Phase I/II Study of PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort)
研究概览
简要总结
Background:
The immune system is the cells and organs in the body that recognize and fight infection and cancer. The prostate specific antigen (PSA)/TRICOM (PROSTVAC) vaccine might teach the immune system to find and kill certain prostate cancer cells. Nivolumab is a drug that allows the immune system to fight tumors. It might help PROSTVAC work better.
Objective:
To test the safety and effectiveness of the combination of PROSTVAC and nivolumab. To test this for people with castration resistant prostate cancer and then for other people with localized prostate cancer who are candidates for surgical removal of the prostate.
Eligibility:
Men ages 18 and older with prostate cancer
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Electrocardiogram
Bone scan
Computed tomography (CT) scan or magnetic resonance imaging (MRI)
Tumor sample. This may be from a previous procedure.
All participants will get a combination of the study drugs over 8 weeks. They will have 1 visit for the initial injection then 3 booster injection / nivolumab infusion visits. Blood will be tested at these visits.
Over the next 4 weeks, some participants will have:
An exam of the large intestine through the rectum.
CT and bone scans
Standard hormonal treatment
Option to continue treatment every 3 weeks if their disease does not get worse. They will have scans every 12 weeks.
Other participants will have surgery to remove the prostate in week 9.
Participants will have a safety visit about a month after their last treatment. This will include a physical exam, blood tests, and possibly scans.
If their cancer progresses, participants will leave the study and may enroll in a long-term follow-up study. They will be contacted once a year to ask about their cancer and treatment.
详细描述
Background:
Immune checkpoint inhibitors interfere with the immune systems autoregulatory mechanisms, allowing for a potentially expanded and prolonged T-cell response with the possibility of greater antitumor effects.
Nivolumab is a fully human Immunoglobulin G4 (IgG4) monoclonal antibody that targets the programmed cell death protein 1 (PD-1) protein. Specifically, the antibody binds to the PD-1 receptor and blocks its interaction with programmed death-ligand 1 (PD-L1) and programmed cell death 1 ligand 2 (PD-L2), thereby releasing PD-1 pathway-mediated inhibition of the immune response, including anti-tumor immune response.
PROSTVAC (developed by the National Cancer Institute [NCI] and licensed to Bavarian Nordic Immunotherapeutics, Mountain View, California (CA) is a therapeutic cancer vaccine for prostate cancer. Early studies have demonstrated immunologic efficacy and suggested clinical benefit. A phase III trial has completed accrual.
A previous study combining the immune checkpoint inhibitor ipilimumab and PROSTVAC suggested greater efficacy than PROSTVAC alone. Additional studies have demonstrated the potential efficacy of immunologic combination therapy with the immune checkpoint inhibitor nivolumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 120 Years（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
Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort
Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year.
干预措施: PROSTVAC-V/F (Biological)
Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort
Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year.
干预措施: Nivolumab (Drug)
Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort
Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year.
干预措施: Tylenol (Drug)
Neoadjuvant Cohort
Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9.
干预措施: PROSTVAC-V/F (Biological)
Neoadjuvant Cohort
Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9.
干预措施: Nivolumab (Drug)
Neoadjuvant Cohort
Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9.
干预措施: Prostatectomy (Procedure)
Neoadjuvant Cohort
Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9.
干预措施: Biopsy (Procedure)
Neoadjuvant Cohort
Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9.
干预措施: Tylenol (Drug)
结局指标
主要结局
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort)
时间窗: From treatment start throughout study completion, an average of 1.4 years.
Clinically important immune-related adverse events were defined as grade 3 or above inflammation requiring steroids or anti cytokine therapy or not resolving to grade 1 or less within 28 days. These immune-related adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort)
时间窗: From baseline to radical prostatectomy (approximately week 9)
Changes in T-cell infiltration in the tumor after neoadjuvant treatment with PROSTVAC and nivolumab, is defined as difference in density of cytotoxic T lymphocytes (CD8 T) cells and clusters of differentiation 4 (CD4 T) cells infiltrate from baseline to post-treatment (radical prostatectomy performed at week 9), calculated utilizing computer automated staining analysis. The analysis was done per tissue compartment (normal region, intra-tumoral and invasive margin). We hypothesized an increase in T cell infiltration after treatment. Statistically significant changes in T-cell infiltration are those with p\<0.05; to 0.05. The changes are not statistically significant.
次要结局
- Changes in Magnetic Resonance Imaging (MRI) Secondary to Immune Treatment (Only for Neoadjuvant Cohort)(From baseline to closest date to prostatectomy, average on week 9.)
- Number of Participants With Peripheral Prostate-Specific Antigen (PSA)-Specific T Secondary To Immune Treatment(Weeks 7-10 and 17-22 compared to baseline)
- Number of Participants With Clinically Important Immune-related Adverse Events (Only for Neoadjuvant Cohort)(From baseline throughout study completion, an average of 20 weeks.)
- Changes in Soluble Immune Mediating Factors (Soluble Cluster of Differentiation 27 (sCD27) in Sera(Week 4, week 10, and week 20 after therapy compared to baseline)
- Changes in Soluble Immune Mediating Factors (Tumor Necrosis Factor Alpha (TNFα) and Interleukin 10 (IL-10) in Sera(Week 4, week 10, and week 20 after therapy compared to baseline)
- Changes in Immune Cell Subsets in the Peripheral Blood(Week 4 and week 10 after therapy compared to baseline.)
- Changes in Circulating Tumor Cells (CTCs) Levels(At baseline and at week 9)
- Number of Participants With a Pathologic Complete Response (pCR) (Only for Neoadjuvant Cohort)(From baseline and time of radical prostatectomy (average of week 9))
- Rate of Biochemical Recurrence After Prostatectomy (Only for Neoadjuvant Cohort)(From time of prostatectomy through study completion, an average of 10 weeks)
- Best Overall Response for Participants With Measurable Disease (Only in the Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort)(Baseline throughout study completion (average 1.4 years))
- Percent Change of Tumor Cells Expressing Programmed Death-ligand 1 (PDL-1) (for the Neo-adjuvant Cohort)(Baseline (biopsy before first PROSTVAC administration) and at time of radical prostatectomy (on week 9))
- Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4+) and Forkhead Box P3 (FOX-P3) Staining (Only for Neoadjuvant Cohort)(Baseline and at time of prostatectomy (approximately week 9))
- Number of Participants With Serologic Response(From baseline throughout study completion, an average of 1.4 years.)
- Changes in Apparent Diffusion Coefficient (ADC) Mapping, Secondary to Immune Treatment (Only for Neoadjuvant Cohort)(From baseline to closest date to prostatectomy, average on week 9.)
研究者
James Gulley, M.D.
Principal Investigator
National Cancer Institute (NCI)