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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00293423
• Other study ID #: 05103
• Secondary ID: UCSF-H41995-2731
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 18, 2005
• Est. completion date: January 12, 2013

Study information

• Verified date: May 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: January 12, 2013
• Est. primary completion date: January 12, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Biological:
• HSPPC-96
25 mcg

Procedure:
• Standard Surgical Resection
Patients will undergo standard surgical resection of intracranial tumor

Locations

Country	Name	City	State
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Columbia University	New York	New York
United States	University of California, San Francisco	San Francisco	California

Sponsors (4)

Lead Sponsor	Collaborator
University of California, San Francisco	Agenus Inc., American Brain Tumor Association, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. Neu — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Median Progression-free Survival at 6 Months (Phase 2)		6 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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