GP96 Heat Shock Protein-Peptide Complex Vaccine in Treating Patients With Recurrent or Progressive Glioma
- Conditions
- Brain and Central Nervous System Tumors
- Interventions
- Biological: HSPPC-96Procedure: Standard Surgical Resection
- Registration Number
- NCT00293423
- Lead Sponsor
- University of California, San Francisco
- Brief Summary
Vaccines made from a person's tumor cells, such as gp96 heat shock protein-peptide complex, may help the body build an effective immune response to kill tumor cells. This phase I/II trial is studying the side effects and best dose of gp96 heat shock protein-peptide complex vaccine to see how well it works in treating patients with recurrent or progressive high-grade glioma over time.
- Detailed Description
PRIMARY OBJECTIVES:
* Phase 1: \[closed to accrual as of 7/25/2007\]: Determine the safety and best tolerated dose and frequency of gp96 heat shock protein-peptide complex vaccine in patients with recurrent or progressive high-grade glioma.
* Phase 2: Determine the clinical response to treatment, time to disease recurrence and progression, and overall survival of patients treated with this vaccine.
SECONDARY OBJECTIVES:
* Determine the immune response in patients treated with this vaccine.
* Determine survival outcomes in patients treated with this vaccine.
OUTLINE: This is a dose-escalation, phase I study (closed to accrual as of 7/25/2007) followed by a phase II study.
PHASE I \[closed to accrual as of 7/25/2007\]:
Patients underwent surgical resection. Viable tumor tissue is used to generate the gp96 heat shock protein-peptide complex (HSPPC-96) vaccine. Patients with primary disease receive standard adjuvant therapy after surgery. Patients whose disease progresses during or after standard adjuvant therapy receive the HSPPC-96 vaccine. Patients with recurrent disease receive the HSPPC-96 vaccine between 2-8 weeks after surgery. The HSPPC-96 vaccine is administered intradermally every 1-3 weeks for at least 4 doses and then every 2-3 weeks thereafter in the absence of disease progression, unacceptable toxicity, or vaccine depletion. Cohorts of 6 patients received the HSPPC-96 vaccine at escalating dose frequencies until the maximum tolerated dose (MTD) was determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experienced a dose-limiting toxicity.
PHASE II: Patients received the HSPPC-96 vaccine as in phase I at the appropriate dose frequency determined in phase I (closed to accrual as of 7/25/2007). The HSPPC-96 vaccine is administered intradermally every 1-3 weeks for at least 4 doses and then every 2 weeks thereafter in the absence of disease progression, unacceptable toxicity, or vaccine depletion. After completion of study treatment, patients are followed periodically until death, lost to follow-up, or end of study.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 96
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1: Vaccine HSPPC-96 Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections. Phase 1: Vaccine Standard Surgical Resection Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections. Phase 2: Vaccine Standard Surgical Resection Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection. Phase 2: Vaccine HSPPC-96 Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.
- Primary Outcome Measures
Name Time Method Median Progression-free Survival at 6 Months (Phase 2) 6 months Frequency of gp96 Heat Shock Protein-peptide Complex Vaccine (Phase 1) Up to 6 months The frequency of dosing of the first 4 injections to be recommended for Phase 2 will be determined by reviewing the reported number of dose-limiting toxicities for weekly or bi-weekly injections.
Maximum Tolerated Dose (MTD) (Phase 1) Up to 4 weeks MTD determination will be based on the occurrence of dose-limiting toxicities. The MTD will be 1 dose below the dose that defined the dose-limiting toxicities
Number of Participants With Dose Limiting Toxicities (Phase 1) Up to 4 weeks Systemic toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Dose-limiting toxicity is defined as any of the following that are attributable to vaccine therapy: Any grade 3, 4 or 5 toxicity, Any grade \>=2 clinical autoimmunity with the potential to threaten critical organs (including lungs, heart, kidney, bowel, bone marrow, liver or central nervous system (CNS), or eyes), and any removal of a patient from therapy due to toxicity
Percentage of Participants With Progression-free Survival at 12 Months (Phase 2) Up to 12 months Defined as the percentage of participants with confirmed response and who have not progressed from date of surgical resection until death or censored at 12 months
- Secondary Outcome Measures
Name Time Method Number of Patients With an Immunological Response (Phase 1) Up to 12 months An immunological response is defined as an absolute lymphocyte count (ALC) less than the lower limit of normal (1.0 × 109cells/L), according to the standard laboratory reference range
Percentage of Participants Surviving at 12 Months (Phase 2) Up to 12 months Defined as the percentage of participants still alive from date of surgical resection until death or censored at 12 months
Number of Patients With an Immunological Response (Phase 2) Up to 2 years An immunological response is defined as an absolute lymphocyte count (ALC) less than the lower limit of normal (1.0 × 109cells/L), according to the standard laboratory reference range
Number of Participants With Grade 3 or Higher, Vaccine Treatment-Related Adverse Events by Toxicity (Phase 2) Up to 2 years Vaccine treatment-related Adverse Events with a grade \>=3 according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be reported.
Median Overall Survival (Phase 2) Up to 2 years Overall survival is defined as the length of time from date of surgical resection until death or censored at end of study period
Percentage of Participants Surviving at 6 Months (Phase 2) Up to 6 months Defined as the percentage of participants still alive from date of surgical resection until death or censored at 6 months
Trial Locations
- Locations (3)
Columbia University
🇺🇸New York, New York, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States