Description:
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.
Title
- Brief Title: A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer
- Official Title: A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer
Clinical Trial IDs
- ORG STUDY ID:
JWCI-17-0801
- NCT ID:
NCT03425292
Conditions
- Newly Diagnosed High Grade Glioma
Interventions
Drug | Synonyms | Arms |
---|
Temozolomide | temodar | 1 SOC (closed to enrollment) |
Nivolumab | opdivo | 2 Nivo |
Ipilimumab | yervoy | 3 Nivo-Ipi (closed to enrollment) |
Bevacizumab | avastin | 6 Nivo-Ipi-Bev-TMZ |
Metronomic Temozolomide | temodar | 5 Nivo-Ipi-TMZ |
5-day Temozolomide | temodar | 4 Nivo-Ipi-CCNU-TMZ |
Lomustine | CCNU | 4 Nivo-Ipi-CCNU-TMZ |
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
1 SOC (closed to enrollment) | Active Comparator | Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide | |
2 Nivo | Experimental | Nivolumab | |
3 Nivo-Ipi (closed to enrollment) | Experimental | Nivolumab plus Ipilimumab | |
4 Nivo-Ipi-CCNU-TMZ | Experimental | Nivolumab plus Ipilimumab plus Lomustine (CCNU) plus 5-day Temozolomide | - Nivolumab
- Ipilimumab
- 5-day Temozolomide
- Lomustine
|
5 Nivo-Ipi-TMZ | Experimental | Nivolumab plus Ipilimumab plus metronomic Temozolomide | - Nivolumab
- Ipilimumab
- Metronomic Temozolomide
|
6 Nivo-Ipi-Bev-TMZ | Experimental | Nivolumab plus Ipilimumab plus Bevacizumab plus metronomic Temozolomide | - Nivolumab
- Ipilimumab
- Bevacizumab
- Metronomic Temozolomide
|
Eligibility 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).
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Rate of dose limiting toxicities |
Time Frame: | first 28 days of treatment |
Safety Issue: | |
Description: | treatment-related adverse events that impact administration of treatment |
Secondary Outcome Measures
Measure: | Treatment-related adverse events |
Time Frame: | approximately 7 months |
Safety Issue: | |
Description: | Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.03. |
Measure: | Tumor response rates |
Time Frame: | up to 5 years |
Safety Issue: | |
Description: | Evidence of anti-tumor activity as measured according to immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria. |
Measure: | Progression free survival (PFS) |
Time Frame: | up to 5 years |
Safety Issue: | |
Description: | The duration of time from start of treatment until objective tumor response. |
Measure: | Overall survival (OS) |
Time Frame: | up to 5 years |
Safety Issue: | |
Description: | The duration of time from start of treatment to death. |
Measure: | Levels of immunotherapeutic agents in specimens |
Time Frame: | approximately 4 months |
Safety Issue: | |
Description: | Immunotherapeutic drug levels in specimens. |
Measure: | Change in clinical molecular profile of tumor tissue after treatment |
Time Frame: | approximately 6 months to 1 year |
Safety Issue: | |
Description: | Comparison of tumor tissue molecular profile generated from before and after study treatment. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | John Wayne Cancer Institute |
Trial Keywords
- immunotherapy
- nivolumab
- ipilimumab
- bevcizumab
- temozolomide
Last Updated
April 15, 2021