Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
Conditions
Brief summary
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.
Detailed description
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 50 mg 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. THE MATCH SCREENING TRIAL: Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.
Interventions
PROCEDUREBiopsy Procedure
Undergo biopsy
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREComputed Tomography
Undergo CT scan
PROCEDUREEchocardiography Test
Undergo ECHO
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
PROCEDURERadionuclide Imaging
Undergo nuclear study
DRUGSunitinib
Given PO
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the 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. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point. |
| 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 | PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the 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. Please refer to the protocol for detailed definitions of disease progression. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLilian T Gien
ECOG-ACRIN Cancer Research Group
Participant flow
Recruitment details
Subprotocol V was activated on August 12, 2015. A total of 10 patients were enrolled between November 1, 2016 and May 21, 2020. Four patients were enrolled on the basis of the results from the NCI-MATCH assay and 6 on the basis of the outside assay results.
Pre-assignment details
Eligible patients for arm-V 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 in the protocol. The mutation status was determined by an NCI-MATCH approved laboratory for 6 patients in this arm, these cases had to be confirmed to be used in primary analysis.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Treatment (Sunitinib) |
|---|---|
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 10 |
| other Total, other adverse events | 6 / 9 |
| serious Total, serious adverse events | 5 / 9 |
Outcome results
Primary
Objective Response Rate (ORR)
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)
Time frame: 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
Population: Patients who were eligible, started protocol therapy, and had mutation status confirmed at the analysis time were the analyzable patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Sunitinib) | Objective Response Rate (ORR) | 22.2 percentage of participants |
Secondary
6-month Progression Free Survival (PFS)
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the 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. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
Time frame: 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
Population: Patients who were eligible, started protocol therapy, and had mutation status confirmed at the analysis time were the analyzable patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Sunitinib) | 6-month Progression Free Survival (PFS) | 33.3 percentage of participants |
Secondary
Progression Free Survival
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the 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. Please refer to the protocol for detailed definitions of disease progression.
Time frame: 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
Population: Patients who were eligible, started protocol therapy, and had mutation status confirmed at the analysis time were the analyzable patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Sunitinib) | Progression Free Survival | 4.2 months |