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

University of California, San Francisco96 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Brain and Central Nervous System Tumors

Interventions

HSPPC-96BIOLOGICAL

25 mcg

Standard Surgical ResectionPROCEDURE

Patients will undergo standard surgical resection of intracranial tumor

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

University of California, San Francisco

San Francisco, California, United States

Columbia University

New York, New York, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Outcomes

Primary Outcomes

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

Time frame: 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.

Time frame: 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

Time frame: Up to 4 weeks

Median Progression-free Survival at 6 Months (Phase 2)

Time frame: 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

Time frame: Up to 12 months

Secondary Outcomes

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

Data from ClinicalTrials.gov

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