Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma
- Conditions
- Glioblastoma
- Interventions
- Registration Number
- NCT03661723
- Lead Sponsor
- Dana-Farber Cancer Institute
- Brief Summary
This research study is studying pembrolizumab and re-irradiation as possible treatments for glioblastoma.
The drugs involved in this study are:
* Pembrolizumab
* Radiation
* Bevacizumab, an FDA-approved drug for treating recurrent glioblastoma multiforme (GBM)
- Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
How the Study Interventions work:
Pembrolizumab: Pembrolizumab has been studied in lab experiments and in other types of cancer, and information from these studies suggests that it may be beneficial in this type of cancer. Pembrolizumab is a drug (an antibody) that may treat cancer by working with the immune system.
The FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for this specific disease but it has been approved for other uses.
Radiation (Re-irradiation): Radiotherapy destroys cancer cells using radiation aimed at a cancer from a machine.
The FDA (the U.S. Food and Drug Administration) has approved re-irradiation as a treatment option for this disease.
Bevacizumab: Bevacizumab (also known as "Avastin") is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.
The FDA (the U.S. Food and Drug Administration) has approved bevacizumab as a treatment option for this disease.
In this research study, the investigators are looking to determine if this combination (pembrolizumab + re-irradiation) proves helpful in treating this cancer. If the participant has already been receiving bevacizumab, the participant will continue to receive this along with pembrolizumab and re-irradiation. By doing this, the investigators will look to determine if this combination (pembrolizumab and bevacizumab + re-irradiation) proves helpful in treating this cancer.
This study will also test the safety and tolerability of this combination (pembrolizumab + re-irradiation) when given alone or with bevacizumab
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Bevacizumab + Radiation Re-irradiation * Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks * Bevacizumab (15 mg/kg) will be administered intravenously (IV) once every 3 weeks * Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks Pembrolizumab + Radiation Re-irradiation * Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks * Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks Pembrolizumab + Bevacizumab + Radiation (lead-in) Re-irradiation * Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks. (De-escalation dosing frequencies = once every 4 weeks and once every 6 weeks.) * Bevacizumab (15 mg/kg) will be administered intravenously (IV) once every 3 weeks * Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks Pembrolizumab + Radiation (lead-in) Re-irradiation * Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks. (De-escalation dosing frequencies = once every 4 weeks and once every 6 weeks.) * Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks Pembrolizumab + Radiation (lead-in) Pembrolizumab * Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks. (De-escalation dosing frequencies = once every 4 weeks and once every 6 weeks.) * Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks Pembrolizumab + Bevacizumab + Radiation (lead-in) Pembrolizumab * Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks. (De-escalation dosing frequencies = once every 4 weeks and once every 6 weeks.) * Bevacizumab (15 mg/kg) will be administered intravenously (IV) once every 3 weeks * Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks Pembrolizumab + Bevacizumab + Radiation Pembrolizumab * Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks * Bevacizumab (15 mg/kg) will be administered intravenously (IV) once every 3 weeks * Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks Pembrolizumab + Bevacizumab + Radiation (lead-in) Bevacizumab * Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks. (De-escalation dosing frequencies = once every 4 weeks and once every 6 weeks.) * Bevacizumab (15 mg/kg) will be administered intravenously (IV) once every 3 weeks * Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks Pembrolizumab + Radiation Pembrolizumab * Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks * Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks Pembrolizumab + Bevacizumab + Radiation Bevacizumab * Pembrolizumab (200 mg) will initially be administered intravenously (IV) once every 3 weeks * Bevacizumab (15 mg/kg) will be administered intravenously (IV) once every 3 weeks * Re-irradiation (35 Gy) will be administered to patients 5 days per week for 2 weeks
- Primary Outcome Measures
Name Time Method Overall Survival Rate at 12 Months (OS-12) 12 months Overall Survival Rate at 6 Months (OS-6) 6 months Objective Response Rate (ORR) 2 years Per Response Assessment in Neuro-Oncology (RANO) Criteria:
* Complete Response (CR):
* Disappearance of all enhancing measurable \& non-measurable disease sustained for at least 4 weeks
* No new lesions
* Stable or improved non-enhancing (T2/FLAIR) lesions
* No corticosteroids (or physiologic replacement doses only)
* And stable or improved clinically
* Partial Response (PR):
* \>=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks;
* No progression of non-measurable disease
* No new lesions
* Stable or improved non-enhancing (T2/FLAIR) lesions
* Same or lower dose of corticosteroids compared with baseline scan
* And stable or improved clinically
Overall Response Rate (ORR) = Frequency of CR + PR within a population.
- Secondary Outcome Measures
Name Time Method Safety & Tolerability: SAEs Experienced by Participants 2 years Number of Participants who Experienced an SAE Deemed At Least Possibly Related to Study Treatment (XRT, pembrolizumab, \&/or bevacizumab)
Median Progression Free Survival (PFS) 2 years Progression is defined using Radiologic Assessment in Neuro-Oncology (RANO) criteria, as any of the following:
* ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement, on stable or increasing doses of corticosteroids
* Any new enhancing measurable lesion
* Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose
* Cohort B: Significant increase in T2/FLAIR non-enhancing lesions on stable or increasing doses of corticosteroids not felt to be caused by co-morbid events
* Clear progression of non-measurable disease
* Or failure to return for evaluation as a result of death or deteriorating conditionDuration of Response 1 year Each patient's response data is reviewed and the duration of his/her best response determined (in days).
6-month Progression Free Survival (PFS-6) 6 months Progression is defined using Radiologic Assessment in Neuro-Oncology (RANO) criteria, as any of the following:
* ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement, on stable or increasing doses of corticosteroids
* Any new enhancing measurable lesion
* Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose
* Cohort B: Significant increase in T2/FLAIR non-enhancing lesions on stable or increasing doses of corticosteroids not felt to be caused by co-morbid events
* Clear progression of non-measurable disease
* Or failure to return for evaluation as a result of death or deteriorating conditionMedian Overall Survival (OS) Participants were followed for survival until death; survival was followed for a max of 4 years. Other Adverse Events (AEs) were collected from registration through 30 days after last dose (SAEs through 90 days); AEs were followed for a max of 2 years.
Trial Locations
- Locations (5)
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Columbia University / Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Hospital of the University of Pennsylvania, Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States