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

University of California San Francisco (UCSF)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Brain and Central Nervous System Tumors

Treatments: Biological: HSPPC-96; Procedure: Standard Surgical Resection

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00293423

R01CA164714-02 (U.S. NIH Grant/Contract)

NCI-2011-01231 (Registry Identifier)

P50CA097257-06 (U.S. NIH Grant/Contract)

05103

UCSF-H41995-27311-01 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 96 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

96 participants in 2 patient groups

Phase 1: Vaccine

Experimental group

Description:

Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections.

Treatment:

Procedure: Standard Surgical Resection

Biological: HSPPC-96

Phase 2: Vaccine

Experimental group

Description:

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.

Treatment:

Procedure: Standard Surgical Resection

Biological: HSPPC-96