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

NCT ID: NCT00293423

Last Updated: 2021-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-18
• Study Completion Date: 2013-01-12

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1: Vaccine

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

Group Type: EXPERIMENTAL

HSPPC-96

Intervention Type: BIOLOGICAL

25 mcg

Standard Surgical Resection

Intervention Type: PROCEDURE

Patients will undergo standard surgical resection of intracranial tumor

Phase 2: Vaccine

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.

Group Type: EXPERIMENTAL

HSPPC-96

Intervention Type: BIOLOGICAL

25 mcg

Standard Surgical Resection

Intervention Type: PROCEDURE

Patients will undergo standard surgical resection of intracranial tumor

Interventions

HSPPC-96

25 mcg

Intervention Type: BIOLOGICAL

Standard Surgical Resection

Patients will undergo standard surgical resection of intracranial tumor

Intervention Type: PROCEDURE

Other Intervention Names

Heat Shock; Glycoprotein 96; Gp96; Craniotomy

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Agenus Inc.

INDUSTRY

Sponsor Role: collaborator

American Brain Tumor Association

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Orin Bloch, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer Clarke, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

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

Countries

United States

References

Crane CA, Han SJ, Ahn B, Oehlke J, Kivett V, Fedoroff A, Butowski N, Chang SM, Clarke J, Berger MS, McDermott MW, Prados MD, Parsa AT. Individual patient-specific immunity against high-grade glioma after vaccination with autologous tumor derived peptides bound to the 96 KD chaperone protein. Clin Cancer Res. 2013 Jan 1;19(1):205-14. doi: 10.1158/1078-0432.CCR-11-3358. Epub 2012 Aug 7.

Reference Type: BACKGROUND

PMID: 22872572 (View on PubMed)

Bloch O, Crane CA, Fuks Y, Kaur R, Aghi MK, Berger MS, Butowski NA, Chang SM, Clarke JL, McDermott MW, Prados MD, Sloan AE, Bruce JN, Parsa AT. Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial. Neuro Oncol. 2014 Jan;16(2):274-9. doi: 10.1093/neuonc/not203. Epub 2013 Dec 12.

Reference Type: RESULT

PMID: 24335700 (View on PubMed)

Other Identifiers

UCSF-H41995-27311-01

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2011-01231

Identifier Type: REGISTRY

Identifier Source: secondary_id

P50CA097257-06

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01CA164714-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

05103

Identifier Type: -

Identifier Source: org_study_id