Testing Afatinib as a Potential Targeted Treatment in Cancers With HER2 Genetic Changes (MATCH-Subprotocol B)

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Active, not recruiting

CT.gov ID

NCT04439136

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Lymphoma Advanced Malignant Solid Neoplasm Hematopoietic and Lymphoid Cell Neoplasm Refractory Lymphoma Refractory Malignant Solid Neoplasm Refractory Plasma Cell Myeloma	Drug: Afatinib Dimaleate	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

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:

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.
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.
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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

MATCH Treatment Subprotocol B: Phase II Study of Afatinib in Patients With Tumors With HER2 Activating Mutations

Actual Study Start Date :

Aug 12, 2015

Anticipated Primary Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (afatinib dimaleate) Patients receive afatinib dimaleate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Afatinib Dimaleate Given PO Other Names: (2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate) BIBW 2992MA2 BIBW2992 MA2 Gilotrif

Arm

Intervention/Treatment

Experimental: Treatment (afatinib dimaleate)

Patients receive afatinib dimaleate PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Afatinib Dimaleate

Given PO

Other Names:

(2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate)

BIBW 2992MA2

BIBW2992 MA2

Gilotrif

Outcome Measures

Primary Outcome Measures

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 eligible and treated patients. Objective response rate 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. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.

Secondary Outcome Measures

Overall survival (OS) [Assessed every 3 months for =< 2 years and every 6 months for year 3]
OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.
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 is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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