Clinical trial NCT00293423: GP96 Heat Shock Protein-Peptide Complex Vaccine in Treating Patients With Recurrent or Progressive Glioma
Official title: Phase I/II Trial of Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine for Patients With Recurrent High Grade Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma
recurrent adult brain tumor
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Agenus Inc.
name: American Brain Tumor Association
First posted: 2006-02-17
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) (Phase 1)
timeFrame: Up to 4 weeks
measure: Frequency of gp96 Heat Shock Protein-peptide Complex Vaccine (Phase 1)
timeFrame: Up to 6 months
measure: Number of Participants With Dose Limiting Toxicities (Phase 1)
timeFrame: Up to 4 weeks
measure: Median Progression-free Survival at 6 Months (Phase 2)
timeFrame: 6 months
measure: Percentage of Participants With Progression-free Survival at 12 Months (Phase 2)
timeFrame: Up to 12 months
Secondary outcomes:
measure: Number of Patients With an Immunological Response (Phase 1)
timeFrame: Up to 12 months
measure: Number of Patients With an Immunological Response (Phase 2)
timeFrame: Up to 2 years
measure: Number of Participants With Grade 3 or Higher, Vaccine Treatment-Related Adverse Events by Toxicity (Phase 2)
timeFrame: Up to 2 years
measure: Median Overall Survival (Phase 2)
timeFrame: Up to 2 years
measure: Percentage of Participants Surviving at 6 Months (Phase 2)
timeFrame: Up to 6 months
measure: Percentage of Participants Surviving at 12 Months (Phase 2)
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New York
country: United States
facility: Columbia University
state: New York
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
Study officials:
affiliation: University of California, San Francisco
name: Jennifer Clarke, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.