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PARP Inhibitor

Pembro + Olaparib with TMZ for Recurrent Glioblastoma

Phase 2
Recruiting
Led By Luis N Gonzalez Castro, MD
Research Sponsored by Patrick Wen, MD
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Participants must be able to swallow oral medications.
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.
Must not have
Participant received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF0], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 28 days prior to the first dose of study intervention.
Participants who have received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 24 months
Awards & highlights

Summary

This trial is studying a combination of drugs as a possible treatment for recurrent glioblastoma (GBM), a brain tumor.

Who is the study for?
This trial is for adults with recurrent glioblastoma, a type of brain tumor. They must be in good physical condition (KPS ≥ 70), not pregnant or breastfeeding, able to swallow pills, and have adequate organ function. Patients should be at their first or second relapse and haven't had certain prior treatments like anti-PD-1 or PARP inhibitors.Check my eligibility
What is being tested?
The study tests a combination therapy using Pembrolizumab, Olaparib, and Temozolomide as potential treatments for recurrent glioblastoma. It aims to see if this mix can stop the tumor from growing after previous treatment has failed.See study design
What are the potential side effects?
Possible side effects include immune system reactions that might affect organs, fatigue, nausea, blood-related issues such as anemia or clotting problems. Each patient may experience these differently.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I can swallow pills.
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My brain tumor is a Grade IV glioblastoma without IDH mutation.
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I am at least 18 years old.
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I am not pregnant or breastfeeding.
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I am mostly independent and can carry out daily activities.
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I am mostly independent and can carry out daily activities.
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My brain tumor is a Grade IV glioblastoma without IDH mutation.
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My brain cancer has returned for the first or second time.
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My latest MRI shows my tumor has grown.
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I do not have another cancer that is getting worse or needs treatment.
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I can swallow pills.
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My MRI shows my tumor has grown according to specific criteria.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I have not received any colony-stimulating factors in the last 28 days.
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I have previously received immunotherapy targeting specific immune checkpoints.
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I am not taking medication that strongly affects enzyme CYP3A.
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My cancer has spread to the lining of my brain or other parts of my body.
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I have been diagnosed with an immunodeficiency or HIV.
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I am currently taking blood thinners like warfarin.
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I am allergic to medications similar to olaparib, temozolomide, or pembrolizumab.
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I haven't taken high doses of steroids like dexamethasone (>2 mg/day) for 3 days in a row within the last 2 weeks.
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I have a history of lung inflammation not caused by an infection.
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I have a heart condition that is currently causing symptoms.
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I have had viral therapy or vaccines for my brain tumor.
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I do not have any ongoing serious illnesses that could interfere with the study.
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My tumor is mainly in my brainstem or spinal cord.
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I have an active infection needing treatment or a known viral infection like HIV or hepatitis.
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My tumor has a 1p/19q co-deletion.
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I have an autoimmune disease treated with medication in the last 2 years.
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I have or might have a blood disorder related to MDS or AML.
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I have an active tuberculosis infection.
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I have been treated with drugs targeting blood vessel growth in cancer.
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I have previously been treated with a PARP inhibitor.
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I am currently taking medication for epilepsy.
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My cancer has an IDH mutation.
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I haven't taken immune-weakening drugs (except steroids) in the last 6 months.
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I have moderate to severe diarrhea.
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I have a history of heart problems.
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I haven't had serious bleeding or blood clotting issues in the past year.
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I am currently using herbal medications.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~24 months
This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
6-month Progression-Free Survival (PFS6)
Tumor infiltrating lymphocytes (TIL) Density
Secondary outcome measures
Gene expression profiling (GEP) score
Grade 3 or Higher Treatment-Related Toxicity Rate
Median Overall Survival (OS)
+1 more

Side effects data

From 2024 Phase 2 trial • 57 Patients • NCT03004183
21%
Fatigue
13%
Nausea
11%
Back pain
9%
Shortness of Breath
9%
Anemia
9%
Abdominal pain
9%
Diarrhea
7%
Pneumonia
7%
Kidney Injury and/or Infection
7%
Dyspnea
7%
Weight Loss
5%
Pneumothorax
5%
Malnutrition, Hypercalcemia and Weakness
5%
Intractable pain, back pain, hip pain
5%
Activated partial thromboplastin time prolonged
4%
Pleural effusion
4%
Atrial fibrillation with rapid ventricular response
2%
Thrombocytopenia
2%
Respiratory failure
2%
Skin rash
2%
colitis
100%
80%
60%
40%
20%
0%
Study treatment Arm
Single Arm

Trial Design

3Treatment groups
Experimental Treatment
Group I: Cohort 2 (Surgical Cohort): Arm B - Pembrolizumab monotherapyExperimental Treatment1 Intervention
Cohort 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).
Group II: Cohort 2 (Surgical Cohort): Arm A - Pembrolizumab plus olaparib and temozolomideExperimental Treatment3 Interventions
Cohort 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).
Group III: Cohort 1 (Safety Lead In): pembrolizumab plus olaparib and temozolomideExperimental Treatment3 Interventions
Following 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).
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Temozolomide
2010
Completed Phase 3
~1930
Pembrolizumab
2017
Completed Phase 2
~2010
Olaparib
2007
Completed Phase 4
~2210

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Pembrolizumab, a PD-1 inhibitor, enhances the immune system's ability to attack tumor cells by blocking the PD-1 pathway, which cancer cells use to evade immune detection. Olaparib, a PARP inhibitor, prevents cancer cells from repairing their DNA, leading to cell death, especially in cells with existing DNA repair deficiencies. Temozolomide, an alkylating agent, damages the DNA of cancer cells, preventing their replication and leading to cell death. These treatments are significant for Glioblastoma patients as they target the cancer cells' growth and survival mechanisms, potentially improving outcomes in this aggressive and challenging disease.

Find a Location

Who is running the clinical trial?

Patrick Wen, MDLead Sponsor
2 Previous Clinical Trials
313 Total Patients Enrolled
2 Trials studying Glioblastoma
313 Patients Enrolled for Glioblastoma
L. Nicolas Gonzalez Castro, MD, PhDLead Sponsor
Patrick Y. Wen, MDLead Sponsor
9 Previous Clinical Trials
703 Total Patients Enrolled
7 Trials studying Glioblastoma
618 Patients Enrolled for Glioblastoma

Media Library

Olaparib (PARP Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT05463848 — Phase 2
Glioblastoma Research Study Groups: Cohort 2 (Surgical Cohort): Arm A - Pembrolizumab plus olaparib and temozolomide, Cohort 2 (Surgical Cohort): Arm B - Pembrolizumab monotherapy, Cohort 1 (Safety Lead In): pembrolizumab plus olaparib and temozolomide
Glioblastoma Clinical Trial 2023: Olaparib Highlights & Side Effects. Trial Name: NCT05463848 — Phase 2
Olaparib (PARP Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT05463848 — Phase 2
~12 spots leftby Dec 2024
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