Clinical Trial 19327

Cancer Type: Neurologic Oncology
Study Type: Treatment
NCT#: NCT02681549

Phase: Phase II
Principal Investigator: Forsyth, Peter

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Overview

Study Title

A Phase 2 Trial of Pembrolizumab Plus Bevacizumab in Patients with Metastatic Melanoma or Non-small Cell Lung Cancer with Untreated Brain Metastases

Summary

The purpose of this study is to explore whether or not pembrolizumab combined with bevacizumab has beneficial effects and is safe for use in participants diagnosed with metastatic melanoma or non-small cell lung cancer (NSCLC) who also have untreated brain metastases. Investigators will also study the effects of this combination on tumors outside of the brain (when present) and on survival.

Objective

Primary Objectives/Endpoints: 1. To determine the brain metastasis response rate in patients with melanoma or NSCLC with untreated brain metastases, treated systemically with pembrolizumab plus bevacizumab. Secondary Objectives/Endpoints: 1. To determine the incidence of steroid use for control of cerebral edema during treatment with pembrolizumab plus bevacizumab in patients with metastatic melanoma or NSCLC to the brain compared to previous study of patients treated with pembrolizumab alone. 2. To determine the best overall response rate (ORR) in patients with brain metastases from melanoma or NSCLC treated with combination pembrolizumab plus bevacizumab. 3. To evaluate median progression free survival (PFS) and overall survival (OS) in patients with melanoma or NSCLC metastatic to the brain, treated with pembrolizumab plus bevacizumab. 4. To determine the safety of pembrolizumab in combination with bevacizumab in patients with untreated brain metastases from melanoma or NSCLC. Exploratory Objective: To study PD-L1 expression and other potential predictive biomarkers in CNS, tumors and blood, and correlate results with response to pembrolizumab plus bevacizumab.

Treatments

Therapies

Immunotherapy

Medications

Avastin (Bevacizumab); Bevacizumab (); Pembrolizumab (Keytruda)

Inclusion Criteria

Biopsy proven metastatic melanoma or non-squamous non-small cell lung cancer (NSCLC) with at least one untreated brain metastasis that is at least 5 mm AND twice the MRI slice thickness, but less than 20 mm, which is asymptomatic and not requiring immediate local therapy or steroids.

Patients who have had prior resection or biopsy of a central nervous system (CNS) metastasis will be required to provide a paraffin embedded specimen from tumor taken at the time of surgery, if available.

Participants will be required to undergo biopsy or submit archival tumor tissue from a systemic site of disease for correlative studies. When not feasible, this requirement can be waived after discussion with the principal investigators.

PD-L1 expression in tumor tissue from any site is required for patients with NSCLC. PDL1 expression will be analyzed by a Merck assay.

Adequate organ function.

Eastern Cooperative Oncology Group (ECOG) performance status less than 2.

Any number of previous treatments with the exception of previous inhibitors of PD-1 or PD-L1.

Life expectancy of at least 3 months.

Understanding and willingness to consent.

A history of radiotherapy for brain metastases is allowed, but any lesion present at the time of WBRT or included in the stereotactic radiotherapy field will NOT be considered evaluable unless documented to have progressed since treatment.

Additional criteria may apply

Exclusion Criteria

Symptomatic brain metastases at the time of initiation of systemic therapy.

Other systemic therapy within 14 days of initiation of study drug.

Use of corticosteroids to control CNS symptoms. Low-dose steroid use (≤10 mg of prednisone or equivalent) is allowed.

Presence of leptomeningeal disease.

Presence of active autoimmune disease. Autoimmune thyroid disease will be allowed if thyroid function is within normal range.