Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
Conditions
Keywords
Crizotinib, MET, Exon 14 Deletion, NCI-MATCH
Brief summary
This phase II MATCH treatment trial tests how well crizotinib works to treat patients with cancers with MET exon 14 deletion genetic changes. Crizotinib is in a group of medications called tyrosine kinase inhibitors. It works by blocking enzymes that cancer cells need to grow and spread. It may also prevent the growth of new blood vessels that tumors need to grow.
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 crizotinib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy on study and undergo radiologic evaluation and blood sample collection throughout the study. After completion of study treatment, patients followed up every 3 months for 2 years then every 6 months for year 3. THE MATCH SCREENING TRIAL: Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.
Interventions
PROCEDUREBiopsy Procedure
Undergo tumor biopsy
PROCEDUREBiospecimen Collection
Undergo blood sample collection
DRUGCrizotinib
Given PO
PROCEDURERadiologic Examination
Undergo radiologic evaluation
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 * Patient must fulfill all eligibility criteria outlined in Section 3.1 of MATCH Master protocol (excluding Section 3.1.6) at the time of registration to treatment step (Step 1, 3, 5, 7) * Patient must have MET exon 14 skipping as defined via the MATCH Master Protocol and described or other mutations that disrupt exon 14 that are approved as a dynamic aMOI * Patients must have an electrocardigram (ECG) within 8 weeks prior to treatment assignment and must not have clinically important abnormalities in rhythm, conduction or morphology of resting ECG, including complete left bundle branch block, third degree heart block * Patients must not have known hypersensitivity to crizotinib or compounds of similar chemical or biologic composition * Patient must not have had any of the following prior therapies: AMG 337, BMS 777607, cabozantinib (XL184), crizotinib (PF02341066), EMD1214063, foretinib (GSK1363089) (XL880), golvatinib (E7050), IncB28060 (INC280), JNJ 8877605, MGCD265, MK2461, MSC2156119J, PF 04217903, SGX523, tivantinib (ARQ197) or any other novel MET TKI with any MET inhibitory activity half-maximal inhibitory concentration (IC50) \< 1 uM. Prior anti-HGF or anti-MET antibodies are acceptable * Patients must not have a history of extensive disseminated/bilateral or known presence of grade 3 or 4 interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not history of prior radiation pneumonitis * Patients must not have had myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack within 3 months prior to start of study treatment. Clinically significant gastrointestinal (GI) abnormalities that may alter absorption (e.g., malabsorption syndrome, major resection of stomach or small bowel) * Patients using drugs or foods that are known strong CYP3A4 inhibitors or inducers will be excluded. Patients must not require concurrent use of CYP3A substrates with narrow therapeutic indices * Patients must not have had major surgery or tumor embolization within 4 weeks and minor surgery within 2 weeks prior to the initiation of the study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6-month Progression Free Survival (PFS) | Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined | 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 | Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles 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_INVESTIGATORDavid S Hong
ECOG-ACRIN Cancer Research Group
Participant flow
Recruitment details
Subprotocol C2 was activated on May 31, 2016. Twenty patients were enrolled on EAY131-C2 between July 20, 2016, and March 16, 2020. Sixteen patients were enrolled on the basis of the results from the NCI-MATCH assay and 4 on the basis of the outside assay results.
Pre-assignment details
For subprotocol C2, patients were required to have MET Exon 14 deletion by the Oncomine® Assay RNA-sequencing approach, and confirmation was performed retrospectively at the DNA level using Anchored Multiplex PCR, utilizing a custom targeted DNA sequencing panel and analysis pipeline that permitted analysis of the MET exon 14 coding region and surrounding intronic sequences.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 68 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 20 / 20 |
| other Total, other adverse events | 16 / 18 |
| serious Total, serious adverse events | 13 / 18 |
Outcome results
None listed