HSPPC-96 Vaccine With Temozolomide in Patients With Newly Diagnosed GBM

NCT00905060 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 081010C-100-37NCI-2015-01229
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 9

Brief Summary

This phase II trial studies the side effects and how well HSPPC-96 (vitespen) and temozolomide work in treating patients with newly diagnosed glioblastoma multiforme. Vaccines made from a person's tumor cells and heat shock protein peptide may help the body to build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving HSPPC-96 (vitespen) together with temozolomide may kill more tumor cells.

Conditions

Brain and Central Nervous System Tumors

Keywords

Newly Diagnosed Glioblastoma Multiforme, vaccine

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Related Adverse Events of Any Grade

  Up to 3 years

• Median Overall Survival

  Overall survival is defined as the time from surgical resection to death of any cause.

  Up to 3 years

Secondary Outcomes (2)

• Median Progression Free Survival (PFS)

  Up to 3 years

• Median PD-L1 Positivity in Circulating Myeloid Cells

  Up to 53 Weeks

Study Arms (1)

Protein Peptide-Complex (HSPPC-96)

EXPERIMENTAL

Patients will receive 4 weekly injections of HSPPC-96 followed by a 5th vaccine injection on the same day of the start of maintenance temozolomide administered 2 weeks (+ 4 days) following vaccine administration #4 on the same day of the start of maintenance temozolomide (Day 36). Monthly vaccine injections will then begin on day 21 (+/- 7 days) of the first 28 day temozolomide cycle (Day 56 of the study), 3 weeks following vaccine administration #5 and will continue every 28 days until depletion of vaccine or progression.

Biological: HSPPC-96; Drug: Temozolomide; Procedure: Standard Surgical Resection

Interventions

HSPPC-96 BIOLOGICAL

Autologous tumor-derived heat shock protein peptide-complex (HSPPC-96) administered at 25 μg per dose injected intradermally once weekly for 4 consecutive weeks and monthly following standard treatment with radiation and temozolomide.

Also known as: Heat Shock, Vitespen

Protein Peptide-Complex (HSPPC-96)

Temozolomide DRUG

Maintenance temozolomide treatment is given 2 weeks after administration of the fourth vaccine at an initial dose of 150 mg per square meter (mg/m2) for 5 consecutive days in a 28-day cycle. The dose was increased to 200 mg/m2 for 5 days in subsequent cycles.

Also known as: Temodar

Protein Peptide-Complex (HSPPC-96)

Standard Surgical Resection PROCEDURE

Patients will undergo standard surgical resection of intracranial tumor

Also known as: Craniotomy

Protein Peptide-Complex (HSPPC-96)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> or equal to 18 years old
• Life expectancy of greater than 12 weeks.
• Able to read and understand the informed consent document; must sign the informed consent
• Must have suspected diagnosis of Glioblastoma Multiforme with a surgical intent to resect at least 90% of enhancing disease
• Must be eligible for post-surgical treatment with radiotherapy and temozolomide
• Agree to use contraception or abstain from sexual activity from the time of consent through 1 month after the end of study drug administration
• Negative serum pregnancy test for female patients of childbearing potential
• Patients with histologically proven, non-progressive glioblastoma multiforme (GBM)
• Patient must have received standard of care radiation and temozolomide therapy
• Must have undergone a at least a 90% resection (determined by the principal investigator (PI)) measured by postoperative magnetic resonance imaging (MRI) scan, T1-weighted contrast scan, or CT scan if clinically indicated, performed within 72 hours after surgery
• All radiotherapy must be discontinued at least 2 weeks and no more than 5 weeks prior to the first planned vaccine administration
• Availability of at least 4 doses of vaccine (at least 4 vials for clinical administration produced from the tumor provided)
• Karnofsky functional status rating \> or equal to 70
• Adequate bone marrow function including the absence of lymphopenia (ANC \> 1,500/ mm3; absolute lymphocyte count (ALC) \> 500/mm3 ; platelet count \>100,000/mm3), adequate liver function (serum glutamic oxaloacetic transaminase/ aspartate aminotransferase (AST), alanine amino transferase (ALT), and alkaline phosphatase \<2.5 times institutional upper limit of normals \[IULNs\] and bilirubin (total) \<1.5 mg\*IULN), and adequate renal function (BUN and creatinine \<1.5 times IULNs

You may not qualify if:

• Pre-surgery tissue acquisition
• Current diagnosis of Human Immunodeficiency Virus (HIV testing is not required per protocol)
• Any prior diagnosis of any other cancer or other concurrent malignancy, with the exception of adequately treated nonmetastatic in situ carcinoma of the uterine cervix or nonmetastatic nonmelanoma skin cancer unless in complete remission and off all therapy for that disease for a minimum of 5 years
• Any systemic autoimmune disease (e.g., Hashimoto's thyroiditis) and/or any history of primary or secondary immunodeficiency
• Any prior therapy for glioma
• Planned use or current use of other investigational therapy for the treatment of glioma
• Inability to comply with study-related procedures
• Prior diagnosis of any other cancer or other concurrent malignancy, with the exception of adequately treated nonmetastatic in situ carcinoma of the uterine cervix or nonmetastatic nonmelanoma skin cancer unless in complete remission and off all therapy for that disease for a minimum of 5 years
• Current or active use of chemotherapy (except temozolomide) or immune therapy
• Contrast MRI findings (or CT scan if MRI is clinically contraindicated) consistent with progression per protocol defined modified Response assessment in neuro-oncology criteria (RANO) criteria. Progression prior to vaccination as determined by the Principal Investigator
• Patients with active uncontrolled infection
• Evidence of bleeding diathesis
• Unstable or severe intercurrent medical conditions
• Female patients who are pregnant or breastfeeding

Sponsors & Collaborators

• University of California, San Francisco: lead
• Agenus Inc.: collaborator

Study Sites (9)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

The Valley Hospital

Paramus, New Jersey, 07652, United States

Location

Northern Westchester Hospital

Mount Kisco, New York, 10549, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Bloch O, Lim M, Sughrue ME, Komotar RJ, Abrahams JM, O'Rourke DM, D'Ambrosio A, Bruce JN, Parsa AT. Autologous Heat Shock Protein Peptide Vaccination for Newly Diagnosed Glioblastoma: Impact of Peripheral PD-L1 Expression on Response to Therapy. Clin Cancer Res. 2017 Jul 15;23(14):3575-3584. doi: 10.1158/1078-0432.CCR-16-1369. Epub 2017 Feb 13.

  PMID: 28193626 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

vitespin; Heat-Shock Response; Temozolomide; Craniotomy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Stress, Physiological; Physiological Phenomena; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Neurosurgical Procedures; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Orin Bloch, MD
• Organization: University of California, Davis

obloch@ucdavis.edu

Study Officials

• Jennifer Clarke, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 18, 2009
• First Posted: May 20, 2009
• Study Start: June 29, 2009
• Primary Completion: June 3, 2014
• Study Completion: June 3, 2014
• Last Updated: March 24, 2021
• Results First Posted: March 24, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)