Clinical trial NCT00905060: HSPPC-96 Vaccine With Temozolomide in Patients With Newly Diagnosed GBM
Official title: PHASE 2, Multi-center, Single Arm Investigation of HSPPC-96 Vaccine With Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: Newly Diagnosed Glioblastoma Multiforme, vaccine
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Agenus Inc.
First posted: 2009-05-20
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: PRIMARY OBJECTIVES:

I. To evaluate the safety profile of HSPPC-96 (vitespen) administered concurrently with temozolomide in patients with newly diagnosed glioblastoma multiforme (GBM).

II. To evaluate survival in patients treated with an autologous tumor-derived heat shock protein peptide-complex (HSPPC-96) with concurrent temozolomide.

SECONDARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) from date of surgical resection. II. To evaluate the immunologic response to vaccine treatment in a subset of evaluable patients.

OUTLINE:

Approximately 2-5 weeks after standard radiation therapy and temozolomide completion, patients receive vitespen intradermally (ID) on days 1, 8, 15, and 22. Beginning 2 weeks after the 4th dose of vitespen, patients receive a 5th dose of vitespen ID and maintenance temozolomide orally (PO) on days 1-5 (of 28 day courses). On day 21 of course 1, patients receive the 6th dose of vitespen ID and continue vaccinations monthly. Courses repeat every 28 days in the absence of vaccine depletion, disease progression, or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks.

Eligibility criteria: Inclusion Criteria:

Pre-surgery tissue acquisition Inclusion criteria

1. Age \> or equal to 18 years old
2. Life expectancy of greater than 12 weeks.
3. Able to read and understand the informed consent document; must sign the informed consent
4. Must have suspected diagnosis of Glioblastoma Multiforme with a surgical intent to resect at least 90% of enhancing disease
5. Must be eligible for post-surgical treatment with radiotherapy and temozolomide

Post-radiation therapy/pre-vaccine eligibility Inclusion criteria

1. Agree to use contraception or abstain from sexual activity from the time of consent through 1 month after the end of study drug administration
2. Negative serum pregnancy test for female patients of childbearing potential
3. Patients with histologically proven, non-progressive glioblastoma multiforme (GBM)
4. Patient must have received standard of care radiation and temozolomide therapy
5. 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
6. All radiotherapy must be discontinued at least 2 weeks and no more than 5 weeks prior to the first planned vaccine administration
7. Availability of at least 4 doses of vaccine (at least 4 vials for clinical administration produced from the tumor provided)
8. Karnofsky functional status rating \> or equal to 70
9. 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

Exclusion Criteria:

Pre-surgery tissue acquisition

1. Current diagnosis of Human Immunodeficiency Virus (HIV testing is not required per protocol)
2. 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
3. Any systemic autoimmune disease (e.g., Hashimoto's thyroiditis) and/or any history of primary or secondary immunodeficiency
4. Any prior therapy for glioma
5. Planned use or current use of other investigational therapy for the treatment of glioma

Post-radiation therapy/pre-vaccine Exclusion

1. Inability to comply with study-related procedures
2. 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
3. Current or active use of chemotherapy (except temozolomide) or immune therapy
4. 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
5. Patients with active uncontrolled infection
6. Evidence of bleeding diathesis
7. Unstable or severe intercurrent medical conditions
8. Female patients who are pregnant or breastfeeding

Primary outcomes:
measure: Number of Participants With Treatment-Related Adverse Events of Any Grade
timeFrame: Up to 3 years
measure: Median Overall Survival
timeFrame: Up to 3 years
Secondary outcomes:
measure: Median Progression Free Survival (PFS)
timeFrame: Up to 3 years
measure: Median PD-L1 Positivity in Circulating Myeloid Cells
timeFrame: Up to 53 Weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Paramus
country: United States
facility: The Valley Hospital
state: New Jersey
city: Mount Kisco
country: United States
facility: Northern Westchester Hospital
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of California, San Francisco
name: Jennifer Clarke, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.