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Testing Sunitinib as Potentially Targeted Treatment in Cancers With cKIT Genetic Changes (MATCH - Subprotocol V)

Study Purpose

This phase II MATCH treatment trial tests how well sunitinib in treating patients with cancer that has certain genetic changes. Sunitinib is in a class of medications called kinase inhibitors. It is used in patients whose cancer has a certain mutation (change) in the cKIT gene. It works by blocking the action of mutated cKIT that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol.
  • - Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7) - Patients must have a somatic cKIT mutation in exon 9, 11, 13 or 14, excluding exon 17 or 18 mutations, activating PDGFRA or PDGFRB variants and fusions, or another aberration, as identified via the MATCH Master Protocol.
  • - Actionable mutations of interest (aMOIs)for information on the inclusion and exclusion mutations, along with the corresponding levels of evidence (LOE) - Total bilirubin must be within normal institutional limits.
  • - Creatinine must be within normal institutional limits.
OR Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
  • - Serum calcium must be =< 12.0 mg/dL.
  • - Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block) - Patients with known left ventricular dysfunction must have ECHO or a nuclear study (multigated acquisition scan [MUGA] or first pass) within 4 weeks prior to registration to treatment and must not have left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN).
If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible.
  • - The following groups of patients are eligible provided they have New York Heart Association class II cardiac function on baseline ECHO/nuclear study: - Patients with a history of class II heart failure who are asymptomatic on treatment.
  • - Patients with prior anthracycline exposure.
  • - Patients who have received central thoracic radiation that included the heart in the radiotherapy port NOTE: Pre-treatment LVEF determination in patients without known left ventricular dysfunction (or per Section 2.1.
5.1) is NOT otherwise required.
  • - Patients with any of the following conditions are excluded: - Serious or non-healing wound, ulcer, or bone fracture.
  • - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment.
  • - Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry.
  • - History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry.
  • - History of pulmonary embolism within the past 12 months.
  • - Patients must not have known hypersensitivity or excess toxicity from sunitinib or compounds of similar chemical composition or biologic effect.
This list includes, but is not limited to, patients with significant cardiac or hepatic toxicity from multikinase inhibitors with similar kinase inhibitory profiles (sorafenib, regorafenib, pazopanib)
  • - Questions regarding a significant intolerance to a prior therapy should be directed to the sub-protocol principal investigator (PI) - Patients must not have had prior therapy with sunitinib.
  • - Patients must not have planned ongoing administration of STRONG and MODERATE CYP3A4 inhibitors or inducers.
The reference list of cytochrome p450 (CYP) isozymes and classification of strong, moderate, and weak interactions is available through the FDA website.
  • - Strong CYP3A4 inhibitors are not permitted within 7 days before dosing and should be avoided throughout the study.
  • - Strong CYP3A4 inducers are not permitted within 12 days before dosing and should be avoided throughout the study.
  • - Patients must not have gastrointestinal stromal tumor (GIST), renal cell carcinoma, or pancreatic neuroendocrine tumor.
  • - Patients must not have a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 grade 3 hemorrhage within 4 weeks of starting study treatment.
  • - Patients must not have hypertension that cannot be controlled by medications (> 140/90 mmHg despite optimal medical therapy) - Patients must not have pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
  • - Participants may not have a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting sunitinib.
  • - Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Patients who require therapeutic doses of coumarin derivative anticoagulants such as warfarin are excluded, although doses up to 2 mg daily are permitted for prophylaxis of thrombosis NOTE: Low molecular weight heparin is permitted provided that the patient's prothrombin time (PT) international normalized ratio (INR) is < 1.5

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06390826
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

National Cancer Institute (NCI)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Lilian T Gien
Principal Investigator Affiliation ECOG-ACRIN Cancer Research Group
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

NIH
Overall Status Active, not recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
Additional Details

PRIMARY OBJECTIVE:

  • I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
  • I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.
  • II. To evaluate time until death or disease progression.
  • III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.
  • IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.
OUTLINE: Patients receive sunitinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo echocardiography (ECHO) or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

Arms & Interventions

Arms

Experimental: Treatment (sunitinib)

Patients receive sunitinib PO QD on days 1-28 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.

Interventions

Procedure: - Biopsy

Undergo biopsy

Procedure: - Biospecimen Collection

Undergo blood sample collection

Procedure: - Computed Tomography

Undergo CT scan

Procedure: - Echocardiography

Undergo ECHO

Procedure: - Magnetic Resonance Imaging

Undergo MRI

Procedure: - Radionuclide Imaging

Undergo nuclear study

Drug: - Sunitinib

Given PO

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

ECOG-ACRIN Cancer Research Group, Philadelphia, Pennsylvania

Status

Address

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103