Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM)

Summary

Background:

Glioblastoma (GBM) refers to a specific kind of brain cancer called glioblastoma. The standard treatment for GBM is radiation plus temozolomide, an oral chemotherapy drug. Pembrolizumab is an immune therapy that is now used to treat other cancers. The addition of pembrolizumab to the standard treatment of radiation and temozolomide has been shown to be well tolerated. Researchers want to see if adding a vaccine made from the person's own tumor will improve the effect of the pembrolizumab. The vaccine which is developed from fresh tumor taken at the time of surgery is called heat shock protein peptide complex-96 (HSPPC-96).

Objectives:

To see if the adding of pembrolizumab and HSPPC-96 improves the standard treatment for glioblastoma.

Eligibility:

Adults at least 18 years old with glioblastoma.

Design:

Participants will be screened with typical cancer tests:

Brain scan

Medical history

Blood and urine tests

Questions about quality of life and symptoms

These tests will be repeated throughout the study.

Participants will have surgery to remove their tumor. A tissue sample from the tumor will be sent to a lab. A vaccine will be made from it.

Some participants will get pembrolizumab and vaccine. Some will get pembrolizumab and placebo. Participants will not know which they get.

Participants will get radiation for 6 weeks.

Participants will take temozolomide by mouth before each treatment.

Participants will get pembrolizumab by intravenous (IV) for 30 minutes 3 times over the radiation cycle.

Participants will keep taking the 2 drugs every few weeks for about a year. Some may take pembrolizumab for an additional year.

Most participants will get the vaccine or placebo after radiation. They will get it 5 times over 6 weeks. Some participants will continue to get the vaccine every few weeks for 1 or 2 years.

Participants will repeat the screening tests when they stop study treatment. They will also have follow-up phone calls.

Conditions

• Glioblastoma

Interventions

DRUG

Pembrolizumab

Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy (RT) every 3 weeks during RT on days 1, 22 and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with heat shock protein peptide complex -96 (HSPPC 96) or placebo vaccine if any is available.

BIOLOGICAL

HSPPC-96

One week post RT, patients will receive weekly x 4 a dose of heat shock protein peptide complex -96 (HSPPC 96) 0.4mL intradermal vaccine or placebo. HSPPC-96 vaccine or placebo will then be given 21 days after the day 5 dose of temozolomide (TMZ). HSPPC-96 vaccine or placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available.

DRUG

Temozolomide

Temozolomide (TMZ) will be administered on day 1 of radiation therapy (before radiation therapy (RT) treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.

OTHER

Placebo

One week post radiation therapy (RT), participants will receive weekly x 4 a dose of heat shock protein peptide complex -96 (HSPPC 96) 0.4mL intradermal vaccine or placebo. HSPPC-96 vaccine or placebo will then be given 21 days after the day 5 dose of Temozolomide (TMZ). HSPPC-96 vaccine or placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 or placebo vaccine if any is available.

PROCEDURE

Surgery

Tissue for vaccine production and neo-epitope monitoring.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Kevin Camphausen, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-09-21

Primary Completion

2022-12-20

Completion

2022-12-20

FDA Drug

Yes

Countries

• United States

Study Locations