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

Study Overview
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Brief Summary
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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
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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.

Official Title
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PHASE 2, Multi-center, Single Arm Investigation of HSPPC-96 Vaccine With Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: HSPPC-96
* Drug: Temozolomide
* Procedure: Standard Surgical Resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-surgery tissue acquisition Inclusion criteria 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 Post-radiation therapy/pre-vaccine eligibility Inclusion criteria 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 Exclusion Criteria: 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 Post-radiation therapy/pre-vaccine Exclusion 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Protein Peptide-Complex (HSPPC-96)<br>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<br>* 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.<br>* Other names: Vitespen;Drug: Temozolomide<br>* 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.<br>* Other names: Temodar;Procedure: Standard Surgical Resection<br>* Patients will undergo standard surgical resection of intracranial tumor<br>* Other names: Craniotomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression Free Survival (PFS) | PFS is defined as the duration of progression-free survival from the time from resection until either documented disease progression or death | Up to 3 years | 
| Median PD-L1 Positivity in Circulating Myeloid Cells | Circulating myeloid cells (CD45+/CD11b+) obtained from patients at the time of surgery were analyzed for PD-L1 expression to determine the percent of myeloid cells positive for PD-L1 (cut off for positivity determined relative to Fluorescence Minus One (FMO) and isotype control). | Up to 53 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Newly Diagnosed Glioblastoma Multiforme, vaccine