- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03425292
A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer
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.
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Santa Monica, California, United States, 90404
- Saint John's Cancer Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Participant has the ability to understand and the willingness to provide a signed and dated informed consent form.
- Participant has the willingness to comply with all study procedures and availability for the duration of the study.
- Participant is being evaluated for a potential, or known, diagnosis of high grade glioma.
- Participant is a candidate for brain surgery or has undergone prior surgery and has not received any additional treatment for high grade glioma.
- Participant is male or female, ≥ 18 years of age.
- Participant has a Karnofsky Performance Status (KPS) ≥ 60%:
Exclusion Criteria:
- Participant has received prior anti-cancer treatment for high grade glioma.
- Participant has a diagnosis of immunodeficiency or active autoimmune disease.
- 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.
- 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®).
- 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).
- Participant is a female of childbearing potential who is pregnant or nursing.
- Participant has a history of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months.
- Participant has a history of intestinal perforations, fistula, hemorrhages, and/or hemoptysis ≤ 6 months prior to first study treatment.
- Participant has active gastrointestinal bleeding.
- Participant has uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 1 SOC (closed to enrollment)
Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide
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concomitant and 5-day adjuvant temozolomide
Other Names:
standard radiation therapy for newly diagnosed glioblastoma
|
Experimental: 2 Nivo
Nivolumab
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nivolumab 300 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks
Other Names:
|
Experimental: 3 Nivo-Ipi (closed to enrollment)
Nivolumab plus Ipilimumab
|
nivolumab 240 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks
Other Names:
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
Other Names:
|
Experimental: 4 Nivo-Ipi-CCNU-TMZ
Nivolumab plus Ipilimumab plus Lomustine (CCNU) plus 5-day Temozolomide
|
nivolumab 240 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks
Other Names:
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
Other Names:
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)
Other Names:
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)
Other Names:
100 mg/m^2 oral, on Day 1 of each 6 week course
Other Names:
|
Experimental: 5 Nivo-Ipi-TMZ
Nivolumab plus Ipilimumab plus 5-day Temozolomide
|
nivolumab 240 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks
Other Names:
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
Other Names:
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)
Other Names:
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)
Other Names:
|
Experimental: 6 Nivo-Ipi-Bev-TMZ
Nivolumab plus Ipilimumab plus Bevacizumab plus 5-day Temozolomide
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nivolumab 240 mg IV every 2 weeks for the first 28-day cycle, then option to modify to 480 mg IV every 4 weeks
Other Names:
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
Other Names:
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)
Other Names:
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)
Other Names:
bevacizumab 5 mg/kg IV every 2 weeks (up to 10 mg/kg at treating physician's discretion)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of dose limiting toxicities
Time Frame: first 28 days of treatment
|
treatment-related adverse events that impact administration of treatment
|
first 28 days of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment-related adverse events
Time Frame: approximately 7 months
|
Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03.
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approximately 7 months
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Tumor response rates
Time Frame: up to 5 years
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Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria.
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up to 5 years
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Progression free survival (PFS)
Time Frame: up to 5 years
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The duration of time from start of treatment until objective tumor response.
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up to 5 years
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Overall survival (OS)
Time Frame: up to 5 years
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The duration of time from start of treatment to death.
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up to 5 years
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Levels of immunotherapeutic agents in specimens
Time Frame: approximately 4 months
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Immunotherapeutic drug levels in specimens.
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approximately 4 months
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Change in clinical molecular profile of tumor tissue after treatment
Time Frame: approximately 6 months to 1 year
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Comparison of tumor tissue molecular profile generated from before and after study treatment.
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approximately 6 months to 1 year
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Santosh Kesari, MD, PhD, Saint John's Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms
- Neoplasms by Site
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Brain Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Immune Checkpoint Inhibitors
- Temozolomide
- Nivolumab
- Bevacizumab
- Ipilimumab
- Lomustine
Other Study ID Numbers
- JWCI-17-0801
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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