Chemoimmunotherapy for Glioblastoma

Overseen By Donald Miller, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Louisville

Must be taking: Temozolomide

Must not be taking: Immunotherapy

Disqualifiers: Prior malignancy, Stroke, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 13

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of combining two drugs, Pembrolizumab (an immunotherapy drug known as KEYTRUDA) and Temozolomide (a chemotherapy drug), to treat glioblastoma, a type of brain tumor that has returned after previous treatment. Researchers aim to observe how this combination affects both the tumor and the body's immune system. It may suit individuals who have already undergone standard chemoradiation (a mix of chemotherapy and radiation therapy) for glioblastoma and are experiencing a recurrence. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering the opportunity to be among the first to receive this combination therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the FDA has approved temozolomide for treating certain brain cancers. However, about 49% of patients have experienced serious side effects, such as tiredness and seizures. Understanding these potential risks is important before joining a trial.

Safety information for pembrolizumab is also available. Studies indicate it is generally well-tolerated when combined with other treatments, with few serious side effects reported in some trials. This suggests it might be safe for treating brain tumors like glioblastoma.

Both temozolomide and pembrolizumab have undergone previous studies, but their combined safety in this specific trial is still under investigation. Consulting medical professionals to understand the risks involved is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using pembrolizumab and temozolomide for glioblastoma because they offer a fresh approach compared to traditional therapies like surgery, radiation, and standard chemotherapy. Pembrolizumab is an immunotherapy drug that boosts the immune system to specifically target and attack cancer cells, offering a new mechanism of action that differs from conventional treatments. Temozolomide, on the other hand, is a chemotherapy pill that patients can conveniently take at home, targeting cancer cells by interfering with their DNA. This combination of chemoimmunotherapy could potentially enhance treatment effectiveness by harnessing both immune system activation and direct cancer cell attack.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

This trial will compare the effects of temozolomide and pembrolizumab as separate treatments for glioblastoma. Research has shown that using temozolomide with radiation can extend the lives of glioblastoma patients. In some studies, patients taking temozolomide had significantly better survival rates than those receiving only radiation. Specifically, 53.3% of patients with recurrent glioblastoma experienced disease stabilization or improvement with temozolomide.

For pembrolizumab, another treatment option in this trial, results in glioblastoma patients have been mixed. Some studies found that 37.7% of patients did not experience disease progression after six months and lived for an average of 13.1 months. However, other studies showed it was less effective when combined with other treatments. Both temozolomide and pembrolizumab work in different ways to combat cancer. ^{4 5 6 7 8}

Who Is on the Research Team?

Donald Miller, MD

Principal Investigator

University of Louisville/James Graham Brown Cancer Ctr.

Are You a Good Fit for This Trial?

This trial is for adults with confirmed glioblastoma, limited to the brain's upper part, who have completed standard chemoradiation. They must have adequate blood counts and organ function, no more than three prior treatments for high-grade glioma, and be able to consent. Women of childbearing age must test negative for pregnancy and use birth control; men also need contraception.

Inclusion Criteria

I have had 3 or fewer treatments for my high-grade brain tumor.

The original tumor sample from my diagnosis is available for review.

History/physical examination within 7 days prior to registration

Exclusion Criteria

I have previously received immunotherapy, like a vaccine or dendritic cell vaccine.

I have not had cancer (other than non-melanoma skin cancer) in the last 3 years.

Severe, active co-morbidity: Transmural myocardial infarction or unstable angina within the last 6 months prior to registration, History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to registration, Significant vascular disease, Known history of Tuberculosis or acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration, Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration, Patients with active autoimmune disease or history of autoimmune disease that might recur, Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy, Is pregnant or breastfeeding, Has received prior therapy with an anti-Programmed Death 1 (PD-1), anti- Programmed Death-ligand 1 (PD-L1), or anti- Programmed Death-ligand 1 (PD-L2) agent, Patient must have < 1.5 cm midline shift pre-operative, History of severe hypersensitivity reaction to any monoclonal antibody including pembrolizumab, Patients who cannot safely undergo MRI due to non-MRI compatible pacemaker, or other reason

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Treatment

Participants receive one cycle of Temozolomide and Pembrolizumab prior to tumor removal

3 weeks

1 visit (in-person)

Post-surgical Treatment

Participants receive three weekly cycles of Temozolomide and Pembrolizumab until progression

9 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Temozolomide

Trial Overview The study tests Pembrolizumab combined with Temozolomide's safety in treating recurrent glioblastoma. It aims to understand how this combination affects the tumor and immune system of participants.

How Is the Trial Designed?

Group I: temozolomide Experimental Treatment 1 Intervention

Participants will take Temozolomide pills at home at a dose determined by body weight. They will take the pills for five days every 3 weeks. It will be dispensed by the pharmacy and must be stored in a closed container at room temperature, away from heat, moisture, and direct light and kept from freezing. It will be kept out of the reach of children. Outdated medicine or medicine no longer needed will be returned to the Brown Cancer Center pharmacy for disposal.

Group II: Pembrolizumab Experimental Treatment 1 Intervention

Pembrolizumab will be administered at a dose of 200 mg as an IV infusion through a freely flowing IV. The diluted solution will be administered intravenously over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or add-on filter. Other drugs will not be co-administered through the same infusion line. Pembrolizumab doses will be repeated every three weeks.

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666634025001357

Efficacy and safety of adjuvant TTFields plus ... Among 23 WT-IDH GBM patients, median PFS and OS were 10.8 months (95% CI 7.4–16.6) and 20.5 months (95% CI 12.5–25.5), respectively (Figure 1C).

2. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.33378

Treatment with pembrolizumab in programmed death ligand 1 ... Results from this small, single-arm study demonstrating a 37.7% PFS rate at 6 months, median OS of 13.1 months, and DOR >8 months indicate ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11711056/

Pembrolizumab efficacy in a tumor mutation burden‐high ... The rapid disease progression, indicated by 80% Ki67 positivity, was markedly countered by the positive outcome of pembrolizumab treatment. This ...

4. nature.com nature.com/articles/s41423-024-01226-x

Immunotherapy for glioblastoma: current state, challenges ... Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7158647/

Window-of-opportunity clinical trial of pembrolizumab in ... Median progression-free survival (PFS) was 4.5 months (95% CI: 2.27, 6.83), and the 6-month PFS rate was 40%. Median overall survival (OS) was ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02311582

NCT02311582 | MK-3475 in Combination With MRI-guided ... The blood brain barrier (BBB) is a major obstacle to drug delivery in the treatment of malignant brain tumors including glioblastoma multiforme (GBM).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8284901/

Randomized Phase II and Biomarker Study of ... VEGF is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase II study of pembrolizumab alone or with bevacizumab in ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03197506

Pembrolizumab and Standard Therapy in Treating Patients ... This phase II trial studies the side effects and how well pembrolizumab works in combination with standard therapy in treating patients with glioblastoma.