A Randomized Double-Blind Phase 3 Trial Comparing Docetaxel Combined With Dasatinib to Docetaxel Combined With Placebo in Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,930
- 试验地点
- 43
- 主要终点
- Overall Survival: Time From Randomization to Date of Death
研究概览
简要总结
The purpose of this study is to determine whether survival can be prolonged in patients with castration-resistant prostate cancer who receive dasatinib with docetaxel and prednisone.
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
- Double (Participant, Investigator)
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
- •History of histologically diagnosed prostate cancer
- •Evidence of metastatic disease by any 1 of the following: computed tomography scan, magnetic resonance imaging, bone scan, or skeletal survey
- •Evidence of progression, as defined by 1 of the following: rising prostate specific antigen levels at least 1 week apart with the final value being >=2 ng/mL; progression of measurable nodal or visceral disease, with nodal lesions >=20 mm and visceral lesions measurable per response evaluation criteria for solid tumors (Response Evaluation in Solid Tumors, version 1); 2 or more lesions appearing on bone scan compared with previous scan; or local recurrence in the prostate or prostate bed
- •Maintaining castrate status: Participants who have not undergone surgical orchiectomy should have received and continue on medical therapies, such as gonadotropin releasing hormone analogs, to maintain castrate levels of serum testosterone <=50 ng/dL
- •Eastern Cooperative Oncology Group Performance Status of 0 to 2
- •At least 4 weeks since an investigational agent prior to starting study therapy
- •At least 8 weeks since radioisotope therapy prior to starting study therapy
- •Recovery from any local therapy including surgery or radiation/radiotherapy for a minimum of 7 days prior to starting study therapy
- •Required initial laboratory values: white blood cell count >=3,000/mm^3; absolute neutrophil count >=1,500/mm^3; platelet count >=100,000/mm^3; creatinine level <=1.5*upper limit of normal (ULN); bilirubin <=ULN; aspartate aminotransferase <=2.5*ULN; alanine aminotransferase <=2.5*ULN.
排除标准
- •Symptomatic brain metastases or leptomeningeal metastases
- •Clinically significant cardiovascular disease, including myocardial infarction; ventricular tachyarrhythmia within 6 months; prolonged QTc >450 msec; ejection fraction <40%; or major conduction abnormality, unless a cardiac pacemaker is present
- •Pleural or pericardial effusion of any Common Terminology Criteria (CTC) grade
- •Peripheral neuropathy CTC Grade >=2
- •Currently active second malignancy other than nonmelanoma skin cancers. Participants are not considered to have a currently active malignancy if they have completed therapy and are now considered (by their physician) to be at less than 30% risk for relapse
- •Uncontrolled intercurrent illness including ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •HIV infection-positive patients receiving combination antiretroviral therapy
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to the investigational agents
- •Receipt of any other investigational agents for the treatment of prostate cancer
- •Prior cytotoxic chemotherapy in the metastatic setting, with the exception of estramustine
- •Patients may continue on a daily multivitamin but must discontinue all other herbal, alternative, and food supplements before enrollment
- •Ketoconazole must be discontinued 4 weeks prior to starting study therapy
- •Antiandrogens must be discontinued prior to starting study therapy. Patients with a history of response to an antiandrogen and subsequent progression while on that antiandrogen should be assessed for antiandrogen withdrawal response for 4 weeks. Observation for antiandrogen withdrawal response is not necessary for those who have never responded to antiandrogens
- •Bisphosphonates must not be initiated within 28 days prior to starting study therapy
- •QT prolonging agents strongly associated with torsade de pointes.
研究组 & 干预措施
Placebo
Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
干预措施: Placebo (Drug)
Placebo
Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
干预措施: Docetaxel (Drug)
Placebo
Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
干预措施: Prednisone (Drug)
Dasatinib
Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
干预措施: Dasatinib (Drug)
Dasatinib
Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
干预措施: Docetaxel (Drug)
Dasatinib
Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
干预措施: Prednisone (Drug)
结局指标
主要结局
Overall Survival: Time From Randomization to Date of Death
时间窗: From randomization to death or date of last contact (maximum reached: 45 months)
Overall survival is defined as time in months from the randomization date to the date of death due to any cause (in the randomized population). If the patient did not die, survival was censored on the last date he or she was known to be alive.
次要结局
- Time to First Skeletal-related Event (SRE)(From day of randomization to date of first SRE or to last SRE assessment, if subsequent cancer therapy begun or no SRE (maximum reached: 42 months))
- Progression-free Survival (PFS)(From day of randomization to disease progression or death (or to last clinical assessment, if subsequent cancer therapy started or no progression or death) (maximum reached: approximately 43 months))
- Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST)(At baseline and every 12 weeks thereafter to end of treatment, at end of treatment, and at follow-up (within 42 days of end of dosing))
- Time to Prostate Specific Antigen (PSA) Progression(From randomization to date of first PSA measurement leading to confirmed PSA progression (or to last bone scan assessment, if no progression or if cancer therapy started) (maximum reached: 30 months))
- Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline(At baseline, prior to each docetaxel infusion (every 3 weeks) to end of treatment, at end of treatment, and at follow-up (within 14 days of end of dosing))
- Percentage of Participants With a Reduction in Pain Intensity From Baseline(At baseline, prior to each docetaxel infusion (every 3 weeks), at end of treatment, and at follow-up (within 14 days of end of dosing))