A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03425292 |
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Recruitment Status :
Active, not recruiting
First Posted : February 7, 2018
Last Update Posted : February 21, 2023
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Newly Diagnosed High Grade Glioma | Drug: Temozolomide Radiation: conformal brain radiation therapy Drug: Nivolumab Drug: Ipilimumab Drug: Bevacizumab Drug: 5-day Temozolomide Drug: Lomustine Drug: Nivolumab monotherapy | Phase 1 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 90 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer |
| Actual Study Start Date : | March 1, 2018 |
| Actual Primary Completion Date : | September 12, 2022 |
| Estimated Study Completion Date : | March 1, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 1 SOC (closed to enrollment)
Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide
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Drug: Temozolomide
concomitant and 5-day adjuvant temozolomide
Other Name: temodar Radiation: conformal brain radiation therapy standard radiation therapy for newly diagnosed glioblastoma |
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Experimental: 2 Nivo
Nivolumab
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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
Other Name: opdivo |
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Experimental: 3 Nivo-Ipi (closed to enrollment)
Nivolumab plus Ipilimumab
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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
Other Name: opdivo 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
Other Name: yervoy |
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Experimental: 4 Nivo-Ipi-CCNU-TMZ
Nivolumab plus Ipilimumab plus Lomustine (CCNU) plus 5-day Temozolomide
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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
Other Name: opdivo 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
Other Name: yervoy 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)
Other Name: temodar Drug: Lomustine 100 mg/m^2 oral, on Day 1 of each 6 week course
Other Name: CCNU |
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Experimental: 5 Nivo-Ipi-TMZ
Nivolumab plus Ipilimumab plus 5-day Temozolomide
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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
Other Name: opdivo 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
Other Name: yervoy 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)
Other Name: temodar |
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Experimental: 6 Nivo-Ipi-Bev-TMZ
Nivolumab plus Ipilimumab plus Bevacizumab plus 5-day Temozolomide
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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
Other Name: opdivo 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
Other Name: yervoy Drug: Bevacizumab bevacizumab 5 mg/kg IV every 2 weeks (up to 10 mg/kg at treating physician's discretion)
Other Name: avastin 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)
Other Name: temodar |
- Rate of dose limiting toxicities [ Time Frame: first 28 days of treatment ]treatment-related adverse events that impact administration of treatment
- 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.
- Tumor response rates [ Time Frame: up to 5 years ]Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria.
- Progression free survival (PFS) [ Time Frame: up to 5 years ]The duration of time from start of treatment until objective tumor response.
- Overall survival (OS) [ Time Frame: up to 5 years ]The duration of time from start of treatment to death.
- Levels of immunotherapeutic agents in specimens [ Time Frame: approximately 4 months ]Immunotherapeutic drug levels in specimens.
- Change in clinical molecular profile of tumor tissue after treatment [ Time Frame: approximately 6 months to 1 year ]Comparison of tumor tissue molecular profile generated from before and after study treatment.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03425292
| United States, California | |
| Saint John's Cancer Institute | |
| Santa Monica, California, United States, 90404 | |
| Principal Investigator: | Santosh Kesari, MD, PhD | Saint John's Cancer Institute |
| Responsible Party: | Santosh Kesari, Professor, Neurosciences, Saint John's Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT03425292 |
| Other Study ID Numbers: |
JWCI-17-0801 |
| First Posted: | February 7, 2018 Key Record Dates |
| Last Update Posted: | February 21, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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immunotherapy nivolumab ipilimumab bevcizumab temozolomide |
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Brain Neoplasms Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Neoplasms Brain Diseases Central Nervous System Diseases Nervous System Diseases Bevacizumab Nivolumab Ipilimumab Temozolomide |
Lomustine Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Alkylating Alkylating Agents |