A Phase II Study of CTLA Blockade by Ipilimumab Plus Androgen Suppression Therapy in Patients With an Incomplete Response to AST Alone for Metastatic Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 4
- 主要终点
- Percentage of Patients Who Achieve an Undetectable PSA (=< 0.2 ng/ml)
研究概览
简要总结
This phase II trial studies how well ipilimumab works when given together with androgen suppression therapy in treating patients with hormone-resistant prostate cancer that has spread to other parts of the body. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Androgen can cause the growth of prostate cancer. Androgen deprivation therapy may stop the adrenal glands from making androgen. Giving ipilimumab together with androgen suppression therapy may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Proportion of patients who achieve an undetectable prostate-specific antigen (PSA) (=< 0.2 ng/ml) after initiation of ipilimumab therapy.
SECONDARY OBJECTIVES:
I. Time to PSA progression. II. Time to progression by any measure. III. Maximum percentage of PSA reduction in each patient. IV. Number of patients with immune related adverse events (IRAEs) and correlation of these with complete PSA response, time to progression, and T cell measurements.
V. Measures of T cell response to therapy with flow cytometry. VI. Response in measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Willing and able to give written informed consent
- •Histologic diagnosis of adenocarcinoma of the prostate
- •A PSA of > 0.2 ng/ml after 6-18 months of androgen suppression therapy, which may consist of luteinizing hormone-releasing hormone (LHRH) agonist or antagonist alone or the combination of an LHRH agonist or antagonist plus an antiandrogen, such as bicalutamide; androgen suppression therapy will continue without interruption
- •Radiographic evidence of regional or distant metastasis at the time of study enrollment or at the time of diagnosis
- •White blood cell (WBC) >= 2000/uL
- •Absolute neutrophil count (ANC) >= 1000/uL
- •Platelets >= 50 x 10^3/uL
- •Hemoglobin >= 8 g/dL
- •Creatinine =< 3.0 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN for patients without liver metastasis
- •Bilirubin =< 3.0 x ULN, (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL)
- •No known active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; patients should be assessed for high risk behaviors that may result in these infections, such as intravenous drug use or multiple sexual partners; the assessment should be noted
- •Eastern Cooperative Oncology Group (ECOG) =< 1
- •Patients receiving any herbal product known to decrease PSA levels (i.e. saw palmetto and prostate cancer [PC]-SPES), or any immunosuppressive dose of systemic or absorbable topical corticosteroid (except prednisone up to 10 mg orally per [q] day, or its equivalent), must discontinue the agent for at least 2 weeks prior to screening; progressive disease must be documented after discontinuation of these products
- •Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks with stable symptoms prior to the first infusion with ipilimumab
- •Total testosterone < 50 ng/ml, except in patients with prior orchiectomy, where testosterone does not need to be measured; patients must continue their LHRH agonist therapy throughout study duration
- •Life expectancy >= 6 months; this must be documented
- •Patients who are sexually active with a partner who could become pregnant are to use an effective form of barrier contraception, such as condoms or a partner using oral contraceptive pills; persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 weeks after ipilimumab is stopped
- •If a patient enters the trial on androgen suppression therapy (AST) that consists of both an LHRH agonist and an oral antiandrogen, both agents should be continued throughout the study; if an antiandrogen is stopped prior to study entry, it should be stopped 4 weeks before for nilutamide and flutamide and 6 weeks before for bicalutamide to ensure that a withdrawal phenomenon does not interfere with interpretation of efficacy results
排除标准
- •Radiation to any area of the body < 28 days prior to randomization
- •Any other active malignancy with the exception of adequately treated basal or squamous cell skin cancer or superficial bladder cancer
- •Autoimmune disease: patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. myasthenia gravis, Guillain-Barre syndrome); those with immune-mediated skin toxicity (i.e. toxic epidermal necrolysis, Stevens-Johnson syndrome) will also be excluded
- •Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
- •Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab)
- •A history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or agonist
- •Concomitant therapy with any of the following: interleukin (IL)-2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents (over the counter [OTC]/herbal/prescribed); immunostimulant agents, other than the study agent; other investigational therapies; or chronic use of systemic corticosteroids (greater than prednisone 10 mg orally per day, or its equivalent)
- •Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (i.e., infectious) illness
结局指标
主要结局
Percentage of Patients Who Achieve an Undetectable PSA (=< 0.2 ng/ml)
时间窗: Up to 5 years
Undetectable PSA (prostate-specific antigen) defined as PSA ≤ 0.2 ng/mg after initiation of ipilimumab therapy. Provided with the exact 95% confidence interval. PSA response as recommended by the Prostate Cancer Clinical Trials Working Group (PCWG2) definitions. Percentage can take on values between 0% and 100%.
次要结局
- Time to Death From Any Cause(Up to 5 years)
- Correlation Between IRAE and PSA Progression.(Up to 5 years)
- Correlation of IRAEs With Ratio of T Regulatory Cells to T Effector Cells(Up to day 1 of course 4)
- Correlation Between IRAEs and Immune Response(Up to day 1 of course 4)
- Correlation Between IRAE and Any Progression.(Up to 5 years)
- Time to PSA Progression(Up to 5 years)
- Time to Progression by Any Measure(Up to 5 years)
- Number of Patients With IRAEs(Up to 6 months)
- Correlation Between IRAE and Radiographic Progression.(Up to 5 years)
- Correlation Between IRAE and Overall Survival.(Up to 5 years)
研究者
Julie Graff
Principal Investigator
OHSU Knight Cancer Institute