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A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Participant has the ability to understand and the willingness to provide a signed and dated informed consent form. 2. Participant has the willingness to comply with all study procedures and availability for the duration of the study. 3. Participant is being evaluated for a potential, or known, diagnosis of high grade glioma. 4. Participant is a candidate for brain surgery or has undergone prior surgery and has not received any additional treatment for high grade glioma. 5. Participant is male or female, ≥ 18 years of age. 6. Participant has a Karnofsky Performance Status (KPS) ≥ 60%:

Exclusion Criteria:

1. Participant has received prior anti-cancer treatment for high grade glioma. 2. Participant has a diagnosis of immunodeficiency or active autoimmune disease. 3. Participant is receiving chronic systemic steroid therapy in dosing exceeding 8 mg daily of dexamethasone equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Note: This is assessed after surgery, prior to starting drug treatment. 4. Participant has received a live vaccine within 28 days prior to the first dose of study agent. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), typhoid vaccine, and intranasal influenza vaccines (e.g., FluMist®). 5. Participant has a severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study intervention (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements). 6. Participant is a female of childbearing potential who is pregnant or nursing. 7. Participant has a history of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months. 8. Participant has a history of intestinal perforations, fistula, hemorrhages, and/or hemoptysis ≤ 6 months prior to first study treatment. 9. Participant has active gastrointestinal bleeding. 10. Participant has uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg).

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03425292
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

John Wayne Cancer Institute
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Santosh Kesari, MD, PhD
Principal Investigator Affiliation John Wayne Cancer Institute
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Newly Diagnosed High Grade Glioma
Additional Details

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.

Arms & Interventions

Arms

Active Comparator: 1 SOC (closed to enrollment)

Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide

Experimental: 2 Nivo

Nivolumab

Experimental: 3 Nivo-Ipi (closed to enrollment)

Nivolumab plus Ipilimumab

Experimental: 4 Nivo-Ipi-CCNU-TMZ

Nivolumab plus Ipilimumab plus Lomustine (CCNU) plus 5-day Temozolomide

Experimental: 5 Nivo-Ipi-TMZ

Nivolumab plus Ipilimumab plus metronomic Temozolomide

Experimental: 6 Nivo-Ipi-Bev-TMZ

Nivolumab plus Ipilimumab plus Bevacizumab plus metronomic Temozolomide

Interventions

Drug: - Temozolomide

concomitant and 5-day adjuvant temozolomide

Radiation: - conformal brain radiation therapy

standard radiation therapy for newly diagnosed glioblastoma

Drug: - Nivolumab

nivolumab 300 mg IV every 2 weeks

Drug: - Ipilimumab

ipilimumab 1 mg/kg IV every 6 weeks

Drug: - Bevacizumab

bevacizumab 5 mg/kg IV every 2 weeks

Drug: - Metronomic Temozolomide

50 mg/m^2 oral, once daily

Drug: - 5-day Temozolomide

100 mg/m^2 oral, once daily on Days 2-6 of each 6 week course

Drug: - Lomustine

100 mg/m^2 oral, on Day 1 of each 6 week course

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

John Wayne Cancer Institute, Santa Monica, California

Status

Recruiting

Address

John Wayne Cancer Institute

Santa Monica, California, 90404

Site Contact

Trial Team

neuro.oncology@jwci.org

310-829-8265