52 Participants Needed

Pembrolizumab + Standard Therapy for Glioblastoma

Recruiting at 2 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

Do I need to stop my current medications to join 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.

What data supports the effectiveness of the treatment Pembrolizumab + Standard Therapy for Glioblastoma?

Research shows that combining temozolomide (a chemotherapy drug) with radiotherapy can help control glioblastoma, a type of brain cancer. Additionally, immune checkpoint inhibitors like nivolumab, which are similar to pembrolizumab, have been studied for their potential to enhance the effects of standard treatments in glioblastoma.12345

Is the combination of Pembrolizumab and standard therapy for glioblastoma safe for humans?

Pembrolizumab (KEYTRUDA) has been approved for use in other conditions like metastatic melanoma, with common side effects including fatigue, cough, nausea, and rash. Temozolomide, used in brain tumors, has a good safety profile and is generally well tolerated. Combining these with radiation therapy has shown to be safe in various studies, although specific safety data for glioblastoma is limited.13678

What makes the treatment with pembrolizumab, radiation, and temozolomide unique for glioblastoma?

This treatment combines pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with radiation and temozolomide, a chemotherapy drug that makes cancer cells more sensitive to radiation. This combination aims to enhance the overall effectiveness against glioblastoma, which is typically resistant to standard treatments.123910

What is the purpose of this trial?

This phase II trial studies the side effects and how well pembrolizumab works in combination with standard therapy in treating patients with glioblastoma. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in the chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Giving pembrolizumab and standard therapy comprising of temozolomide and radiation therapy may kill tumor cells.

Research Team

IF

Ian F. Parney, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

Adults with confirmed glioblastoma or astrocytoma grade IV, who can provide consent and samples for research. They must have adequate organ function, no severe diseases that could interfere with the trial, not be pregnant or nursing, agree to use contraception if of childbearing potential, and be willing to return for follow-up. Excluded are those with recent heart issues, active autoimmune disease requiring treatment in the past 2 years (except certain conditions), current pneumonitis or infections, HIV on antiretroviral therapy, other cancers being treated within 5 years.

Inclusion Criteria

Albumin >= 2.5 mg/dL (obtained =< 28 days prior to registration)
Provide written informed consent
My cancer is a Grade IV IDH-mutant astrocytoma.
See 20 more

Exclusion Criteria

I have had skin cancer (not melanoma) or early-stage cervical cancer.
You have used or plan to use the Optune device.
I am currently breastfeeding.
See 18 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant

Patients receive pembrolizumab intravenously over 30 minutes on day 1

1 day
1 visit (in-person)

Surgery

Patients undergo standard of care surgery within days 4-7

1 week
1 visit (in-person)

Concurrent

Patients receive pembrolizumab and temozolomide, and undergo external beam radiation therapy

7 weeks
Multiple visits (in-person)

Adjuvant

Patients receive pembrolizumab and temozolomide in cycles, repeating every 63 days for up to 5 cycles

Up to 10 months
Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years
Every 3 months until progressive disease, then every 6 months

Treatment Details

Interventions

  • External Beam Radiation Therapy
  • Laboratory Biomarker Analysis
  • Pembrolizumab
  • Radiation Therapy
  • Temozolomide
  • Therapeutic Conventional Surgery
Trial Overview The trial is testing pembrolizumab combined with standard therapies including temozolomide chemotherapy and radiation therapy against glioblastoma tumors. Pembrolizumab is an immunotherapy drug designed to boost the body's immune response against cancer cells.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Group 2 (pembrolizumab, temozolomide, radiation therapy )Experimental Treatment5 Interventions
CONCURRENT (CYCLE 1): Starting 21-35 days after surgery, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 and temozolomide PO daily on days 8-54. Patients also undergo external beam radiation therapy every 5 days per week on days 8-54. ADJUVANT (CYCLES 2-6): Within 3-5 weeks after completing radiation therapy, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 of cycles 2-5 and 1 and 22 of cycle 6 (up to a total of 17 doses). Patients also receive temozolomide PO daily on days 1-5, 29-33, and 57-61 of cycles 2 and 6, days 22-26 and 50-54 of cycle 3, days 15-19 and 43-47 of cycle 4, days 8-12 and 36-40 of cycle 5. Treatment repeats every 63 days for up to 5 cycles in the absence of disease progression or unexpected toxicity.
Group II: Group 1 (pembrolizumab, surgery, temozolomide, radiation)Experimental Treatment6 Interventions
NEOADJUVANT (CYCLE 1): Patients receive pembrolizumab IV over 30 minutes on day 1. SURGERY (CYCLE 2): Patients undergo standard of care surgery within days 4-7. CONCURRENT (CYCLE 3): Starting 21-35 days after surgery, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 and temozolomide PO daily on days 8-54. Patients also undergo external beam radiation therapy every 5 days per week on days 8-54. ADJUVANT (CYCLE 4-8): Within 3-5 weeks after completing radiation therapy, patients receive pembrolizumab IV over 30 minutes on days 1, 22, and 43 and temozolomide PO daily on days 1-5 every 28 days. Treatment repeats every 63 days for up to 5 cycles in the absence of disease progression or unexpected toxicity.

External Beam Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

🇪🇺
Approved in European Union as External Beam Radiation Therapy for:
  • Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers
🇺🇸
Approved in United States as External Beam Radiation Therapy for:
  • Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers
🇨🇦
Approved in Canada as External Beam Radiation Therapy for:
  • Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers
🇯🇵
Approved in Japan as External Beam Radiation Therapy for:
  • Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers
🇨🇳
Approved in China as External Beam Radiation Therapy for:
  • Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers
🇨🇭
Approved in Switzerland as External Beam Radiation Therapy for:
  • Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Find a Clinic Near You

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials
3,427
Recruited
3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

Nivolumab combined with radiotherapy and temozolomide (NIVO+RT+TMZ) is tolerable for patients with newly diagnosed glioblastoma, with no new safety concerns identified; however, higher rates of grade 3/4 treatment-related adverse events were observed compared to Nivolumab with radiotherapy alone (NIVO+RT).
The study found that overall survival (OS) was similar for patients with unmethylated MGMT promoter whether they received NIVO+RT+TMZ or NIVO+RT, indicating that the addition of temozolomide may not significantly improve outcomes in this subgroup.
Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143.Omuro, A., Reardon, DA., Sampson, JH., et al.[2023]
In a phase III study involving 716 patients with newly diagnosed glioblastoma, the addition of the immune checkpoint inhibitor nivolumab (NIVO) to standard radiotherapy (RT) and temozolomide (TMZ) did not significantly improve progression-free survival (PFS) or overall survival (OS) compared to placebo, with median OS of 28.9 months for NIVO versus 32.1 months for placebo.
The study found a higher rate of grade 3/4 treatment-related adverse events in the NIVO group (52.4%) compared to the placebo group (33.6%), indicating that while NIVO did not enhance efficacy, it was associated with increased toxicity.
Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter.Lim, M., Weller, M., Idbaih, A., et al.[2023]
Temozolomide (TMZ) enhances the effectiveness of radiation therapy in treating glioblastoma cells, leading to a significant reduction in colony formation when combined with irradiation, compared to either treatment alone.
While irradiation was more toxic to glioma cells than TMZ, the combination of both treatments increased the sensitivity of glioma cells to radiation, suggesting a potential strategy for improving glioblastoma treatment outcomes.
Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay.Babaloui, S., Najafi, M., Mozdarani, H., et al.[2022]

References

Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143. [2023]
Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. [2023]
Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. [2022]
Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy. [2020]
Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial. [2018]
Temozolomide for treating brain metastases. [2019]
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]
Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal&#174;) in glioma patients in China. [2021]
Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. [2021]
Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. [2021]
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