A Pilot Study to Test the Feasibility and Immunologic Impact of Sipuleucel-T (Provenge) Administered With or Without Anti-PD-1 mAb (CT-011) and Low Dose Cyclophosphamide in Men With Advanced Castrate-Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Determine Feasibility of Provenge Plus Low-dose Cyclophosphamide as Well as the Immune Efficacy of Provenge Alone Versus Provenge Plus Low-dose Cyclophosphamide and Anti PD1 Monoclonal Antibodies (CT011) on the Change in Specific Immune Response.
研究概览
简要总结
Background:
- Sipuleucel-T is a new treatment for advanced stage prostate cancer. It takes cells from a person with prostate cancer and treats them in the laboratory. Then it returns the cells to the person to help the immune system fight the cancer. Sipuleucel-T may be combined with the drug CT-011 to boost its ability to kill cancer cells. The chemotherapy drug cyclophosphamide will also be given, either before or after the cells are collected at the start of the treatment.
Objectives:
- To test the effectiveness of Sipuleucel-T, CT-011, and cyclophosphamide for prostate cancer.
Eligibility:
- Men at least 18 years of age who have advanced prostate cancer.
Design:
- Participants will be screened with a medical history, physical exam, blood and urine tests, and imaging studies.
- This study has two parts, with different participants in each part. All participants will be monitored with frequent blood tests and imaging studies.
- Part I:
- Participants will provide cells for the Sipuleucel-T treatment three times. The first time will be 3 days before the chemotherapy. The second time will be 10 days after chemotherapy. The third time will be 24 days after chemotherapy.
- Participants will have one dose of cyclophosphamide the day before the first dose of Sipuleucel-T.
- Participants will have Sipuleucel-T about 3 days after each cell donation.
- Part II:
- Participants will be in three groups: Sipuleucel-T given alone, given with CT-011, or given with both cyclophosphamide and CT-011.
- Participants will provide cells for the Sipuleucel-T treatment three times, as in Part I.
- Participants will have Sipuleucel-T about 3 days after each cell donation, and will receive treatment with the other drugs as directed by the study doctors.
详细描述
Background:
- Prostate cancer is the most common cancer and the second leading cause of cancer deaths among males in most Western countries.
- Sipuleucel-T, a recently FDA approved treatment for prostate cancer, is designed to induce an immune response targeted against PAP, an antigen expressed in most prostate cancers. .
- Blockade of PD-1/PD-L1 has been shown to enhance the therapeutic efficacy of peptide cancer vaccines in pre-clinical animal models. CT-011 is a humanized IgG1 kappa recombinant monoclonal antibody against PD-1 receptor that blocks the interaction of PD-L1 with PD-1.
- Preclinical studies demonstrated that CT-011 when administered with low dose cyclophosphamide led to synergistic antitumor effects when combined with HPV16 E749-57 peptide vaccine.
- Given the role CT-011 plays in down-regulating peripheral tolerance and the synergistic relationship it has with cyclophosphamide in doing so, in this study we propose to treat patients with advanced, castrate-resistant disease with CT-011 and low-dose cyclophosphamide as adjuvants in combination with Provenge(Trademark) activated cell vaccine.
Objectives:
- To assess the feasibility of administration of Sipuleucel-T (Provenge(Trademark)) autologous active cellular immunotherapy in combination with low dose cyclophosphamide in men with advanced castrate-resistant (hormone refractory) prostate cancer.
- To determine the immune efficacy of Sipuleucel-T (Provenge(Trademark)) autologous active cellular immunotherapy alone vs. Sipuleucel-T (Provenge(Trademark)) in combination with CT- 011 vs. Sipuleucel-T (Provenge(Trademark)) in combination with low-dose cyclophosphamide and CT-011 on the change in PA2024-specific IFN-? ELISPOT responses in men with advanced, castrate-resistant prostate cancer.
- Secondary objectives will determine the tolerability and toxicities of the combination of low-dose cyclophosphamide/CT-011/ Sipuleucel-T (Provenge(Trademark)) and determine in a preliminary fashion whether this regimen correlates with increased progression-free survival (PFS) and overall survival (OS) in patients and with growth rate in an exploratory fashion.
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A
Sipuleucel-T autologous active cellular immunotherapy only for 3 cycles (cycle = 14 days)
干预措施: Sipuleucel-T (Provenge) (Other)
Arm B
Sipuleucel-T for 3 cycles (cycle = 14 days) + CT-011 (3mg/kg) IV infusion delivered over approximately 2 hours, 2 days after each Sipuleucel-T infusion
干预措施: CT-011 (Anti-PD1 Antibody) (Drug)
Arm B
Sipuleucel-T for 3 cycles (cycle = 14 days) + CT-011 (3mg/kg) IV infusion delivered over approximately 2 hours, 2 days after each Sipuleucel-T infusion
干预措施: Sipuleucel-T (Provenge) (Other)
Arm C
Sipuleucel-T for 3 cycles (cycle = 14 days)+ cyclophosphamide (125 or 250mg/m2) IV [first cycle only] + CT-011 (3mg/kg) IV infusion delivered over approximately 2 hours, 2 days after each Sipuleucel-T infusion
干预措施: CT-011 (Anti-PD1 Antibody) (Drug)
Arm C
Sipuleucel-T for 3 cycles (cycle = 14 days)+ cyclophosphamide (125 or 250mg/m2) IV [first cycle only] + CT-011 (3mg/kg) IV infusion delivered over approximately 2 hours, 2 days after each Sipuleucel-T infusion
干预措施: Sipuleucel-T (Provenge) (Other)
Arm C
Sipuleucel-T for 3 cycles (cycle = 14 days)+ cyclophosphamide (125 or 250mg/m2) IV [first cycle only] + CT-011 (3mg/kg) IV infusion delivered over approximately 2 hours, 2 days after each Sipuleucel-T infusion
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Determine Feasibility of Provenge Plus Low-dose Cyclophosphamide as Well as the Immune Efficacy of Provenge Alone Versus Provenge Plus Low-dose Cyclophosphamide and Anti PD1 Monoclonal Antibodies (CT011) on the Change in Specific Immune Response.
时间窗: 2 years
次要结局
- Determine Whether the Combination of Low Dose-Cyclophosphamide and Anti PD1 Monoclonal Antibodies (CT-011) With Provenge(tm) Lead to Improvement in Increase Progression Free Survival (PFS) and Overall Survival (OS) in Patients With Advanced, Min...(2 years)
研究者
Samir N. Khleif
Cancer Center Director
Augusta University