A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC/TRICOM and Flutamide vs. Flutamide Alone in Men With Androgen Insensitive, Non-Metastatic (D0.5) Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 3
- 主要终点
- Time to Treatment Failure
研究概览
简要总结
Background:
- Flutamide is an approved drug for prostate cancer that blocks the effects of testosterone on prostate cancer cells and may slow the progression of the disease.
- The vaccine in this study consists of a priming vaccine called PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM (triad of costimulatory molecules), made from vaccinia virus, and a boosting vaccine called PROSTVAC-F/TRICOM, made from fowlpox virus. DNA (Deoxyribonuceic acid) is inserted into the priming and boosting vaccine viruses to cause production of proteins that enhance immune activity and also to produce prostate specific antigen (PSA) a protein that is normally produced by the patients tumor cells.
- GM-CSF (granulocyte macrophage colony stimulating factor), given along with the vaccine, is a chemical that boosts the immune system. It is used in this study to try to increase the usefulness of the vaccine by increasing the number of immune cells at the vaccination site.
Objectives:
-To determine if treatment with a prostate cancer vaccine plus flutamide is more effective than flutamide alone in delaying disease progression in patients with prostate cancer.
Eligibility:
- Patients 18 years of age and older with androgen-insensitive prostate cancer that has not spread beyond the prostate gland.
- Patients with a rising PSA (prostatic specific antigen) who have already been treated with anti-iandrogen therapy (either bicalutamide or nilutamide).
Design:
- There are two treatment groups in this study. Group A receives only flutamide; group B receive flutamide plus vaccine.
- Patients in both groups receive flutamide by mouth three times a day.
- Patients in group B receive PROSTVAC-V/TRICOM on day 1 and PROSTVAC-F/TRICOM on day 29 and again every 4 weeks. All vaccines are given as injections under the skin.
- Patients have blood tests for PSA levels every month and scans every 3 months until the disease worsens.
- After 3 months of therapy, patients receiving in group A (flutamide alone) may cross over to receive vaccine if they develop a rising PSA and scans show no sign of disease spread. Patients in group B (flutamide plus vaccine) stop flutamide and may continue vaccine therapy. At this point patients may continue to receive treatment until the disease progresses or PSA levels rise....
详细描述
Background:
- There is no standard of care for prostate cancer patients progressing on hormone therapy with a rising serum PSA (prostatic specific antigen) level without evidence of metastatic disease.
- We have completed a phase II trial in which men with this stage of disease were randomized to receive a pox vector PSA vaccine vs. the antiandrogen nilutamide.
- The median time to treatment failure on nilutamide was 7.6 months.
- 12 patients on the vaccine arm had nilutamide added at the time of PSA progression.
- The median time for treatment failure after the addition of nilutamide was 13.9 months, for a total of 25.9 months from initiation of vaccine therapy.
- This suggests that the combination of hormone therapy with vaccine therapy may lead to an improved clinical benefit compared to hormone therapy alone.
- Due to the increased toxicity of nilutamide compared to other antiandrogens and the patients prior exposure to bicalutamide therapy, we plan to use flutamide as a second line hormonal manipulation in the below study.
Objectives (Primary):
-To determine if use of a combination of vaccine plus flutamide may be associated with a trend toward improvement in time to treatment failure compared to flutamide alone.
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 110 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
Flutamide Alone
Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued.
干预措施: Flutamide (Eulexin) (Drug)
Flutamide + Vaccine + Sargramostim
Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.
干预措施: Sargramostim (GM-CSF, Leukine) (Drug)
Flutamide + Vaccine + Sargramostim
Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.
干预措施: Flutamide (Eulexin) (Drug)
Flutamide + Vaccine + Sargramostim
Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.
干预措施: PROSTVAC-F/ TRICOM (Biological)
Flutamide + Vaccine + Sargramostim
Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.
干预措施: PROSTVAC-V/TRICOM (Biological)
结局指标
主要结局
Time to Treatment Failure
时间窗: Median Potential Follow-up of 46.7 months
Time to treatment failure is defined as a rising Prostatic Specific Antigen (PSA) (Bubley criteria, JCO 1999), development of metastatic disease, or removal from treatment due to excessive toxicity) compared to patients receiving flutamide alone. Normal PSA is 4.0 ng/mL or lower.
次要结局
- Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)(Median Potential Follow-up of 46.7 months)
- Number of Participants With Prostatic Specific Antigen (PSA) Response(Median potential follow-up for all patients is 46.7 months)
- Percentage of Participants With Antigen Specific Immune Responses Against Prostatic Specific Antigen (PSA)(3 months)
研究者
Ravi A. Madan, M.D.
Principal Investigator
National Cancer Institute (NCI)