Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
Conditions
Brief summary
This phase II MATCH treatment trial identifies the effects of afatinib in patients whose cancer has genetic changes called HER2 mutations. Afatinib may stop the growth of cancer cells by blocking the HER2 receptor, a protein that may be needed for cell growth. Researchers hope to learn if afatinib will shrink this type of cancer or stop its growth.
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 dimaleate (afatinib) orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.
Interventions
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 prior to registration to treatment subprotocol * Patient's tumor must have activating HER2 mutation, as determined via the MATCH Master Protocol * Additionally, any in-frame insertions in exon 20 will be considered an activating mutation * 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 echocardiogram (ECHO) or a nuclear study (multiple-gated acquisition \[MUGA\] 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 have =\< grade 1 diarrhea at baseline * 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 * This should be strictly followed and will override the MATCH Master Protocol requirements
Exclusion criteria
* Patients must not have known hypersensitivity to afatinib or compounds of similar chemical or biologic composition * Patients with a history of interstitial lung disease will be excluded * Patients must not have had prior treatment with any of the following tyrosine kinase inhibitors (TKIs), which have known activity against HER2 kinase: * Neratinib * AC-480 (BMS-599626) * AST 1306 * Canertinib (CI 1033) * CUDC-101 * Lapatinib * TAK285 * Afatinib * AEE 788 * AZD8931 * CP-724714 * Dacomitinib * Pelitinib * Patients with non-small cell lung cancer will be excluded
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 | Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response 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 the detailed definitions of response criteria. The 90% two-sided binomial exact confidence interval was calculated for ORR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6-month Progression-free Survival (PFS) Rate | 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 (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 | 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
Participant flow
Recruitment details
Subprotocol B was activated on August 12, 2015. Fifty-nine patients were assigned to Subprotocol B after screening, all from screening cohort. Of the 59 patients, 40 patients were enrolled in arm B between August 2015 and June 2017.
Pre-assignment details
To be assigned to a specific MATCH subprotocol, patients needed to submit a tumor biopsy for molecular characterization and those with molecular variants addressed by treatments included in the trial entered corresponding MATCH subprotocol. For the subprotocol B, patients had to have a qualifying ERBB2 actionable mutation.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Afatinib Dimaleate) Patients receive afatinib dimaleate 40mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Afatinib Dimaleate: Given PO | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Alternative Therapy | 1 |
| Overall Study | Death | 3 |
| Overall Study | Disease Progression | 27 |
| Overall Study | Increased Tumor Burden | 1 |
| Overall Study | Ineligible | 1 |
| Overall Study | Never Started Treatment | 2 |
| Overall Study | Symptomatic Detrioration | 1 |
Baseline characteristics
| Characteristic | Treatment (Afatinib Dimaleate) |
|---|---|
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 2 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 37 / 40 |
| other Total, other adverse events | 31 / 37 |
| serious Total, serious adverse events | 18 / 37 |
Outcome results
Primary
Objective Response Rate (ORR)
Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response 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 the detailed definitions of response criteria. The 90% two-sided binomial exact confidence interval was 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: Patients who were eligible and received protocol treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Afatinib Dimaleate) | Objective Response Rate (ORR) | 2.7 percentage of participants |
Secondary
6-month Progression-free Survival (PFS) Rate
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: Patients who were eligible and received protocol treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Afatinib Dimaleate) | 6-month Progression-free Survival (PFS) Rate | 12.0 percentage of participants |
Secondary
Progression Free Survival (PFS)
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: Patients who were eligible and received protocol treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Afatinib Dimaleate) | Progression Free Survival (PFS) | 1.7 months |