Surgical Pembro +/- Olaparib w TMZ for rGBM
A Surgical "Window-of-Opportunity" and Phase II Trial of Pembrolizumab, Olaparib and Temozolomide in Recurrent Glioblastoma
2 other identifiers
interventional
78
1 country
4
Brief Summary
This research study is studying a combination therapy as a possible treatment for recurrent glioblastoma (GBM), a brain tumor that is growing or progressing despite earlier treatment. The names of the study interventions involved in this study are/is:
- Pembrolizumab
- Olaparib
- Temozolomide (Temodar)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2022
Typical duration for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 12, 2022
CompletedFirst Posted
Study publicly available on registry
July 19, 2022
CompletedStudy Start
First participant enrolled
October 21, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2027
March 4, 2026
March 1, 2026
3.8 years
July 12, 2022
March 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Tumor infiltrating lymphocytes (TIL) Density
TIL density quantifies anti-tumor immune response. It is measured in tumor tissue from protocol surgery, analyzed by immunohistochemistry and by next generation sequencing.
At surgery. Surgery will occur 14 days +/- 5 days after initiation of treatment.
6-month Progression-Free Survival (PFS6)
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. PD defined by modified RANO as well as iRANO criteria, per protocol section 12.
6 months after surgery. Surgery will occur 14 days +/- 5 days after initiation of treatment.
Secondary Outcomes (4)
Objective Response Rate (ORR)
24 months
Median Overall Survival (OS)
24 months
Grade 3 or Higher Treatment-Related Toxicity Rate
24 months
Gene expression profiling (GEP) score
At surgery. Surgery will occur 14 days +/- 5 days after initiation of treatment.
Study Arms (3)
Cohort 1 (Safety Lead In): pembrolizumab plus olaparib and temozolomide
EXPERIMENTALFollowing a 3 + 3 dose escalation design 6-18 participants will receive: * Olaparib 2x daily on Days 1-7 of each 21-day study cycle. * Temozolomide 1x daily on Days 1-7 of each 21-day study cycle. * Pembrolizumab on Day 1 of every other 21-day cycle (once every 6 weeks).
Cohort 2 (Surgical Cohort): Arm A - Pembrolizumab plus olaparib and temozolomide
EXPERIMENTALCohort 2 participants will be randomized into either group a or b (1:1): Group A participants will receive pembrolizumab, olaparib, and temozolomide before and after surgery. * Olaparib 2x daily on Days 1-7 of each 21-day study cycle. * Temozolomide 1x daily on Days 1-7 of each 21-day study cycle. * Pembrolizumab on Day 1 of every other 21-day cycle (once every 6 weeks).
Cohort 2 (Surgical Cohort): Arm B - Pembrolizumab monotherapy
EXPERIMENTALCohort 2 participants will be randomized into either group a or b (1:1): Group B participants will receive pembrolizumab monotherapy before and after surgery. * Pembrolizumab Before Surgery: Day 1 of the pre-surgical treatment cycle. * Pembrolizumab After Surgery: Day 1 of every other 21-day cycle (once every 6 weeks).
Interventions
Intravenous infusion
Pill taken by mouth
Pill taken by mouth
Eligibility Criteria
You may qualify if:
- Participants must be able to understand and willing to sign a written informed consent document.
- Participants must be able to adhere to the dosing and visit schedules and agree to record medication times accurately and consistently in a daily diary.
- Participants must be at least 18 years old on day of signing informed consent.
- Women of childbearing potential are eligible to participate if they are not pregnant or breastfeeding.
- Participants must have a Karnofsky Performance Status (KPS) ≥ 70 and Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 (see Appendix A).
- Participants must be able to swallow oral medications. Nature of illness and treatment history
- Participants must have histologically World Health Organization Grade IV IDH wildtype glioblastoma by IDHR132H immunohistochemistry or variants including gliosarcoma or IDH wildtype diffuse glioma with molecularly features of glioblastoma (EGFR amplification, TERT promoter mutation, or concurrent gain of Chromosome 7 and loss of Chromosome 10) (Brat et al., 2018). IDH mutational status can be established via immunohistochemistry and/or next-generation sequencing.
- Participants must be at first or second relapse of GBM. First relapse is defined as progression following initial therapy and second relapse is progression following second therapy. The intent therefore is that patients had no more than 2 prior therapies (i.e. radiation +/- chemotherapy if that was used as initial therapy and one additional therapy for first recurrence). If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered to constitute 1 relapse.
- Participants must have shown unequivocal evidence for tumor progression by MRI scan per modified RANO criteria (Ellingson et al., 2017).
- MRI should be obtained within 14 days prior to study registration.
- Confirmation of availability of sufficient tissue from a prior surgery demonstrating glioblastoma for correlative studies is required prior to enrollment.
- Cohort 1: 15 unstained FFPE sections (standard 10 micrometer thickness)
- Cohort 2: 1 (FFPE) block (preferred) OR 35 unstained FFPE sections (standard 5 micrometer thickness)
- NOTES:
- If the above-mentioned tissue is not available from the most recent surgery revealing GBM, participants may be enrolled with tissue available from any prior surgery revealing GBM with prospective approval from the Principal Investigator.
- +6 more criteria
You may not qualify if:
- weeks or 5 half-lives (whichever is shorter) from any investigational agent;
- weeks from cytotoxic therapy (except 23 days for temozolomide; 6 weeks from nitrosoureas);
- weeks or 5 half-lives (whichever is shorter) from antibodies;
- weeks or 5 half-lives (whichever is shorter) from other anti-tumor therapies.
- No washout required for tumor treating fields.
- Clinical labs - Participants should have adequate organ function, in accordance to the studies outlined below. All screening laboratory tests should be performed within 10 days prior to the first dose of the study intervention.
- Hematology:
- Leukocytes ≥ 3,000/µL
- Absolute neutrophil count (ANC) ≥ 1,500/µL
- Platelet count ≥ 100,000/µL
- Absolute Lymphocyte Count ≥ 500/µL
- Hemoglobin ≥ 9.0 g/dL
- Biochemistry:
- AST (SGOT) and ALT (SGPT) ≤ 2.5 x institution's ULN (or ≤ 5 X institutional ULN for subjects with Gilberts syndrome)
- Serum bilirubin ≤ 1.5 x institution's ULN or direct bilirubin ≤ institutional ULN for subjects with total bilirubin levels \> 1.5 institutional ULN.
- +67 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- L. Nicolas Gonzalez Castro, MD, PhDlead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (4)
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Luis N Gonzalez Castro, MD
Dana-Farber Cancer Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Sponsor-Investigator
Study Record Dates
First Submitted
July 12, 2022
First Posted
July 19, 2022
Study Start
October 21, 2022
Primary Completion (Estimated)
August 1, 2026
Study Completion (Estimated)
March 1, 2027
Last Updated
March 4, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.