Nivolumab for Recurrent or Progressive IDH Mutant Gliomas
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03557359|
Recruitment Status : Recruiting
First Posted : June 15, 2018
Last Update Posted : October 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Gliomas||Drug: Nivolumab||Phase 2|
Gliomas are the most common malignant primary brain tumor in adults. Their clinical presentation is heterogeneous and prognosis is dependent on both the grade of the tumor and the molecular subtype. Somatic mutations in Isocitrate dehydrogenase 1 (IDH1) or, less commonly, Isocitrate dehydrogenase 2 (IDH2) genes have emerged as an important prognostic factor in gliomas and are associated with longer survival.
Regardless of initial grade, recurrence and transformation into higher grade tumors is almost universal. There is high unmet medical need in treating recurrent gliomas as there is currently no established standard of care therapy. Recent trials of IDH inhibitors in IDH mutant gliomas and programmed cell death protein 1 (PD-1) and PD-L1 inhibitors in recurrent gliomas have been disappointing. Multiple studies in other cancers have demonstrated that hypermutated tumors are associated with response to immunotherapeutic agents, including anti-CTLA4 agents in melanoma, anti-PD1 therapy in bladder cancer, and anti-programmed-cell-death protein 1 (anti-PD1) therapy in lung, and colorectal cancer.
There is evidence to suggest that gliomas with somatic IDH mutations are more prone to develop hypermutation after exposure to alkylating agents than IDH wildtype tumors, providing strong scientific rationale for establishing nivolumab as a treatment option in this subgroup of patients.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||37 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II, Open Label, Single Arm Study of Nivolumab for Recurrent or Progressive IDH Mutant Gliomas With Prior Exposure to Alkylating Agents|
|Actual Study Start Date :||June 12, 2018|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||June 2021|
Nivolumab 240 mg will be given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg will be given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab will be administered as a 30-minute infusion. A finite treatment duration with immune therapies in this participant population remains an area of ongoing research; therefore the treatment duration chosen was 2 years.
Nivolumab (Opdivo®) is a human monoclonal antibody (HuMAb; immunoglobulin G4 (IgG4)- S228P) that targets the PD-1 cluster of differentiation 279 (CD279) cell surface membrane receptor.
Other Name: Opdivo®
- Overall Response Rate [ Time Frame: Total treatment duration for 2 years or until PD, unacceptable toxicity, or withdrawal of consent. ]To evaluate the objective response rate (partial response (PR) and complete responses (CR)) to nivolumab of recurrent or progressive IDH mutant high-grade gliomas with prior exposure to alkylating agents.
- Duration of Response [ Time Frame: Until the first date that progressive disease is objectively documented or until study completion (36 months) ]The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
- Progression-Free Survival (PFS) [ Time Frame: Until death or study completion (36 months) ]
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Participants discontinuing study treatment will remain on study for documentation of progression and death.
- Overall Survival (OS) [ Time Frame: Until death or study completion (36 months) ]OS is defined as the time from the first dose of nivolumab to death due to any cause. All other participants will be censored at the last date known to be alive.
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): NCT03557359
|Contact: Fabio Iwamoto, MDemail@example.com|
|Contact: Natalie Busby, BSfirstname.lastname@example.org|
|United States, Florida|
|Miami Cancer Center||Not yet recruiting|
|Miami, Florida, United States, 33176|
|Contact: Yazmin Odia, MD 786-527-8952 YazminO@baptisthealth.net|
|Principal Investigator: Yazmin Odia, MD|
|United States, Massachusetts|
|Dana Farber Cancer Institute||Not yet recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Lakshmi Nayak, MD 617-632-6177 Lakshmi_Nayak@dfci.harvard.edu|
|Principal Investigator: Lakshmi Nayak, MD|
|Sub-Investigator: David Reardon, MD|
|Sub-Investigator: Patrick Wen, MD|
|Sub-Investigator: Eudocia Quant, MD|
|United States, New York|
|Columbia University Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Fabio Iwamoto, MD 212-342-0571 email@example.com|
|Contact: Natalie Busby, BS 212-305-8487 firstname.lastname@example.org|
|Principal Investigator: Fabio Iwamoto, MD|
|Sub-Investigator: Andrew Lassman, MD|
|Sub-Investigator: Teri Kreisl, MD|
|Sub-Investigator: Mary Welch, MD|
|Principal Investigator:||Fabio Iwamoto, MD||Columbia University|