A Phase I/II Trial of Combination Tumor Treating Fields, Nivolumab Plus/Minus Ipilimumab for Recurrent Glioblastoma
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab 240 mg IV
- Conditions
- Recurrent Glioblastoma
- Sponsor
- Baptist Health South Florida
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Objective Response Rate According to Modified iRANO Criteria
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab.
Detailed Description
Phase I/II trial in which participants with recurrent glioblastoma will receive a combination of tumor treating fields(portable device), nivolumab with or without ipilimumab. The NovoTTF200A (OptuneTM) device is worn continuously for a goal of 75% or more of the time, ranging from at least 18 hours daily uninterrupted or 22 hours daily with 2-3 days off monthly. Therapy is planned for approximately 24 months. Infusions with nivolumab will start within 1 week of study start. Ipilimumab will either start with the second nivolumab infusion or at after tumor progression. Nivolumab is infused intravenously at 240 mg once every 2 weeks with or without ipilimumab for a maximum of 24 months. Ipilimumab is dosed at 1 mg/kg once every 6 weeks for a maximum of 4 doses (24 weeks). Infusions will continue until maximum doses are completed or there is confirmed tumor progression, intolerable adverse effects or withdrawal of consent.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed World Health Organization Grade IV glioblastoma with supratentorial distribution.
- •Unequivocal evidence of progressive disease on contrast-enhanced brain CT or MRI as defined by Response Assessment in Neuro-Oncology (RANO) criteria, or documented recurrent glioblastoma on biopsy.
- •Measurable disease based on RANO criteria.
- •Prior therapies including radiation and temozolomide.
- •Any number of recurrences are allowed. Resection of recurrent glioblastoma is not considered a prior treatment.
- •From the projected start date of study treatment, the following periods must have elapsed: 4 weeks from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), or 4 weeks from any other antibodies or any other antineoplastic therapies.
- •Must be at least 12 weeks from radiotherapy or progression outside of the high-dose radiation target volume or unequivocal evidence of progressive tumor on biopsy.
- •All adverse events Grade \> 1 related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved, except for alopecia.
- •Karnofsky Performance Status (KPS) ≥ 60
- •Adequate organ and marrow function as defined below, all screening labs should be performed within 14 days of treatment initiation:
Exclusion Criteria
- •Infratentorial disease.
- •Bevacizumab within 2 months of enrollment. Prior use of ipilimumab or other CTLA-4 inhibitor or prior TTFields.
- •Tumors with known IDH1 (isocitrate dehydrogenase 1) or IDH2 mutations as determined by immunohistochemistry for the IDH1 R132H variant or by direct sequencing. IDH1/2-mutant gliomas have a prolonged overall survival rate compared to IDH1/2-wildtype gliomas, indicating distinct natural history.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or ipilimumab or their excipients.
- •Current or planned participation in a study of an investigational agent or using an investigational device.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
- •Active or life-threatening infection requiring intravenous or \>2 weeks of systemic therapy.
- •Prior stereotactic radiotherapy, convection enhanced delivery (CED) or brachytherapy requires a biopsy to confirm radiographic progression is consistent with progressive tumor and not treatment-related necrosis unless the recurrent lesion is outside of any prior high-dose radiation target volume or distant from the prior CED or brachytherapy site.
- •There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, so breastfeeding must be discontinued by enrollment on study.
- •Uncontrolled HIV or AIDS is not allowed. Patients with known history of HIV but with undetectable viral load on antiretroviral therapy are allowed.
Arms & Interventions
Nivolumab Monotherapy
Nivolumab 240 mg IV every 2 weeks for maximum of 24 months. TTF (Optune) for max of 24 months
Intervention: Nivolumab 240 mg IV
Nivolumab Monotherapy
Nivolumab 240 mg IV every 2 weeks for maximum of 24 months. TTF (Optune) for max of 24 months
Intervention: NovoTTF200A (Optune)
Nivolumab+Ipilimumab
Nivolumab 3 mg/kg IV with ipilimumab then 240 mg every 2 weeks for maximum of 24 months. Ipilimumab 1 mg/kg IV every 6 weeks maximum of 4 times. NovoTTF200A (Optune) TTF for maximum 24 months
Intervention: Nivolumab 240 mg IV
Nivolumab+Ipilimumab
Nivolumab 3 mg/kg IV with ipilimumab then 240 mg every 2 weeks for maximum of 24 months. Ipilimumab 1 mg/kg IV every 6 weeks maximum of 4 times. NovoTTF200A (Optune) TTF for maximum 24 months
Intervention: Nivolumab 3 mg/kg
Nivolumab+Ipilimumab
Nivolumab 3 mg/kg IV with ipilimumab then 240 mg every 2 weeks for maximum of 24 months. Ipilimumab 1 mg/kg IV every 6 weeks maximum of 4 times. NovoTTF200A (Optune) TTF for maximum 24 months
Intervention: Ipilimumab 1 mg/kg
Nivolumab+Ipilimumab
Nivolumab 3 mg/kg IV with ipilimumab then 240 mg every 2 weeks for maximum of 24 months. Ipilimumab 1 mg/kg IV every 6 weeks maximum of 4 times. NovoTTF200A (Optune) TTF for maximum 24 months
Intervention: NovoTTF200A (Optune)
Outcomes
Primary Outcomes
Objective Response Rate According to Modified iRANO Criteria
Time Frame: 2 years
Objective response rate is the proportion of patients whose best overall response per modified immunotherapy response assessment in neuro-oncology (iRANO) criteria is complete (CR) or partial (PR) after at least 6 weeks from start of therapy
Secondary Outcomes
- Number of Toxicities(Up to 2 years)
- Rate of Treatment Compliance(Monthly for up to 2 years)
- Change in Quality of Life From Baseline Using the Functional Assessment of Cancer Therapy-Brain (FACT-Br)(Up to 2 years)
- Change in Quality of Life From Baseline Using the Functional Assessment of Cancer Therapy-General (FACT-G)(Up to 2 years)
- Objective Response Rate (ORR) by Standard RANO Criteria(2 years)
- Progression Free Survival (PFS)(2 years)
- Discontinuation Rate of Any Component of Therapy(Up to 2 years)