NCT03425292

A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 49 (actual)
• Sponsor: Saint John's Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to test the safety and tolerability of the research study drugs nivolumab, ipilimumab, lomustine, bevacizumab, and temozolomide when used following surgery and before standard therapy with radiation and temozolomide in patients with newly diagnosed high grade glioma. Additional aims of the study are to: * Find out side effects (good and bad) of study drug combinations. * Evaluate any preliminary evidence of anticancer activity of study drug combinations . * Evaluate tumor characteristics by collecting brain tumor tissue samples. * Measure the amount of nivolumab and ipilimumab in biospecimens. * Look at biomarkers in biospecimens.

Detailed description

Patients having a clinically planned surgical procedure (biopsy or cytoreduction) for a suspected diagnosis of high grade glioma will be approached for participation in this study. Tumor tissue obtained from surgery will be used for histological diagnosis and clinical molecular profiling, and excess tumor tissue will be collected for potential correlative studies. A small sample of blood and CSF for research will also be collected. Once a diagnosis of high grade glioma is confirmed, the patient will be allocated to one of the study arms. Treatment will be started approximately 7-42 days following surgery once the patient has recovered from surgery. Routine clinical evaluations will be performed prior to treatment initiation and throughout treatment as clinically indicated. Radiographic brain imaging will be performed approximately 21-42 after treatment initiation and then routinely for medical management. Tumor response will be assessed according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) Working Group criteria. Treatment may continue until the patient experiences unacceptable toxicity or clear disease progression. The determination of whether to stop treatment due to disease progression will be based on the investigator's evaluation of the patient's clinical and radiographic condition, taking into consideration the interpretation of localized inflammatory responses that can mimic radiographic features of tumor progress. Patients discontinuing treatment will have further medical management as directed by their treating physician. As part of follow-up, if the patient undergoes a surgery, results of clinical molecular profiling will be collected, and excess resected tumor tissue will be collected if available along with blood and CSF for correlative studies. A record of any additional anti-cancer treatments and survival status will be made every three to six months.

Conditions

• Newly Diagnosed High Grade Glioma

Interventions

Type	Name	Description
DRUG	Temozolomide	concomitant and 5-day adjuvant temozolomide
RADIATION	conformal brain radiation therapy	standard radiation therapy for newly diagnosed glioblastoma
DRUG	Nivolumab	nivolumab 240 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks
DRUG	Ipilimumab	ipilimumab 1 mg/kg IV every 6 weeks (or every 8 weeks when nivolumab is administered every 4 weeks) for a maximum of 4 doses
DRUG	Bevacizumab	bevacizumab 5 mg/kg IV every 2 weeks (up to 10 mg/kg at treating physician's discretion)
DRUG	5-day Temozolomide	150 mg/m\^2 oral, once daily on Days 1-5 of each 28-day cycle (stepwise titration every cycle up to 200 mg/m\^2 permitted)
DRUG	5-day Temozolomide	100 mg/m\^2 oral, once daily on Days 2-6 of each 6 week course (stepwise titration every cycle up to 200 mg/m\^2 permitted)
DRUG	Lomustine	100 mg/m\^2 oral, on Day 1 of each 6 week course
DRUG	Nivolumab monotherapy	nivolumab 300 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks

Timeline

• Start date: 2018-03-01
• Primary completion: 2022-09-12
• Completion: 2023-10-27
• First posted: 2018-02-07
• Last updated: 2023-11-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study