A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer
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|ClinicalTrials.gov Identifier: NCT03425292|
Recruitment Status : Recruiting
First Posted : February 7, 2018
Last Update Posted : October 10, 2018
The purpose of this study is to test the safety and tolerability of nivolumab or nivolumab plus ipilimumab when used following surgery and before standard therapy with radiation and temozolomide in patients with newly diagnosed glioblastoma.
Additional aims of the study are to:
- Find out side effects (good and bad) of nivolumab and ipilimumab.
- Evaluate any preliminary evidence of anticancer activity of nivolumab and ipilimumab.
- 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 Glioblastoma||Drug: Temozolomide Radiation: conformal brain radiation therapy Drug: Nivolumab Drug: Ipilimumab||Phase 1|
Patients having a clinically planned surgical procedure (biopsy or cytoreduction) for a suspected diagnosis of glioblastoma 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 glioblastoma is confirmed, the patient will be randomized 1:1:1 to Treatment Arm 1 standard of care (radiation + chemotherapy), Treatment Arm 2 (nivolumab), or Treatment Arm 3 (nivolumab + ipilimumab). 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 be directed by their treating physician for the next step in their medical management - such as a clinically-indicated cytoreductive surgery, standard radiation chemotherapy if assigned to study arm 2 or 3, or a different treatment regimen. If another treatment is started, clinical evaluations and response assessments will continue as clinically-indicated; blood and CSF will be collected after the first month, then every three to six months.
|Study Type :||Interventional|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Longitudinal Assessment of Tumor Evolution in Patients With Brain Cancer|
|Actual Study Start Date :||March 1, 2018|
|Estimated Primary Completion Date :||February 1, 2019|
|Estimated Study Completion Date :||February 1, 2020|
Active Comparator: Standard radiation plus temozolomide
Standard conformal brain radiation therapy with concurrent and adjuvant temozolomide
concomitant and adjuvant temozolomide
Other Name: temodar
Radiation: conformal brain radiation therapy
standard radiation therapy for newly diagnosed glioblastoma
nivolumab 300 mg IV every 2 weeks
Other Name: opdivo
Experimental: Nivolumab plus ipilimumab
Nivolumab plus Ipilimumab
nivolumab 300 mg IV every 2 weeks
Other Name: opdivo
ipilimumab 1 mg/kg IV every 6 weeks
Other Name: yervoy
- 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 nivolumab and ipilimumab in specimens [ Time Frame: approximately 4 months ]Nivolumab and/or ipilimumab 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.
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
|Contact: Trial Teamfirstname.lastname@example.org|
|Contact: Jaya Gill, RNemail@example.com|
|United States, California|
|John Wayne Cancer Institute||Recruiting|
|Santa Monica, California, United States, 90404|
|Contact: Jaya Gill, RN 310-582-7437 firstname.lastname@example.org|
|Principal Investigator: Santosh Kesari, MD, PhD|
|Principal Investigator:||Santosh Kesari, MD, PhD||John Wayne Cancer Institute|