A Phase I Trial of Hypofractionated Stereotactic Irradiation (HFSRT) With Pembrolizumab and Bevacizumab in Patients With Recurrent High Grade Gliomas
Overview
- Phase
- Phase 1
- Intervention
- Hypofractionated Stereotactic Irradiation (HFSRT)
- Conditions
- Malignant Glioma
- Sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to see if the addition of the investigation drug called pembrolizumab (Keytruda®) to radiation therapy and bevacizumab (Avastin®) is safe and can help with controlling the growth of tumors, in participants with recurrent high grade glioma.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed diagnosis of World Health Organization (WHO) Grade III (except anaplastic oligodendroglioma) or IV malignant glioma.
- •Documented recurrence by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI) performed within 28 days of entry into the trial as per Response Assessment Criteria for High-Grade Gliomas (RANO) Criteria.
- •Patients with recurrent WHO Grade III gliomas should have received one prior treatment for recurrent high grade disease.
- •Maximum diameter of enhancing tumor (target lesion) should be ≤ 3.5 cm.
- •Interval of ≥ 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.
- •Interval of ≥ 4 weeks since surgical resection prior to entry into the trial.
- •Interval of ≥ 4 weeks after last administration of any investigational agent or prior cytotoxic therapy (except bevacizumab). There should be 14 days interval between the last dose of bevacizumab and first day of treatment on study.
- •Age 18 years or older on day of signing informed consent.
- •Karnofsky performance status ≥
Exclusion Criteria
- •More than 3 recurrences of high grade glioma.
- •Has anaplastic oligodendroglioma.
- •Has received reradiation 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.
- •Infratentorial, or leptomeningeal evidence of recurrent disease.
- •Recurrent or persistent tumor (enhancing area) greater than 3.5 cm in maximum diameter.
- •Prior treatment with Gliadel unless it was administered as first line treatment and ≥ 3 months prior to study treatment.
- •Unable (due to existent medical condition) or unwilling to have a contrast enhanced MRI of brain.
- •Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of treatment.
- •Diagnosis of immunodeficiency or is receiving systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Physiologic doses of steroid therapy (≤ 10 mg/day prednisone equivalents) is allowed.
Arms & Interventions
HFSRT with Pembrolizumab and Bevacizumab
Hypofractionated Stereotactic Irradiation (HFSRT). Pembrolizumab intravenous (IV) infusion every 3 weeks. Bevacizumab administered intravenously every 2 weeks.
Intervention: Hypofractionated Stereotactic Irradiation (HFSRT)
HFSRT with Pembrolizumab and Bevacizumab
Hypofractionated Stereotactic Irradiation (HFSRT). Pembrolizumab intravenous (IV) infusion every 3 weeks. Bevacizumab administered intravenously every 2 weeks.
Intervention: Pembrolizumab
HFSRT with Pembrolizumab and Bevacizumab
Hypofractionated Stereotactic Irradiation (HFSRT). Pembrolizumab intravenous (IV) infusion every 3 weeks. Bevacizumab administered intravenously every 2 weeks.
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD)
Time Frame: Up to 24 months
The pembrolizumab dose used in the dose expansion cohort will be MTD determined from the dose escalation phase. Dose Escalation: The maximum tolerated dose (MTD) is the highest dose of pembrolizumab in combination with bevacizumab after radiation therapy that does not cause unacceptable toxicity in more than one of six patients at that dose level. The MTD is defined as one dose level below the highest toxic dose (i.e., the Dose Limiting Toxicity (DLT) dose).
Secondary Outcomes
- Response Rate (RR)(Up to 24 months)