PHASE 2, Multi-center, Single Arm Investigation of HSPPC-96 Vaccine With Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 9
- 主要终点
- Median Overall Survival
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Protein Peptide-Complex (HSPPC-96)
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.
干预措施: HSPPC-96 (Biological)
Protein Peptide-Complex (HSPPC-96)
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.
干预措施: Temozolomide (Drug)
Protein Peptide-Complex (HSPPC-96)
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.
干预措施: Standard Surgical Resection (Procedure)
结局指标
主要结局
Median Overall Survival
时间窗: Up to 3 years
Overall survival is defined as the time from surgical resection to death of any cause.
Number of Participants With Treatment-Related Adverse Events of Any Grade
时间窗: Up to 3 years
次要结局
- Median PD-L1 Positivity in Circulating Myeloid Cells(Up to 53 Weeks)
- Median Progression Free Survival (PFS)(Up to 3 years)
研究者
Orin Bloch, MD
Principal Investigator
University of California, San Francisco