Phase I Trial of Hypofractionated Stereotactic Irradiation (HFSRT) Combined With Nivolumab, Ipilimumab and Bevacizumab in Patients With Recurrent High Grade Gliomas
Overview
- Phase
- Phase 1
- Intervention
- Hypofractionated Stereotactic Irradiation
- Conditions
- Malignant Glioma
- Sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Enrollment
- 33
- Locations
- 2
- Primary Endpoint
- Number of Participants with Treatment Related Adverse Events
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The main purpose of this study is to evaluate the safety, and tolerability of nivolumab, ipilimumab, and bevacizumab given in combination with hypofractionated stereotactic re-irradiation of recurrent high grade gliomas.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed diagnosis of World Health Organization (WHO) Grade III or IV malignant glioma.
- •Documented recurrence by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI) performed within 28 days of entry in to the trial as per Response Assessment in Neuro-Oncology (RANO) criteria.
- •Maximum diameter of enhancing tumor (target lesion) should be ≤ 4 cm.
- •An interval of at least 6 months after the end of prior radiation therapy is required unless there is a new recurrence outside of the previous radiotherapy treatment field.
- •Previous first line treatment with at least standard dose of radiotherapy (total dose ≥ 54 Gy) and temozolomide or Procarbazine, Lomustine, and Vincristine (PCV) for high grade glioma.
- •An interval of ≥ 4 weeks since surgical resection prior to start of study treatment.
- •An interval of ≥ 4 weeks after the last administration of any investigational agent, bevacizumab, or prior cytotoxic therapy.
- •≥18 years of age on day of signing informed consent.
- •Karnofsky performance status of 70 or higher.
- •Demonstrate adequate organ function. All screening labs should be performed within 28 days of treatment initiation.
Exclusion Criteria
- •Has more than three recurrences of high grade glioma. Previous recurrences of low grade glioma is not considered.
- •Has received re-radiation to recurrent disease (other than standard frontline adjuvant radiation therapy).
- •Recurrent tumors near the brainstem and optic chiasm must not have received prior radiation therapy.
- •Has infratentorial, or leptomeningeal evidence of recurrent disease.
- •Has recurrent or persistent tumor (enhancing area) greater than 4 cm in maximum diameter.
- •Has prior treatment with Gliadel unless it was administered as first line treatment and at least 3 months prior to study treatment.
- •Is unable (due to existent medical condition) or unwilling to have a contrast enhanced MRI of brain.
- •Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Low doses of steroid therapy (dexamethasone 2mg/day or ≤ 10 mg/day prednisone equivalents) is allowed.
- •Has had a prior chemotherapy, targeted small molecule therapy, or monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. This does not include lymphopenia.
Arms & Interventions
Combination Therapy
Safety Cohort: The first 6 participants will receive Hypofractionated Stereotactic Irradiation (HFSRT) followed by Ipilimumab + Nivolumab + Bevacizumab. Dose Expansion Cohort: All 26 participants will be treated with Hypofractionated Stereotactic Irradiation (HFSRT), followed by Ipilimumab + Nivolumab +Bevacizumab
Intervention: Hypofractionated Stereotactic Irradiation
Combination Therapy
Safety Cohort: The first 6 participants will receive Hypofractionated Stereotactic Irradiation (HFSRT) followed by Ipilimumab + Nivolumab + Bevacizumab. Dose Expansion Cohort: All 26 participants will be treated with Hypofractionated Stereotactic Irradiation (HFSRT), followed by Ipilimumab + Nivolumab +Bevacizumab
Intervention: Nivolumab
Combination Therapy
Safety Cohort: The first 6 participants will receive Hypofractionated Stereotactic Irradiation (HFSRT) followed by Ipilimumab + Nivolumab + Bevacizumab. Dose Expansion Cohort: All 26 participants will be treated with Hypofractionated Stereotactic Irradiation (HFSRT), followed by Ipilimumab + Nivolumab +Bevacizumab
Intervention: Bevacizumab
Combination Therapy
Safety Cohort: The first 6 participants will receive Hypofractionated Stereotactic Irradiation (HFSRT) followed by Ipilimumab + Nivolumab + Bevacizumab. Dose Expansion Cohort: All 26 participants will be treated with Hypofractionated Stereotactic Irradiation (HFSRT), followed by Ipilimumab + Nivolumab +Bevacizumab
Intervention: Ipilimumab
Outcomes
Primary Outcomes
Number of Participants with Treatment Related Adverse Events
Time Frame: Up to 24 months
Safety and tolerability of nivolumab, given in combination with hypofractionated stereotactic re-irradiation of recurrent high grade gliomas.
Secondary Outcomes
- Response Rate(Up to 36 months)
- Overall Survival (OS) Rate at 6 Months(6 months)
- Overall Survival (OS) Rate at 9 Months(9 months)