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 afatinib works in treating patients with cancer that has certain genetic changes. Afatinib is in a class of medications called kinase inhibitors. It is used in patients whose cancer has a certain mutation (change) in the EGFR gene. It works by blocking the action of mutated EGFR 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 afatinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 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
DRUGAfatinib
Given PO
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
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) * Patient's tumor must have either of the below, or another aberration, as determined via the MATCH Master Protocol: * Activating mutations of EGFR (del 19, L858R) OR * Any malignancy harboring any of the following mutations: EGFR G719A, G719C, G719D, G719S EGFR L861Q, EGFR S768I * Tumors with an exon 20 insertion alone without the above mutations will be excluded, with the exception of exon 20 insertions approved as inclusion variants as part of the dynamic actionable mutation of interest (aMOI) process * 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 * NOTE: Pre-treatment LVEF determination in patients without known left ventricular dysfunction is NOT otherwise required * Patients must not have known hypersensitivity to afatinib or compounds of similar chemical or biologic composition * Patients must have =\< grade 1 renal function as defined below: * Creatinine =\< 1.5 x normal institutional limits OR * Measured creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal or as calculated by the Cockcroft-Gault equation * The above renal eligibility criteria should be strictly followed and will override the MATCH Master Protocol requirements * Patients must not have had prior treatment with an EGFR tyrosine kinase inhibitor (TKI) (e.g. afatinib, erlotinib, gefitinib, neratinib, dacomitinib, AZD9291, cabertinib, CO-1686) * Patients with non-small cell lung cancer and small cell lung cancer will be excluded * Patients with a history of interstitial lung disease will be excluded * Patients with glioblastoma multiforme (GBM) will be excluded * Patients must have =\< grade 1 diarrhea at baseline
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_INVESTIGATORScott N Gettinger
ECOG-ACRIN Cancer Research Group
Participant flow
Recruitment details
Subprotocol A was activated on August 12, 2015. Nineteen patients were enrolled between February 2018 and January 2020. All patients were enrolled though the outside laboratory and had their samples centrally confirmed.
Pre-assignment details
EGFR variants allowing entry into subprotocol A included classic activating deletion 19 and L858R EGFR mutations, EGFR G719A, G719C, G719D, G719S, L861Q, and S768I. The mutation status was determined by a CLIA-approved assay performed in an NCI-MATCH approved laboratory, these cases had to be confirmed to be used in primary analysis.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Afatinib) Patients receive afatinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 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 may also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study. | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | Treatment (Afatinib) |
|---|---|
| Age, Continuous | 58 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 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 | 15 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 19 |
| other Total, other adverse events | 15 / 17 |
| serious Total, serious adverse events | 2 / 17 |
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.
Time frame: 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
Population: Eligible, treated and mutation status confirmed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Afatinib) | Objective Response Rate (ORR) | 11.8 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: 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
Population: Eligible, treated and mutation status confirmed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Afatinib) | 6-month Progression Free Survival (PFS) | 15 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: 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
Population: Eligible, treated and mutation status confirmed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Afatinib) | Progression Free Survival | 1.7 months |