NCT04434560

Neoadjuvant Immunotherapy in Brain Metastases

A Phase II Trial of Surgery and Stereotactic Radiosurgery With Neoadjuvant Nivolumab and Ipilimumab in Patients With Surgically-resectable, Solid Tumor Brain Metastases

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Sarah Sammons, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this phase 2 study is to assess the feasibility and efficacy of neoadjuvant immunotherapy in patients with previously untreated, surgically-resectable, solid tumor brain metastases. The primary objectives of this study are to 1) assess the feasibility of neoadjuvant ipilimumab and nivolumab treatment before surgery and stereotactic radiosurgery (SRS) in patients with solid tumor brain metastases as measured by the proportion of patients who have their surgery delayed or surgery never occurs, and 2) demonstrate that neoadjuvant immunotherapy will increase proliferation of circulating T-cells compared to baseline measurements. Exploratory objectives include describing patient progression free survival and overall survival, time to local and distant intracranial progression, and the rate of radiation necrosis. The rate of radionecrosis will also be explored, as immune expression profiles.

Detailed description

Forty patients planned for standard of care resection of at least one solid tumor brain metastasis will be enrolled onto the study after providing informed consent. Primary tumor histology types are restricted to those known to extracranially respond to immunotherapy, and will include, but not be limited to, squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC without known anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), and ROS mutation, renal cell carcinoma (RCC), melanoma, and triple negative breast cancer (TNBC) that is programmed death-ligand 1 positive (PD-L1 +). All participants will receive neoadjuvant immunotherapy and will receive a single infusion of nivolumab at a dose of 3 mg/kg and ipilimumab at a dose of 1 mg/kg 7 days (±3 days) prior to surgical resection of their metastases. Approximately three weeks after resection, patients in will then receive SRS per standard of care guidelines. Patients will be followed for 18 months after initiating study treatment. Up to 20 participants will be recruited and treated. Blood will be collected periodically during the study for correlative assessments.

Conditions

• Brain Metastases, Adult

Interventions

Type	Name	Description
DRUG	Nivolumab	Nivolumab will be given at the FDA-approved dose of 3 mg/kg.
DRUG	Ipilimumab	Ipilimumab will be given at the FDA-approved dose of 1 mg/kg.

Timeline

• Start date: 2020-11-04
• Primary completion: 2021-06-17
• Completion: 2021-06-17
• First posted: 2020-06-17
• Last updated: 2022-07-26
• Results posted: 2022-07-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study