Testing Afatinib as Potentially Targeted Treatment in Cancers With EGFR Genetic Changes (MATCH - Subprotocol A)

Refractory Multiple Myeloma Clinical Trial

Official title:

MATCH Treatment Subprotocol A: Phase II Trial of Afatinib in Patients With Solid Tumors (Other Than Small Cell and Non-Small Cell Lung Cancer) or Lymphomas, That Have Activating Mutations of EGFR and Have Progressed After Standard Treatment

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06385483
• Other study ID #: NCI-2024-01125
• Secondary ID: NCI-2024-01125EA
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 11, 2015
• Est. completion date: December 6, 2024

Study information

• Verified date: May 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 35
• Est. completion date: December 6, 2024
• Est. primary completion date: December 6, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Lymphoma
• Advanced Malignant Solid Neoplasm
• Lymphoma
• Multiple Myeloma
• Neoplasms
• Refractory Lymphoma
• Refractory Malignant Solid Neoplasm
• Refractory Multiple Myeloma

Intervention

Drug:
• Afatinib
Given PO

Procedure:
• Biopsy
Undergo biopsy
• Biospecimen Collection
Undergo blood sample collection
• Computed Tomography
Undergo CT scan
• Echocardiography
Undergo ECHO
• Magnetic Resonance Imaging
Undergo MRI
• Radionuclide Imaging
Undergo nuclear study

Locations

Country	Name	City	State
United States	ECOG-ACRIN Cancer Research Group	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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. 90% two-sided confidence interval is calculated for ORR. For the purposes of this study, patients should be re-evaluated for response: 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)	Up to 3 years
Secondary	Overall survival (OS)	Will be evaluated specifically for each drug (or step). OS will be estimated using the Kaplan-Meier method.	From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years
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.	From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months
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.	From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years