MATCH Treatment Subprotocol V: Phase II Study of Sunitinib in Patients With Tumors With cKIT Mutations (Excluding GIST, Renal Cell Carcinoma or Pancreatic Neuorendocrine Tumor)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
Treatment (sunitinib)
Patients receive sunitinib 50 mg 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.
干预措施: Echocardiography Test (Procedure)
Treatment (sunitinib)
Patients receive sunitinib 50 mg 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.
干预措施: Biopsy Procedure (Procedure)
Treatment (sunitinib)
Patients receive sunitinib 50 mg 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.
干预措施: Biospecimen Collection (Procedure)
Treatment (sunitinib)
Patients receive sunitinib 50 mg 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.
干预措施: Computed Tomography (Procedure)
Treatment (sunitinib)
Patients receive sunitinib 50 mg 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.
干预措施: Radionuclide Imaging (Procedure)
Treatment (sunitinib)
Patients receive sunitinib 50 mg 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.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (sunitinib)
Patients receive sunitinib 50 mg 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.
干预措施: Sunitinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Tumor assessments occurred at baseline, then every 3 months if patient is < 2 years from study entry, and every 6 months thereafter until disease progression, up to 3 years post registration
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.\* For treatments given in 21 day (3 week) cycles: every 3 cycles (9 weeks) for the first 33 cycles, and every 4 cycles thereafter (12 weeks) * For treatments given in 28 day (4 week) cycles: every 2 cycles (8 weeks) for the first 26 cycles, and every three cycles thereafter (12 weeks) * For treatments given in 42 day (6 week) cycles: every 2 cycles (12 weeks)
次要结局
- Progression Free Survival(Tumor assessments occurred at baseline, then every 3 months if patient is < 2 years from study entry, and every 6 months thereafter until disease progression, up to 3 years post registration)
- 6-month Progression Free Survival (PFS)(Tumor assessments occurred at baseline, then every 3 months if patient is < 2 years from study entry, and every 6 months thereafter until disease progression, up to 3 years post registration)