Brigatinib and Bevacizumab for the Treatment of ALK-Rearranged Locally Advanced, Metastatic, or Recurrent NSCLC

Stage IV Lung Cancer AJCC v8 Clinical Trial

Official title: Phase Ib Study of Brigatinib Plus Bevacizumab in Patients With ALK-Rearranged Non-Small Cell Lung Cancer (NSCLC) Who Have Previously Progressed on Prior ALK-Directed Therapy

Status Active, not recruiting

Clinical Trial Summary

This phase Ib trial studies the side effects and best dose of brigatinib and how well it works with bevacizumab in treating patients with ALK-rearranged non-small cell lung cancer that has spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic) or has come back (recurrent). Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known if brigatinib and bevacizumab will work better in treating patients with ALK-rearranged non-small cell lung cancer.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine toxicity and tolerability, and the maximum tolerated dose (MTD) of brigatinib and bevacizumab in patients with ALK rearranged non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To describe the dose-limiting toxicities of brigatinib in combination with bevacizumab.

II. To estimate overall response rate (ORR) to treatment with brigatinib and bevacizumab.

III. To estimate the duration of response as defined by the time of first documented clinical benefit to the time of progression.

IV. To estimate patient survival by measuring progression free survival (PFS) as defined by the time from treatment initiation to documented disease progression or death from any cause. Overall survival (OS) as defined by the time from treatment initiation until death due to any cause.

EXPLORATORY OBJECTIVES:

I. To identify predictive biomarkers using genetics and tumor immunology-based assessment platforms.

Ia. Analysis with next-generation sequencing (NGS) to identify predictive biomarkers for response using tissue and cerebral spinal fluid (CSF) (optional for patients with brain metastases).

Ib. Tumor tissue will be obtained at baseline, and cell free deoxyribonucleic acid (DNA) (cfDNA)/cell tumor DNA (ctDNA) obtained at baseline and the time of progression or study completion will be evaluated for genomic alterations and biomarkers.

II. Evaluation of central nervous system (CNS) penetration through cerebral spinal fluid (CSF) obtained by lumbar puncture on cycle 2 day 1 (C2D1) (with time matched pharmacokinetic [PK] blood draw), and at progression or study completion for consenting patients (optional).

OUTLINE: This is a dose-escalation study of brigatinib.

Patients receive brigatinib orally (PO) once daily (QD) on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Patients also receive bevacizumab intravenously (IV) on day 8 of cycle 1 and day 1 of subsequent cycles. Starting cycle 2, cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, 3, 6, 9, and 12 months, then every 6 months for up to 3 years. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Locally Advanced Lung Non-Small Cell Carcinoma
• Lung Neoplasms
• Metastatic Lung Non-Small Cell Carcinoma
• Recurrent Lung Non-Small Cell Carcinoma
• Stage III Lung Cancer AJCC v8
• Stage IIIA Lung Cancer AJCC v8
• Stage IIIB Lung Cancer AJCC v8
• Stage IIIC Lung Cancer AJCC v8
• Stage IV Lung Cancer AJCC v8
• Stage IVA Lung Cancer AJCC v8
• Stage IVB Lung Cancer AJCC v8

• NCT number: NCT04227028
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 9, 2020
• Completion date: November 1, 2024