Ignite Creation Date:
2025-12-26 @ 11:00 AM
Ignite Modification Date:
2025-12-29 @ 6:34 PM
Study NCT ID:
NCT03197506
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-04-06
First Post:
2017-06-21
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pembrolizumab and Standard Therapy in Treating Patients With Glioblastoma
Sponsor:
Mayo Clinic
Organization:
Study Overview
Official Title:
Phase II Study of Pembrolizumab (MK-3475) in Combination With Standard Therapy for Newly Diagnosed Glioblastoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
Detailed Description:
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of pembrolizumab in combination with standard therapy (surgery, external beam radiation therapy and temozolomide \[TMZ\] chemotherapy) in patients with newly diagnosed glioblastoma multiforme (GBM). (Neoadjuvant \[Group 1\]) II. To assess the 18 month overall survival rate of pembrolizumab in combination with standard therapy (surgery, external beam radiation therapy and TMZ chemotherapy) in patients with newly diagnosed glioblastoma multiforme (GBM). (Adjuvant \[Group 2\])
SECONDARY OBJECTIVES:
I. To assess adverse events (AE) and toxicity profile of pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM.
II. To assess time to progression in patients treated with pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM. (Adjuvant only) III. To assess progression-free survival in patients treated with pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM. (Adjuvant only) IV. To assess time to treatment failure in patients treated with pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM. (Adjuvant only)
CORRELATIVE RESEARCH OBJECTIVES:
I. To assess the tumor PD-1/PD-L1 expression and inflammatory microenvironment profile by comparing PD-1/PD-L1 expression and T lymphocyte/monocytic infiltrates before and after administration of pembrolizumab treatment. (Neoadjuvant only) II. To assess the peripheral immunophenotype profile and GBM-associated antigen-specific T cell responses before and after receiving pembrolizumab treatment in combination with standard therapy.
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP 1:
NEOADJUVANT (CYCLE 1): Patients receive pembrolizumab intravenously (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 orally (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.
GROUP 2:
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.
After completion of study treatment, patients are followed up at 30 days, every 3 months until progressive disease, then every 6 months for up to 5 years.
I. To assess the safety and tolerability of pembrolizumab in combination with standard therapy (surgery, external beam radiation therapy and temozolomide \[TMZ\] chemotherapy) in patients with newly diagnosed glioblastoma multiforme (GBM). (Neoadjuvant \[Group 1\]) II. To assess the 18 month overall survival rate of pembrolizumab in combination with standard therapy (surgery, external beam radiation therapy and TMZ chemotherapy) in patients with newly diagnosed glioblastoma multiforme (GBM). (Adjuvant \[Group 2\])
SECONDARY OBJECTIVES:
I. To assess adverse events (AE) and toxicity profile of pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM.
II. To assess time to progression in patients treated with pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM. (Adjuvant only) III. To assess progression-free survival in patients treated with pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM. (Adjuvant only) IV. To assess time to treatment failure in patients treated with pembrolizumab in combination with standard therapy in patients with newly diagnosed GBM. (Adjuvant only)
CORRELATIVE RESEARCH OBJECTIVES:
I. To assess the tumor PD-1/PD-L1 expression and inflammatory microenvironment profile by comparing PD-1/PD-L1 expression and T lymphocyte/monocytic infiltrates before and after administration of pembrolizumab treatment. (Neoadjuvant only) II. To assess the peripheral immunophenotype profile and GBM-associated antigen-specific T cell responses before and after receiving pembrolizumab treatment in combination with standard therapy.
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP 1:
NEOADJUVANT (CYCLE 1): Patients receive pembrolizumab intravenously (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 orally (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.
GROUP 2:
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.
After completion of study treatment, patients are followed up at 30 days, every 3 months until progressive disease, then every 6 months for up to 5 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: