GP96 Heat Shock Protein-Peptide Complex Vaccine in Treating Patients With Recurrent or Progressive Glioma

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I/II Trial of Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine for Patients With Recurrent High Grade Glioma

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: HSPPC-96
* Procedure: Standard Surgical Resection


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant recurrent glioma*, including any of the following: Glioblastoma Glioblastoma multiforme Recurrent disease or progressive primary disease Surgically accessible tumor for which surgical resection is indicated and has not been previously irradiated Prior radiotherapy required No prior oncophage therapy or immunotherapy for glioma PATIENT CHARACTERISTICS: Karnofsky performance status 80-100% Life expectancy ≥ 8 weeks Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Alkaline phosphatase and serum glutamic-pyruvic transaminase (SGPT) <=2.5 times normal Bilirubin < 1.5 mg/dL Blood Urea Nitrogen (BUN) < 1.5 times normal OR creatinine < 1.5 times normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for at least 4 weeks after completion of study treatment No uncontrolled active infection No bleeding diathesis No psychiatric or medical situation that would preclude study compliance No unstable or severe concurrent medical condition No other cancer or concurrent malignancy within the past 5 years except adequately treated nonmetastatic in situ carcinoma of the uterine cervix, nonmetastatic nonmelanoma skin cancer, or in complete remission and off all therapy for that disease No systemic autoimmune disease (e.g., Hashimoto's thyroiditis) and/or any history of primary or secondary immunodeficiency PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 2 weeks since prior vincristine At least 6 weeks since prior nitrosoureas At least 4 weeks since prior temozolomide or other cytotoxic chemotherapy At least 4 weeks since prior investigational agents At least 1 week since prior noncytotoxic agents At least 3 weeks since prior procarbazine No radiotherapy within the past 4 weeks

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Vaccine<br>Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections. | Biological: HSPPC-96<br>* 25 mcg<br>* Other names: Gp96;Procedure: Standard Surgical Resection<br>* Patients will undergo standard surgical resection of intracranial tumor<br>* Other names: Craniotomy;|
| Experimental: Phase 2: Vaccine<br>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. | Biological: HSPPC-96<br>* 25 mcg<br>* Other names: Gp96;Procedure: Standard Surgical Resection<br>* Patients will undergo standard surgical resection of intracranial tumor<br>* Other names: Craniotomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) (Phase 1) | 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 | Up to 4 weeks | 
| Frequency of gp96 Heat Shock Protein-peptide Complex Vaccine (Phase 1) | 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. | Up to 6 months | 
| Number of Participants With Dose Limiting Toxicities (Phase 1) | 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 | Up to 4 weeks | 
| Median Progression-free Survival at 6 Months (Phase 2) |  | 6 months | 
| Percentage of Participants With Progression-free Survival at 12 Months (Phase 2) | 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 | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With an Immunological Response (Phase 1) | 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 | Up to 12 months | 
| Number of Patients With an Immunological Response (Phase 2) | 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 | Up to 2 years | 
| Number of Participants With Grade 3 or Higher, Vaccine Treatment-Related Adverse Events by Toxicity (Phase 2) | 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. | Up to 2 years | 
| Median Overall Survival (Phase 2) | Overall survival is defined as the length of time from date of surgical resection until death or censored at end of study period | Up to 2 years | 
| Percentage of Participants Surviving at 6 Months (Phase 2) | Defined as the percentage of participants still alive from date of surgical resection until death or censored at 6 months | Up to 6 months | 
| Percentage of Participants Surviving at 12 Months (Phase 2) | Defined as the percentage of participants still alive from date of surgical resection until death or censored at 12 months | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, recurrent adult brain tumor