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
• Administration of prior chemotherapy, radiation, or antibody-based treatment for cHL
• Prior solid organ transplant
• Prior allogeneic stem cell transplantation
• Live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g., measles,
mumps, rubella, varicella, yellow fever, rabies, bacillus calmette guerin [BCG], oral
polio vaccine, and oral typhoid). Administration of messenger ribonucleic acid (mRNA)
vaccines are permitted
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test within 28 days prior to
enrollment is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants starting with the first dose of
study therapy and for at least 6 months after the last treatment
• Sexually active patients of reproductive potential who have not agreed to use a highly
effective contraceptive method (failure rate of < 1% per year when used consistently
and correctly) for the duration of their study drug therapy. Following therapy,
patients will be advised to use contraception as per institutional practice or as
listed below for investigational agents, whichever is longer
• Men and women of childbearing potential must continue contraception for a period
of 6 months after last dose of brentuximab vedotin
• Women of child-bearing potential (WOCBP) must continue contraception for a period
of at least 5 months after the last dose of nivolumab
• 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
This clinical trial will investigate an estrogen-regulated parameter as an early measure of
endocrine therapy response: progesterone receptor (PR) protein with a progestin-based
radioligand, 18F-fluorofuranylnorprogesterone (18F-FFNP). The overall purpose of this
research is to test the efficacy of 18F-FFNP PET/MRI for predicting response to presurgical
endocrine therapy and to determine the quantitative reliability of 18F-FFNP breast PET/MRI in
patients with newly diagnosed ER+/PR+/HER2- primary breast cancer.
Amy Fowler, MD, PhD
Female
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT06086704
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Inclusion Criteria:
• Postmenopausal status defined by either
• prior bilateral oophorectomy
• age greater than or equal to 60 years of age
• age less than 60 years of age and amenorrheic for 12 or more months in the
absence of prior chemotherapy, tamoxifen, toremifene or ovarian suppression and
FSH and estradiol in the postmenopausal range per local normal range
• Diagnosis of biopsy-proven invasive breast cancer measuring at least 1.0 cm in
diameter by any imaging modality
• Biopsy-proven ER-positive, PR-positive, HER2-negative invasive breast cancer
• Breast MRI planned or performed before surgery
• Definitive surgical excision of the primary tumor planned without neoadjuvant therapy;
defined as therapy (chemotherapy, targeted therapy, radiation therapy or endocrine
therapy) given to decrease the size of the tumor prior to planned surgery.
Exclusion Criteria:
• Inability or unwillingness to provide informed consent to the study
• PR and Ki67 IHC slides or FFPE tissue blocks from clinical breast biopsy not available
• Patients who have completed neoadjuvant chemotherapy, endocrine therapy, targeted
therapy, surgical resection, or radiation for the current biopsy-proven malignancy
• Patients who are planning to undergo anastrozole as standard of care neoadjuvant
therapy
• Patients who are currently taking aromatase inhibitors or ER antagonists (tamoxifen,
raloxifene)
• Patients with breast expanders
• Patients who are pregnant or lactating
• Patients whose girth exceeds the bore of the PET/MRI scanner
• Patients with a contraindication to gadolinium-based contrast agents, including
allergy or impaired renal function (per UW Health Guidelines)
• Patients with a history of allergic reaction attributable to compounds of similar
chemical or biologic composition to 18F-FFNP
• Patients with history of allergic reaction to anastrozole
• Patients in liver failure as judged by the patient's physician
• Patients with standard contraindications to MRI (per UW Health Guidelines)
• Patients requiring conscious sedation for imaging are not eligible; patients requiring
mild, oral anxiolytics for the clinical MRI scan will be allowed to participate as
long as the following criteria are met:
• The patient has their own prescription for the medication
• The informed consent process is conducted prior to the self-administration of the
medication.
• The patient comes to the research visit with a driver.
• Patients unable to lie prone for 45 minutes for imaging
• Patients taking hormone replacement therapy or over-the-counter
products/supplements/herbal preparation with potential estrogenic effects who are
unwilling to discontinue these agents during the timeframe of the study until surgery.
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
Safety and Efficacy of PC945 (Opelconazole) in Combination With Other Antifungal Therapy for the Treatment of Refractory Invasive Pulmonary Aspergillosis (OPERA-T Study)
To assess the safety and efficacy of nebulized PC945 in combination with systemic antifungal
therapy for the treatment of refractory IPA
Alexander Lepak, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05238116
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Inclusion Criteria:
1. Participant has proven or probable IPA according to the modified 2019 European
Organization for Research and Treatment of Cancer/ Mycoses Study Group Education and
Research Consortium (EORTC/MSGERC) consensus definitions or according to the 2010
International Society for Heart and Lung Transplantation (ISHLT) consensus statements
for the definitions of infections in cardiothoracic transplant recipients.
2. Participant's IPA has failed to respond to adequate antifungal therapy.
Exclusion Criteria:
1. Participant with a known or suspected concomitant medical condition or post-surgery
complication that, in the opinion of the Investigator, may jeopardize adherence to the
protocol requirements or impede the accurate measurement of efficacy or may be an
unacceptable additional risk to the Participant should he/she participate in the
study.
2. Participant who has previously received PC945.
3. Participant with a known history of allergy, hypersensitivity, or any previous serious
reaction to any component of the PC945 or placebo formulations.
4. Participant who has recently received, is receiving or due to receive at any time
during the study, an investigational medicinal agent that does not have any regulatory
approved indications. Subjects who are participating in any other trials e.g.,
Observational, diagnostic or using medications with an approved indication may be
allowed to participate after consultation with the sponsor on an individual basis
Pembrolizumab vs. Observation in People With Triple-negative Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Pembrolizumab
The phase III trial compares the effect of pembrolizumab to observation for the treatment of
patients with early-stage triple-negative breast cancer who achieved a pathologic complete
response after preoperative chemotherapy in combination with pembrolizumab. Immunotherapy
with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack
the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial
may help researchers determine if observation will result in the same risk of cancer coming
back as pembrolizumab after surgery in triple-negative breast cancer patients who achieve
pathologic complete response after preoperative chemotherapy with pembrolizumab.
Malinda West, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05812807
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Inclusion Criteria:
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Triple Negative Breast Cancer:
• Patients with a history of stage T1cN1-2 or T2-4N0-2 breast cancer according to
the primary tumor-regional lymph node anatomic staging criteria of the American
Joint Committee on Cancer (AJCC), 8th edition as determined by the investigator
in radiologic assessment, clinical assessment or both
• Patients must have no residual invasive disease in the breast or lymph nodes
after the completion of neoadjuvant therapy. Residual ductal carcinoma in situ
(DCIS) is allowed. Isolated tumor cells are considered node-negative
• Estrogen (ER) and progesterone (PR) =< 10%; HER2-negative by American Society of
Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
(immunohistochemistry [IHC] and fluorescence in situ hybridization [FISH])
• If invasive disease was present in both breasts, participation in the study is
permitted as long as the eligibility criteria are met for both tumors/breasts
• Patients must have received neoadjuvant chemotherapy in combination with pembrolizumab
for a minimum of 6 cycles. All systemic chemotherapy and ICI therapy should have been
completed preoperatively
• An interval of no more than 12 weeks between the completion date of the final surgery
and the date of randomization
* Note: Adjuvant radiation can be given on study. If given, it is encouraged to be
given concurrently with pembrolizumab, per investigator discretion. Treatment with
adjuvant pembrolizumab is strongly discouraged prior to participation in this trial,
but if administered (e.g., if patients are awaiting pathology results), pembrolizumab
may be administered for up to 6 weeks post-surgery and must be completed prior to
registration
• Use of investigational anti-cancer agents must be discontinued at time of registration
• Adequate excision: Surgical removal of all clinically evident disease in the breast
and lymph nodes as follows:
• Breast surgery: Total mastectomy or breast-conserving surgery with histologically
negative margins, including no ink on tumor for DCIS, at the time of excision
** For patients who undergo breast-conserving surgery, the margins of the
resected specimen must be histologically free of ductal carcinoma in-situ (DCIS)
as determined by the local pathologist. If pathologic examination demonstrates
DCIS at the line of resection, additional operative procedures may be performed
to obtain clear margins. If DCIS is still present at the resected margin after
re-excision(s), the patient must undergo total mastectomy to be eligible.
Patients with margins positive for classic lobular carcinoma in situ (LCIS) are
eligible without additional resection
• Lymph node surgery:
• For a patient with clinically N0 disease, a sentinel lymph node biopsy
should have been performed at time of surgical evaluation, and if
pathologically node positive, the patient is no longer eligible. Isolated
tumor cells are considered node-negative
• For a patient with clinically N1 disease at diagnosis (with positive results
from a fine-needle aspiration, core biopsy, or sentinel node biopsy
performed prior to preoperative therapy) additional surgical evaluation of
the axilla following preoperative therapy is required
*** If they become cN0 (no palpable adenopathy), then a sentinel lymph node
biopsy could have been performed at time of surgery (axillary dissection
would also be permitted); if the sentinel lymph node biopsy is positive, the
patient is no longer eligible
• If sentinel node biopsy performed before preoperative therapy was negative,
no additional surgical evaluation of the axilla is required after
preoperative therapy. If sentinel node biopsy performed before preoperative
therapy was positive, an ALND is required after preoperative therapy
• If the only sentinel node identified by isotope scan is in the internal
mammary chain, surgical evaluation of the axilla is still required
• If sentinel node evaluation after preoperative therapy is negative, no
further additional surgical evaluation of the axilla is required
• Axillary dissection without sentinel node evaluation is permitted as the
initial or sole axillary evaluation after preoperative therapy
• If breast-conserving surgery was performed but patient will not be receiving breast
radiation, the patient is not eligible
• Not pregnant and not nursing, because this study involves an agent whose genotoxic,
mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
Therefore, for women of childbearing potential only, a negative serum or urine
pregnancy test done =< 7 days prior to randomization is required
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Platelet Count >= 100,000/mm^3
• Estimated glomerular filtration rate (eGFR) >= 15 mL/min/1.73m^2
• Total Bilirubin =<1.5 x upper limit of normal (ULN)
* Patients with Gilbert's disease with a total bilirubin =< 2.5 x ULN and direct
bilirubin within normal limits are permitted
• Aspartate aminotransferase (AST) serum aspartate aminotransferase [SGOT] / alanine
aminotransferase (ALT) serum glutamic pyruvic transaminase [SGPT] =< 3 x institutional
ULN
• Patients must be willing to provide tumor tissue from the diagnostic core biopsy. If
inadequate tumor tissue is available, patients are still eligible to participate in
the trial
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months prior to registration are
eligible for this trial
Exclusion Criteria:
• No stage IV (metastatic) breast cancer
• No history of any prior (ipsi- or contralateral) invasive breast cancer. Prior DCIS is
allowed
• No evidence of recurrent disease following preoperative therapy and surgery
• No known active liver disease, e.g. due to hepatitis B virus (HBV), hepatitis C virus
(HCV), autoimmune hepatic disorders, or sclerosing cholangitis
• No history of intolerance, including Grade 3 or 4 infusion reaction or
hypersensitivity to pembrolizumab or murine proteins or any components of the product
* Note: Prior immune-related adverse events (irAEs) are allowed if they resolved and
the patient tolerated subsequent therapy without requiring chronic steroids for the
irAE
• No medical conditions that require chronic systemic steroids (>10 mg prednisone daily
or equivalent) or any other form of immunosuppressive medications and has required
such therapy in the last two years. Replacement therapy (e.g. thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
etc.) is not considered a form of systemic therapy
• Patients who are unable or unwilling to comply with the requirements of the protocol
per investigator assessment are not eligible
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Early Stage Triple-Negative Breast Carcinoma, Breast
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
To Evaluate Efficacy and Safety of Serplulimab + Chemotherapy (Carboplatin- Etoposide) in US Patients With ES-SCLC
This is a randomized, open-label study of Serplulimab plus chemotherapy
(Carboplatin-Etoposide) in comparison with Atezolizumab plus chemotherapy in previously
untreated US patients with ES-SCLC.
Subjects in this study will be randomized to arm A or B at 1:1 ratio as follows:
- Arm A (Serplulimab): Serplulimab + chemotherapy (carboplatin-etoposide)
- Arm B (control): Atezolizumab + chemotherapy (carboplatin-etoposide)
Toby Campbell, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05468489
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Inclusion Criteria:
Voluntary participation in clinical studies.
Male or female aged ≥ 18 years at the time of signing the ICF.
Histologically or cytologically diagnosed with ES-SCLC (according to the Veterans
Administration Lung Study Group staging system).
No prior systemic therapy for ES-SCLC.
At least one measurable lesion as assessed according to RECIST 1.1 within 4 weeks prior to
randomization.
Major organs are functioning well.
Every effort should be made to provide tumor tissues for the determination of PD-L1
expression.
An ECOG PS score of 0 or 1.
An expected survival ≥ 12 weeks.
Subjects with prior denosumab use that can and agree to switch to bisphosphonate therapy
for bone metastases starting prior to randomization and throughout treatment.
Participant must keep contraception.
Exclusion Criteria:
Histologically or cytologically confirmed mixed SCLC.
Known history of severe allergy to any monoclonal antibody.
Known hypersensitivity to carboplatin or etoposide.
Patients with myocardial infarction within half a year before the first dose of the study
drug, poorly controlled arrhythmia.
Pregnant or breastfeeding females.
Patients with a known history of psychotropic drug abuse or drug addiction.
Patients who have other factors that could lead to the early termination of this study
based on the investigator's judgment.
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
A Study to Investigate the Safety and Efficacy of K-321 Eye Drops After Simultaneous Cataract Surgery and Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD)
A study to assess the safety and efficacy of K-321 in participants with FECD after
simultaneous cataract surgery and descemetorhexis.
Evan Warner
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05826353
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Inclusion Criteria:
• Is at least 18 years old at the screening visit (Visit 1)
• Has a diagnosis of FECD at Visit 1
• Meet all other inclusion criteria outlined in the Clinical Study Protocol.
Exclusion Criteria:
• Is a female subject of childbearing potential and any of the following is true:
1. is pregnant or lactating/breastfeeding, or
2. is not surgically sterile, not post-menopausal (no menses for the previous 12
months), or not practicing an effective method of birth control as determined by
the Investigator (eg, oral contraceptives, double barrier methods, hormonal
injectable or implanted contraceptives, tubal ligation, or partner with
vasectomy)
• Meet any other exclusion criteria outlined in the Clinical Study Protocol.
A Study of Alpelisib and Fulvestrant to Treat Endometrial Cancer
This is a 2 stage multi-center study designed to evaluate the efficacy of the combination of
alpelisib and fulvestrant in patients with PIK3CA-mutated ER-positive endometrioid
endometrial cancers by estimating the objective response rate (ORR). Treatment will continue
until either unacceptable toxicity, progression of disease, or investigator/patient request
for withdrawal.
Janelle Sobecki, MD
Female
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05154487
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Inclusion Criteria:
1. Patient must have advanced (FIGO 2014 Stage III or IV), persistent, or recurrent
endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy.
Histologic confirmation of recurrent disease is required. For cases of persistent
disease, histologic confirmation of the primary disease with radiologic evidence of
progression is required.
2. Patients must have endometrioid histology (all grades allowed) based on hysterectomy
or biopsy specimen and have positive expression of ER and oncogenic PIK3CA mutation
per criteria below.
a. PIK3CA mutations considered oncogenic include R88Q, N345K, C420R, E542K, E545X,
Q546X, M1043I, H1047X, or G1049R. The list of oncogenic mutations acceptable for
enrollment may be expanded as further information becomes available.
i. Oncogenic PIK3CA mutations identified on tests performed by the labs listed on
https://ecog-acrin.org/nci-match-eay131-designated-labs will be considered confirmed
for the purposes of this study ii. Oncogenic PIK3CA mutations identified by other
tests will need to be confirmed by the study prior to enrollment b. Estrogen receptor
(ER) status will be considered positive if ≥1% of tumor cells demonstrate positive
nuclear staining by immunohistochemistry. Pathology report documenting ER status must
be provided at enrollment.
Sites are required to report results of previous MMR and/or MSI status testing in
Medidata Rave if available.
3. All patients must have measurable disease. Measurable disease is defined by RECIST
version 1.1. Measurable disease is defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded). Each
lesion must be greater than or equal to 10mm when measured by CT, MRI or caliper
measurement by clinical exam; or greater than or equal to 20mm when measured by chest
x-ray. Lymph nodes must be greater than or equal to 15mm in short axis when measured
by CT or MRI.
Patients must have at least one "target lesion" to be used to assess response on this
protocol as defined by RECIST 1.1. Tumors within a previously irradiated field will be
designated as "non-target" lesions unless progression is documented or a biopsy is
obtained to confirm persistence at least 90 days following completion of radiation
therapy.
4. Prior chemotherapy in the adjuvant setting for Stage I, II, or III is permitted. Prior
chemoradiotherapy for a pelvic recurrence is permitted.
Note: No prior chemotherapy in the setting of Stage IV disease is permitted unless the
patient was without evidence of disease at the completion of chemotherapy and had a
least six months of progression-free survival since the completion of chemotherapy.
Regardless of circumstances, no more than one prior chemotherapy regimen (including
chemo-radiotherapy) is permitted.
Patients who received prior chemotherapy must have recovered (Common Terminology
Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy
except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A
washout period of at least 21 days is required between last chemotherapy dose and
initiation of therapy.
Patients who received radiotherapy must have completed and fully recovered from the
acute effects of radiotherapy. A washout period of at least 14 days is required
between end of radiotherapy and initiation of therapy.
5. Patient must be able to swallow oral medications.
6. Patient must have an ECOG performance status of 0 to 1.
7. Patients must have adequate glucose control as defined by the following (both criteria
must be met):
• Fasting blood glucose (FBG) ≤140/dL (7.7mmol/L) AND
• Hemoglobin A1c (HbA1c) ≤6.4%
8. Patients must have adequate organ and marrow function as defined below NOTE:
Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower
limit of normal = LLN
Bone marrow function:
• Absolute neutrophil count (ANC) greater than or equal to 1500/mcl
• Platelets greater than or equal to 100,000 cells/mcl
• Hemoglobin greater than or equal to 8 g/dL (Patients may receive erythrocyte
transfusions to achieve this hemoglobin level at the discretion of the
investigator. Initial treatment must not begin earlier than the day after
erythrocyte transfusion).
Renal function:
• Creatinine Clearance ≥ 35 mL/min using Cockcroft-Gault formula
Pancreatic function:
• Fasting Serum amylase ≤ 2 × ULN
• Fasting Serum lipase ≤ ULN
Hepatic function:
• Bilirubin less than or equal to 1.5 x ULN (Patients with Gilbert's syndrome with
a total bilirubin ≤2 times ULN and direct bilirubin within normal limits are
permitted).
• ALT (alanine aminotransferase) and AST (aspartate aminotransferase) less than or
equal to 3 x ULN
• Alkaline phosphatase less than or equal to 2.5 x ULN
• Albumin greater than or equal to 2.8 g/dL
9. Patients must have signed an approved informed consent and authorization permitting
release of personal health information.
10. Patients must be at least 18 years of age.
11. Patients of childbearing potential must have a negative serum pregnancy test prior to
the study entry and be practicing a highly effective form of contraception during the
study treatment and for 8 weeks after stopping the treatment.
Highly effective contraception methods include combination of any of the following (oral,
injected, or implanted hormonal contraceptives are prohibited:
• Placement of an intrauterine device (IUD) or intrauterine system (IUS);
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault
caps) with spermicidal foam/gel/film/cream/vaginal suppository;
• Total abstinence or;
• Male/female sterilization. Women are considered post-menopausal and not of
child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea
with an appropriate clinical profile (e.g. age appropriate, history of vasomotor
symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy)
or tubal ligation at least six weeks prior to randomization. In the case of
oophorectomy alone, only when the reproductive status of the woman has been confirmed
by follow up hormone level assessment is she considered not of child-bearing
potential.
Exclusion Criteria:
1. Patients who have previously received any PIK3CA, PI3K, mTOR, or AKT inhibitor.
2. Patients with clear cell, serous, carcinosarcoma, mixed histology endometrial cancers,
or uterine sarcomas.
3. Known intolerance or hypersensitivity to alpelisib or fulvestrant, or any of their
excipients.
4. Patients who have previously received hormonal therapy for endometrial cancer.
5. Participant has had major surgery within 14 days prior to study treatment start and/or
has not recovered from major side effects.
6. Participant with an established diagnosis of diabetes mellitus type I or uncontrolled
type II (based on fasting blood glucose [FBG] and HemoglobinA1c [HbA1c], see INCLUSION
CRITERION 7)
7. Patients with concomitant invasive malignancy or a history of other invasive
malignancies, with the exception of non-melanoma skin cancer, are excluded if there is
any evidence of other malignancy being present within the past five years. Patients
are also excluded if their previous cancer treatment contraindicates this protocol.
8. Patients with active bacterial infection (requiring intravenous [IV] antibiotics at
time of initiating study treatment, fungal infection, or detectable viral infection
(such as known human immunodeficiency virus (HIV) positivity or with known active
hepatitis B or C [for example, hepatitis B surface antigen positive]). Screening is
not required for enrollment.
9. Patients with a serious pre-existing medical condition(s) that would preclude
participation in this study (for example: interstitial lung disease or pneumonitis,
severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (i.e.
estimated creatinine clearance <30ml/min), history of major surgical resection
involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative
colitis or pre-existing chronic condition resulting in baseline grade 2 or higher
diarrhea).
10. Patients with a known history of cardiac disease. This includes:
• Uncontrolled hypertension, defined as systolic greater than 150mm Hg or diastolic
greater than 90mm Hg despite antihypertensive medications
• Myocardial infarction, unstable angina, symptomatic pericarditis, or coronary
artery bypass graft (CABG) within 6 months prior to registration.
• New York Heart Association (NYHA) Class II or greater congestive heart failure.
• History of clinically significant cardiac arrhythmias (i.e. ventricular
tachycardia or ventricular fibrillation, complete left bundle branch block, high
grade AV block (e.g. bifascicular block, Mobitz type II and third degree AV block
without pacemaker in place) or serious cardiac arrhythmia requiring medication.
This does not include asymptomatic atrial fibrillation with controlled
ventricular rate.
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT
syndrome, or Fridericia QT correction formula (QTcF) > 470 msec at screening.
• Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6
months prior to the first date of study therapy.
• Syncope of cardiovascular etiology,
• Sudden cardiac arrest.
11. Participant is currently receiving any of the following medications and cannot be
discontinued 7 days prior to the start of the treatment:
• Strong CYP3A4 inducers
• Inhibitors of BCRP.
12. Patients who are pregnant or breast-feeding.
13. Patients with known central nervous system metastases which was not previously treated
and not fulfilling the following 3 criteria to be eligible for the study:
• Completed prior therapy (including radiation and/or surgery) for CNS metastases ≥
28 days prior to the start of study entry and
• CNS tumor is clinically stable at the time of screening and
• Participant is not receiving steroids and/or enzyme inducing anti-epileptic
medications for brain metastases.
14. Patients with an impairment of gastrointestinal function or gastrointestinal disease
that may significantly alter the absorption of the study drugs (i.e. ulcerative
disease; uncontrolled nausea, vomiting and/or diarrhea; malabsorption syndrome;
clinical signs and symptoms of gastrointestinal obstruction; and/or patients who
require parenteral hydration and/or nutrition).
15. Patients who plan to receive live attenuated vaccines within 1 week of start of
alpelisib and during the study. Patients should also avoid close contact with others
who have received live attenuated vaccines. Examples of live attenuated vaccines
include intranasal influenza, measles, mumps, rubella, oral polio, BCG< yellow fever,
varicella, and TY21a typhoid vaccines.
16. Patients with active bleeding or pathologic conditions that carry high risk of
bleeding such as known bleeding disorder or coagulopathy.
17. Patients who are currently part of or have participated in any clinical investigation
with an investigational drug within 30 days prior to dosing, or within 5 half-lives of
the investigational product, whichever is longer.
18. Patient is not able to understand and to comply with study instructions and
requirements, including oral administration of study treatment.
Endometroid Endometrial Cancer, Corpus Uteri, Uterus
Testing the 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
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Inclusion Criteria:
• PHASE 1: Patients must have a histologically confirmed metastatic or locally advanced
unresectable solid tumor that has progressed on or after available standard of care
therapy or for which no acceptable standard of care therapy exists, or in which the
patient declines standard of care therapy (each patient that declines standard of care
therapy will be documented in the case report form)
• PHASE 2: Patients must have a histologically confirmed metastatic or locally advanced
unresectable cholangiocarcinoma/gallbladder carcinoma that has progressed on at least
1 prior standard of care therapy or for which no acceptable standard of care therapy
exists, or in which the patient declines standard of care therapy (each patient that
declines standard of care therapy will be documented in the case report form)
• Age >= 18 years
• Because no dosing or adverse event data are currently available on the use of
M3814 in combination with avelumab in patients < 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Patients with at least 1 index lesion to irradiate for whom palliative radiation
treatment is indicated (including but not limited to pain and/or symptom control,
prevention of disease -related complications, and preservation of organ function).
Lung and liver lesions are preferred, though alternate lesions may be considered after
discussion with trial principal investigator (PI). Up to 2 lesions may be considered
for irradiation provided at least 1 lesion will receive the study treatment of total
of 60 Gy and all prescribed irradiation will be completed within the radiation window
• Patients with at least 1 Response Evaluation Criteria in Solid Tumors (RECIST)
measurable lesion (to be unirradiated) (defined as those accurately measured in at
least one dimension, with the longest diameter to be recorded for non-nodal lesions
and the shortest diameter for nodal lesions). Measurable is defined as at least 10 mm
in longest diameter for solid tumors, at least 15 mm in shortest diameter for lymph
nodes
• Patients must be willing to undergo fresh biopsies at baseline (as opposed to using
archival tissue), in the event their baseline tissue was obtained > 12 months prior to
study consent and/or they are randomized to the gamma H2AX pNBS1 multiplex IFA assay
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelet count >= 100,000/mcL
• Hemoglobin >= 9.0 g/dL
• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR calculated serum creatinine
clearance (glomerular filtration rate [GFR] can be used in place of creatinine or
creatinine clearance) >= 60 mL/min for participants with creatinine levels > 1.5 x
institutional ULN
• Calculate serum creatinine clearance using the standard Cockcroft-Gault formula
• Serum total bilirubin =< 1.5 x ULN or direct bilirubin =< ULN for participants with
total bilirubin > 1.5 x ULN
• Patients with known Gilbert disease with serum bilirubin level =< 3 x ULN are
eligible
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
ULN or =< 5.0 x ULN for patients with hepatobiliary tumors/liver metastases
• Albumin >= 2.8 g/L
• International normalized ratio (INR) or prothrombin time (PT) or activated partial
thromboplastin time (aPTT) =< 1.5 x ULN
• This applies only to patients not receiving therapeutic anticoagulation; patients
receiving therapeutic anticoagulation should be on a stable dose
• Participants must have the ability to swallow and retain oral medication and not have
any clinically significant gastrointestinal abnormalities that might alter absorption
• Female patients of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required. The effects of M3814 and avelumab on the developing human fetus
are unknown and there is the potential for teratogenic or abortifacient effects. For
this reason, women and men of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry, for the duration of study treatment, and for 6 months after completion of M3814
and avelumab administration. Should a woman become pregnant or suspect she is pregnant
while she or her partner is participating in this study, she should inform her
treating physician immediately. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with M3814 and
avelumab, breastfeeding should be discontinued if the mother is treated with M3814 and
avelumab
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a close caregiver
or legally authorized representative (LAR) and/or family member available will also be
eligible
Exclusion Criteria:
• PHASE I: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other
immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents
• PHASE II: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other
immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents with
the following exceptions:
• Patients who have only received previous durvalumab (anti-PD-L1) in combination
with gemcitabine +/- cisplatin as part of first line therapy (TOPAZ-1 regimen)
are eligible
• Patients who have only received previous pembrolizumab (anti-PD-1) in combination
with gemcitabine +/- cisplatin as part of first line therapy (KEYNOTE-966
regimen) are eligible
• Patients who have had chemotherapy, definitive radiation, biological cancer therapy,
or investigational agent/device within 21 days of first planned dose of study therapy
(within 14 days for palliative radiation). Previously irradiated lesions may be
re-irradiated provided there is disease progression in the irradiated lesion and the
prescribed radiation dosage can safely be re- administered
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > Common Terminology Criteria for Adverse Events
[CTCAE] grade 1) with the exception of alopecia
• Patients with untreated/uncontrolled central nervous system (CNS)/leptomeningeal
disease. Patients with asymptomatic, treated CNS disease are eligible if the treating
physician determines that immediate CNS specific treatment is not required and is
unlikely to be required during the first cycle of therapy and the following criteria
are met:
• Radiographic demonstration of clinical stability upon the completion of
CNS-directed therapy and no evidence of interim progression between the
completion of CNS-directed therapy and the screening radiographic study done >= 4
weeks from completion of radiotherapy and >= 2 weeks from discontinuation of
corticosteroids
• No stereotactic radiation or whole-brain radiation within 28 days prior to
randomization
• Patients with active autoimmune disease requiring systemic corticosteroids greater
than the equivalent of prednisone 10 mg daily including but not limited to: systemic
lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, colitis,
vascular thrombosis associated with antiphospholipid syndrome, Wegener's
granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple
sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis, with the
following exceptions:
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone are eligible
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are
eligible
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
dermatologic manifestations only who require only low potency topical steroids
(e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%,
desonide 0.05%, alclometasone dipropionate 0.05%) are eligible
• Patients receiving treatment with systemic immunosuppressive medications (including,
but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate,
thalidomide, and anti-tumor necrosis factor [TNF] agents) within 6 weeks must
discontinue these medications prior to starting M3814 and avelumab on day 7, with the
exception of:
• Patients with active autoimmune disease managed with systemic corticosteroids
less than the equivalent of prednisone 10 mg daily
• Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea)
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
for patients with orthostatic hypotension and adrenocortical insufficiency
• Patients who have undergone prior solid organ or bone marrow transplant with the
exception of patients with prior renal transplant for whom dialysis may be employed in
the event of graft rejection
• Patients with uncontrolled intercurrent illness (e.g., including but not limited to
uncontrolled hypertension [HTN] [systolic blood pressure (BP) > 150, diastolic BP >
100], symptomatic congestive heart failure [CHF], unstable angina pectoris, ischemic
myocardial infarction [MI] within 6 months, cardiac arrhythmia, recent transient
ischemic attack [TIA or cerebrovascular accident (CVA)]) within 6 months
• Patients with serious active infection (e.g. requiring hospitalization and/or
intravenous [IV] antibiotics) within 4 weeks prior to starting M3814 and avelumab, or
signs/symptoms of infection or receiving oral or IV antibiotics for the treatment of
active systemic infection within 2 weeks prior to starting M3814 and avelumab.
Patients receiving prophylactic antibiotics are eligible
• Patients with known chronic hepatitis B virus (HBV) infection must have an
undetectable viral load on suppressive therapy if indicated. Patients with known
chronic hepatitis C (HCV) infection must have been treated and cured. Patients who are
currently on curative treatment are eligible if they have an undetectable HCV viral
load
• Patients with known human immunodeficiency virus (HIV) are allowed on study provided
they have:
• A stable regimen of highly active anti-retroviral therapy (HAART)
• No requirement for concurrent antibiotics or antifungal agents for the prevention
of opportunistic infection
• A CD4 count above 250 cells/mcL
• An undetectable HIV viral load on standard polymerase chain reaction (PCR)-based
testing
• Patients with history of idiopathic pulmonary fibrosis, pneumonitis (including drug
induced), organizing pneumonia (e.g., bronchiolitis obliterans, cryptogenic organizing
pneumonia), or evidence of active pneumonitis on screening chest computed tomography
(CT) scan
• Patients with known concurrent malignancy that is expected to require active treatment
within two years, or may interfere with the interpretation of the efficacy and safety
outcomes of this study in the opinion of the treating investigator. Superficial
bladder cancer, nonmelanoma skin cancers, and low-grade prostate cancer not requiring
cytotoxic therapy should not exclude participation in this trial. Patients with
chronic lymphocytic leukemia (CLL) may be enrolled if they do not require active
chemotherapy and their hematologic, renal and hepatic function meets criteria
previously mentioned
• Patients with psychiatric illness/social situations that would limit compliance with
study requirements
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to M3814 or avelumab
• Patients unable to discontinue medications or substances that are potent inhibitors,
inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to starting M3814 and
avelumab are ineligible. Medications or substances that are strong inhibitors of
CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first M3814 dose.
Strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the
first dose. Drugs mainly metabolized by CYP3A with a narrow therapeutic index as
judged by the investigator must stop at least 1 day prior to first M3814 dose. Because
the lists of these agents are constantly changing, it is important to regularly
consult a frequently-updated medical reference. As part of the enrollment/informed
consent procedures, the patient will be counseled on the risk of interactions with
other agents, and what to do if new medications need to be prescribed or if the
patient is considering a new over-the-counter medicine or herbal product. The primary
elimination mechanism of avelumab is proteolytic degradation, thus there are no
contraindicated medications with respect to avelumab
• Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs) prior to
starting M3814 and avelumab. These must be discontinued >= 5 days prior to starting
M3814 and avelumab. Patients do not need to discontinue calcium carbonate. H2 blockers
are allowed provided they are taken at least 2 hours after M3814 dose
• Patients receiving sorivudine or any chemically related analogues (such as brivudine)
and not able to discontinue prior to starting M3814 and avelumab are excluded
• Pregnant and lactating women are excluded from this study because M3814 and avelumab
are agents with the potential for teratogenic or abortifacient effects. Because there
is an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with M3814 and avelumab, breastfeeding should be discontinued
if the mother is treated with M3814 and avelumab
• Patients who have received live vaccination within 30 days before starting M3814 and
avelumab
Cholangiocarcinoma, Gallbladder Carcinoma, Stage III Gallbladder Cancer AJCC v8, Stage III Hilar Cholangiocarcinoma AJCC v8, Stage III Intrahepatic Cholangiocarcinoma AJCC v8, Stage IV Gallbladder Cancer AJCC v8, Stage IV Hilar Cholangiocarcinoma AJCC v8, Stage IV Intrahepatic Cholangiocarcinoma AJCC v8, Liver, Other Digestive Organ, Gastrointestinal cancers, other
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression (RECOVER)
Objectives of this study are to determine whether active VNS Therapy treatment is superior to
a no stimulation control in producing a reduction in baseline depressive symptom severity,
based on multiple depression scale assessment tools at 12 months from randomization.
Steven Garlow, MD, PhD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03887715
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Inclusion Criteria:
The patient must be in a major depressive disorder (MDD) episode for ≥ two years or have
had at least four episodes of MDD, including the current episode.
The patient's depressive illness meets a minimum criterion of four prior failed treatments
of adequate dose and duration as measured by a tool designed for this purpose.
The patient is experiencing a major depressive episode (MDE) as measured by a guideline
recommended depression scale assessment tool on two visits, within a 45-day span prior to
implantation of the VNS device.
Patients must maintain a stable medication regimen for at least four weeks before device
implantation.
Exclusion Criteria:
Current or lifetime history of psychotic features in any MDE;
Current or lifetime history of schizophrenia or schizoaffective disorder;
Current or lifetime history of any other psychotic disorder;
Current or lifetime history of rapid cycling bipolar disorder;
Current secondary diagnosis of delirium, dementia, amnesia, or other cognitive disorder;
Current suicidal intent; or
Treatment with another investigational device or investigational drugs.
Treatment Resistant Depression, Bipolar disorder, Major depressive disorder, recurrent, Other
A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Infants (0 to <2 Years of Age) With Achondroplasia
This trial is a Phase 2, multicenter, double-blind, randomized (ratio 2:1 TransCon CNP vs.
placebo), placebo-controlled trial, designed to evaluate the safety, tolerability, and
efficacy of 100 μg CNP/kg of Navepegritide (TransCon CNP) administered SC once-weekly for 52
weeks in infants with genetically verified heterozygous ACH, aged 0 to < 2 years at the time
of randomization.
Janet Legare
All
0 Years to 2 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT06079398
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Inclusion Criteria:
• Written, signed informed consent by the parent(s)/caregiver(s) of the participant, and
as required by the institutional review board/human research ethics
committee/independent ethics committee (IRB/HREC/IEC).
• Male or female younger than 2 years of age at the time of randomization; or for open
label sentinel participants, at the time of first administration of IMP.
• Clinical diagnosis of achondroplasia (ACH) with genetic confirmation of heterozygous
genotype present during screening.
• Parent(s)/caregiver(s) willing to follow the protocol and instructions provided,
including being able to administer weekly subcutaneous injections of trial treatment.
• Compliance to daily Vitamin D supplementation for infants aged 14 days to 1 year. All
participants older than 1 year of age with serum 25-hydroxyvitamin D (25OHD) measured
below lower limit of reference range at screening should start daily Vitamin D
supplementation prior to randomization.
• Considered eligible based on the medical history, physical examination, and the
results of vital signs, ECG, imaging, and clinical laboratory tests performed during
the screening period.
Exclusion Criteria:
• Known or suspected hypersensitivity to the investigational product or related products
(trehalose, tris[hydroxymethyl]aminomethane, succinate, and polyethylene glycol
[PEG]).
• Genetic confirmation of ACH homozygous genotype.
• Premature birth with gestational age < 32 weeks.
• Premature birth with gestational age 32 to 37 weeks, unless time from birth is > 6
months at the time of screening and the child is in good nutritional status, defined
as gain in body weight expected for age and diagnosis of ACH, as determined by the
Investigator and confirmed with the Medical Monitor.
• Anticipated, as assessed by Investigator and confirmed with Medical Monitor, to
undergo surgical intervention during trial participation, including cervicomedullary
decompression. Evaluation of immediate risk of requiring cervicomedullary
decompression surgery will rely on the following assessments:
• Physical examination (e.g., neurologic findings of clonus, opisthotonus,
exaggerated reflexes, dilated facial veins)
• Evidence of uncontrolled sleep apnea as confirmed by local standard of care
assessment (e.g. polysomnography or simple sleep test) performed within 6 months
prior to screening.
• MRI performed at screening indicating presence of severe cervicomedullary
compression (CMC) or spinal cord damage. Presence of abnormal MRI T2 signal
intensity at and immediately above and below the cervicomedullary junction should
be considered high risk for requiring surgery and the participant is not eligible
for trial participation.
Common surgeries, such as insertion of grommets, adenoidectomy, tonsillectomy, or
myringotomy tube placement are permitted during trial participation.
• Have a growth disorder or medical condition, other than ACH, resulting in short
stature or abnormal growth as determined by the Investigator and confirmed with the
Medical Monitor.
• Have received any dose of prescription medications and/or investigational medicinal
product or device intended to affect stature, growth, or body proportionality
(including human growth hormone or vosoritide) at any time.
• Requires or anticipated to require chronic (> 4 weeks) or repeated treatment (more
than twice/year) with oral corticosteroids, or high-dose inhaled corticosteroids
during trial participation.
• History or presence of injury or disease of the growth plate(s), other than ACH,
affecting growth potential of long bones, including Salter-Harris fracture and recent
bone-related surgery, as determined by Investigator and confirmed with the Medical
Monitor.
• Have a clinically significant finding indicating abnormal cardiac function, including
but not limited to:
• Repaired or unrepaired coarctation.
• Moderate or greater complexity congenital heart disease including tetralogy of
Fallot, atrioventricular septal defects, truncus arteriosus, total anomalous
pulmonary venous return, double outlet right ventricle, or single ventricle heart
disease.
• QTcF ≥ 450 msec on screening 12-lead ECG.
• History or presence of a condition impacting hemodynamic stability (such as autonomic
dysfunction and orthostatic intolerance).
• History or presence of the following:
• Chronic anemia.
• Chronic renal insufficiency.
• Chronic or recurrent illness that can affect hydration or volume status,
including conditions associated with decreased nutritional intake or increased
volume loss.
• History or presence of malignant disease.
• Any disease or condition that, in the opinion of the Investigator, may make the
participant unlikely to fully complete the trial, not adhering to trial procedures,
may confound interpretation of trial results, or may present undue risk from receiving
trial treatment. This could include family situations, comorbid conditions, or
medications that might impact safety or be considered confounding.
A Study of Nemtabrutinib (MK-1026) Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in First Line (1L) Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) (MK-1026-011/BELLWAVE-011)
The goal of this study is to evaluate nemtabrutinib compared with investigator's choice of
ibrutinib or acalabrutinib in participants with chronic lymphocytic leukemia (CLL)/small
lymphocytic lymphoma (SLL) who have not received any prior therapy. The primary hypotheses
are that (1) nemtabrutinib is non-inferior to ibrutinib or acalabrutinib with respect to
objective response rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia
(iwCLL) Criteria 2018 by blinded independent central review (BICR) and (2) nemtabrutinib is
superior to ibrutinib or acalabrutinib with respect to progression free survival (PFS) per
iwCLL Criteria 2018 by BICR.
Christopher Fletcher, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT06136559
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Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
• Confirmed diagnosis of CLL/SLL and active disease clearly documented to have a need to
initiate therapy.
• Has at least 1 marker of disease burden.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7
days before randomization.
• Has the ability to swallow and retain oral medication.
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they
have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have
undetectable HBV deoxyribonucleic acid (DNA) viral load before randomization.
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV
ribonucleic acid (RNA) viral load is undetectable at screening.
• Participants with human immunodeficiency virus (HIV) who meet ALL eligibility
criteria.
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
• Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
• Has gastrointestinal (GI) dysfunction that may affect drug absorption.
• Has diagnosis of Richter Transformation or active central nervous system (CNS)
involvement by CLL/SLL.
• Has had acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in
the past 12 months before screening.
• Has clinically significant cardiovascular disease.
• Has hypersensitivity to nemtabrutinib or contraindication to ibrutinib or
acalabrutinib, or any of the excipients.
• Has history of severe bleeding disorder.
• Has history of second malignancy, unless potentially curative treatment has been
completed with no evidence of malignancy for 2 years.
• Has received any systemic anticancer therapy for CLL/SLL.
• Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow
therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A
strong inhibitors.
• Received prior radiotherapy within 2 weeks of start of study intervention, or
radiation-related toxicities, requiring corticosteroids.
• Received a live or live-attenuated vaccine within 30 days before the first dose of
study intervention. Administration of killed vaccines are allowed.
• Has received an investigational agent or has used an investigational device within 4
weeks before study intervention administration.
• Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study medication.
• Has active autoimmune disease that has required systemic treatment in the past 2
years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is
allowed.
• Has active infection requiring systemic therapy.
• Participants who have not adequately recovered from major surgery or have ongoing
surgical complications.
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Non-Hodgkin's Lymphoma, Lymphoma
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