Ph I Personalized NeoAntigen Cancer Vaccine With Radiotherapy for Patients With MGMT Unmethylated, Newly Diagnosed Glioblastoma
This research study is studying a new type of vaccine as a possible treatment for patients with MGMT-unmethylated glioblastoma. This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the intervention to use for further studies. "Investigational" means that the intervention is being studied and that research doctors are trying to find more about it. It also means that the FDA (U.S. Food and Drug Administration) has not approved the Personalized NeoAntigen Cancer Vaccine for any use in patients, including people with glioblastoma.
The purpose of this study is to determine if it is possible to make and administer safely a vaccine against glioblastoma by using information gained from specific characteristics of the participants tumor. It is known that glioblastomas have mutations (changes in genetic material) that are specific to an individual patient's tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the body fight any tumor cells that could cause the glioblastoma to come back in the future.
|Glioblastoma MGMT-unmethylated Glioblastoma Gliosarcoma Glioblastoma With Oligodendroglial Features Giant Cell Glioblastoma Glioblastoma Multiforme||Radiation: Radiation Therapy Biological: Personalized NeoAntigen Vaccine||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase I Study of a Personalized NeoAntigen Cancer Vaccine With Radiotherapy Among MGMT Unmethylated, Newly Diagnosed Glioblastoma Patients|
- Number of participants with Adverse Events as a measure of safety and tolerability [ Time Frame: 2 Years ]We will be looking at adverse events (including DLTs) to evaluate safety and tolerability of administering NeoVax in participants with newly diagnosed glioblastoma.
- Number of participants with at least 10 actionable peptides as a measure of study feasibility [ Time Frame: 2 Years ]This information will be used to determine the feasibility of generating and administering NeoVax in participants with newly diagnosed glioblastoma.
- Number of participants who are clinically able to initiate post-RT vaccine therapy within 12 weeks or less from date of surgery as a measure of study feasibility [ Time Frame: 2 Years ]This information will be used to determine the feasibility of generating and administering NeoVax in participants with newly diagnosed glioblastoma.
- Number of participants who achieve IFN-γ T-cell response (more than 55 SFU/106 PBMC or 3 times their baseline level) at week 16 via ELISPOT assessments [ Time Frame: 2 Years ]This information will be used to assess the induction of neoantigen-specific cellular immune responses following administration of NeoVax.
- Number of participants who are alive without progression at eight months after surgery resection [ Time Frame: 2 Years ]Estimate of the proportion of participants alive without disease progression at eight months after resection. The endpoint will be calculated as the time between pathological confirmation of resection and the first of disease recurrence or death.
|Actual Study Start Date:||November 2014|
|Estimated Study Completion Date:||August 2018|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Personalized NeoAntigen Vaccine
After the screening procedures confirm participant eligible to participate in the research study (must be registered to within 6 weeks of resection):
After participant recovers from RT and vaccine is created, s/he will re-screen to confirm s/he is eligible to receive study vaccinations. Once registered, participant will proceed to receive study vaccinations:
- NeoAntigen Vaccine: NeoVax will be administered on an individual basis using a dosing schedule that incorporates both priming and boost phases (~ 7 months total: 5 priming followed by 2 boost vaccine administrations)
Radiation: Radiation Therapy
Standard radiotherapy (approximately 60 Gy over 6 weeks)Biological: Personalized NeoAntigen Vaccine
NeoVax will be administered on an individual basis using a dosing schedule that incorporates both priming and boost phases.
Other Name: NeoVax
It is known that glioblastomas have mutations that are specific to an individual patient's tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the body fight any tumor cells that could cause glioblastoma to recur.
Methylguanine methyltransferase (MGMT) is a DNA repair protein which can be increased in some cancers, including glioblastoma. MGMT works to repair the DNA of cancer cells that are damaged by treatment. If a tumor is found to be "unmethylated", it means there is more MGMT present in the tumor than one that is "methylated".
Methylation of MGMT is believed to make tumor cells more responsive to drugs like temozolomide. Studies have shown that temozolomide provides a very small improvement in outcome for many patients whose glioblastoma is MGMT-unmethylated. This study is for patients with MGMT-unmethylated glioblastoma.
Patients with glioblastoma usually receive six weeks of radiation with a daily chemotherapy called temozolomide after their surgery, followed by six to twelve months of additional temozolomide. In this study, participants will not take temozolomide, as their tumors are MGMT-unmethylated, and studies have shown that temozolomide provides a very small improvement in outcome for many patients whose glioblastoma is MGMT-unmethylated.
Instead, on this trial, participants will receive the Personalized NeoAntigen Vaccine after completing six weeks of radiation:
- Therapy On This Study:
- Followed by six weeks of radiation therapy
- Followed by a series of vaccine administrations (~ 7 months)
The study will examine the safety of the vaccine when given at several different time points and will examine the participant blood cells for signs that the vaccine induced an immune response.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02287428
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||David A. Reardon, MD||Dana-Farber Cancer Institute|