CHAARTED: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 790
- 试验地点
- 343
- 主要终点
- Overall Survival
研究概览
简要总结
RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen ablation therapy may stop the adrenal glands from making androgens. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether androgen-ablation therapy is more effective with or without docetaxel in treating metastatic prostate cancer.
PURPOSE: This randomized phase III trial is studying androgen-ablation therapy and chemotherapy to see how well they work compared to androgen-ablation therapy alone in treating patients with metastatic prostate cancer.
详细描述
OBJECTIVES:
Primary
- Evaluate the ability of early chemotherapy to improve overall survival of patients commencing androgen deprivation for metastatic prostate cancer.
Secondary
- Determine whether early chemotherapy can increase the time to clinical progression (radiographic or symptomatic deterioration due to disease) over hormonal therapy alone.
- Determine whether early chemotherapy can increase the time to development of hormone-refractory disease over hormonal therapy alone.
- Determine whether early chemotherapy can increase the time to serological progression over hormonal therapy alone.
- Determine rates of biochemical response at 6 months and 12 months in the chemohormonal arm versus the hormonal therapy alone arm.
- Determine the frequency of adverse events and the tolerability of chemotherapy combined with hormonal therapy versus hormonal therapy alone.
- Determine whether the postulated clinically meaningful increase in disease control is associated with an alteration in overall quality of life using the Functional Assessment of Cancer Therapy-Prostate questionnaire.
- Determine the ability of prostate-specific antigen (PSA) changes to be a surrogate for clinical benefit from therapy and overall survival.
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
- •Histologically or cytologically confirmed prostate cancer
- •Metastatic disease
- •On androgen-deprivation therapy for < 120 days
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
- •PS 2 eligible only if decline in PS is due to metastatic prostate cancer
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin ≤ upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) ≤ 2.5 times ULN
- •Creatinine clearance ≥ 30 mL/min
- •Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 times ULN (unless on therapeutic anticoagulation)
- •Partial thromboplastin time (PTT) ≤ 1.5 times ULN (unless on therapeutic anticoagulation)
- •Fertile patients must use effective contraception
- •At least 4 weeks since prior major surgery and recovered from all toxicity prior to randomization
- •Prior adjuvant or neoadjuvant hormonal therapy allowed provided the following are true:
- •Therapy was discontinued ≥ 12 months ago AND there is no evidence of disease, as defined by 1 of the following:
- •PSA < 0.1 ng/dL after prostatectomy plus hormonal therapy
- •PSA < 0.5 ng/dL and has not doubled above nadir after radiotherapy plus hormonal therapy
- •Therapy lasted no more than 24 months
- •Last depot injection must have expired by the 24-month mark
- •Prior palliative radiotherapy allowed if commenced within 30 days before starting androgen deprivation
- •Anti-androgen therapy allowed as single-agent therapy ≤ 7 days before medial castration to prevent flare
- •More than 30 days (or 6 half-lives) (whichever is longer) since prior participation in another clinical trial
- •Concurrent participation in nontherapeutic trials allowed
- •Concurrent antiandrogen therapy (e.g., bicalutamide or flutamide) allowed, but not as sole hormonal therapy
排除标准
- •Prostate-specific antigen (PSA) level has risen and met criteria for progression from its lowest point between the start of androgen-deprivation therapy and randomization
- •Prior malignancy in the past 5 years except for basal cell or squamous cell carcinoma of the skin
- •Other malignancies that are considered to have low potential to progress (e.g., grade 2, T1a transitional cell carcinoma) may be allowed if approved by study chair
- •Peripheral neuropathy > grade 1
- •History of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
- •Active cardiac disease, including the following:
- •Active angina
- •Symptomatic congestive heart failure
- •Myocardial infarction within the past 6 months
- •Prior chemotherapy in adjuvant or neoadjuvant setting
- •Prior hormone therapy in the metastatic setting
- •Concurrent 5-alpha reductase inhibitors
- •Simultaneous enrollment on Cancer and Leukemia Group B (CALGB) 90202
研究组 & 干预措施
Androgen-Deprivation Therapy and Docetaxel
Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration). Patients also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: androgen-deprivation therapy (Drug)
Androgen-Deprivation Therapy and Docetaxel
Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration). Patients also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: docetaxel (Drug)
Androgen-Deprivation Therapy alone
Patients receive androgen-deprivation therapy (including luteinizing hormone-releasing hormone [LHRH] agonist therapy, LHRH antagonist therapy, or surgical castration) alone.
干预措施: androgen-deprivation therapy (Drug)
结局指标
主要结局
Overall Survival
时间窗: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry
Overall survival is defined as the time from randomization to death or date last known alive. Survival data reflects the database as of December 23, 2013.
次要结局
- Time to Clinical Progression(Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry)
- Time to Castration Resistant Prostate Cancer (Hormone Refractory Disease)(Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry)
- Proportion of Patients With PSA Complete Response (CR) at 6 Months(Assessed at 6 months)
- Proportion of Patients With PSA Complete Response (CR) at 12 Months(Assessed at 12 months)
- QOL Change From Baseline to 3 Months(Assessed at baseline and 3 months)