A Phase 2 Randomized Study of Cediranib (AZD2171) Alone Compared With the Combination of Cediranib (AZD2171) Plus BMS-354825 (Dasatinib, Sprycel) in Docetaxel Resistant, Castration Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 8
- 主要终点
- 12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2)
研究概览
简要总结
This randomized phase II trial is studying the side effects and how well giving cediranib maleate together with or without dasatinib works in treating patients with hormone-resistant prostate cancer resistant to treatment with docetaxel. Cediranib maleate and dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. It is not yet known whether giving cediranib maleate together with dasatinib or alone is an effective treatment for prostate cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine the progression-free survival of patients with docetaxel-resistant and castration-resistant prostate cancer treated with cediranib maleate with versus without dasatinib.
SECONDARY OBJECTIVES:
I. To confirm the safety and tolerability of cediranib maleate with versus without dasatinib in these patients.
II. To calculate objective response rates of cediranib maleate with versus without dasatinib, according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in patients with measurable disease at baseline.
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/cytologically confirmed prostate cancer
- •Measurable/non-measurable disease
- •Prior hormonal therapy with medical LHRH agonist or orchiectomy castration (Castrate level of testosterone (< 50 ng/dL) required)
- •Clinical/radiographic evidence of progression on or after docetaxel therapy
- •No active pleural/pericardial effusion of any grade
- •No meningeal metastases/untreated known brain metastases
- •Patients with treated brain metastasis with radiologic, clinical evidence of stability, with no evidence of cavitation/hemorrhage in the brain lesions allowed if asymptomatic and not requiring corticosteroids
- •Life expectancy >3 months
- •ECOG PS 0-2 (Karnofsky PS 60-100%)
- •ANC >= 1,500/mm^3
- •Platelet count >= 100,000/mm^3
- •Hemoglobin >= 9 g/dL
- •INR=< 1.3
- •Total bilirubin =< 1.25 times ULN
- •AST and ALT=< 2.0 times ULN (5 x ULN if clearly attributable to liver metastasis)
- •Creatinine normal OR creatinine clearance >= 60 mL/min
- •LVEF> institutional normal range by ECHO/MUGA
- •Urine dipstick for protein < 1+ OR < 1 g on 24-hour urine collection
排除标准
- •>5 years since any malignancy except in situ cancer, non-metastatic basal/squamous cell skin cancer, or other cancer for which the patient has been curatively treated
- •Fertile patients must use effective contraception
- •No condition that impairs ability to swallow/absorb
- •No history of allergic reactions attributed to compounds of similar chemical/biologic composition to cediranib/dasatinib
- •No systolic BP>150 mmHg and/or diastolic BP>100 mmHg
- •QTc prolongation (>=480 msec by Fridericia correction) or other significant ECG abnormalities are ineligible
- •No active/uncontrolled infections, serious illness, or medical conditions that would not permit patient to be managed according to protocol
- •No known immunodeficiency syndrome
- •No clinical/radiological evidence of severe/uncontrolled interstitial lung disease
- •No history/concurrent idiopathic pulmonary fibrosis
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No unresolved toxicity>=CTCAE grade 2 (except alopecia) from prior anticancer therapy
- •4 weeks since prior anti-androgens
- •4 weeks since prior chemotherapy following docetaxel for metastatic disease (Any number of regimens allowed)
- •4 weeks since prior hormonal therapy or abiraterone
- •3 weeks since prior radioisotopes or radiotherapy and recovered
- •No prior therapy with angiogenesis or Src or FAK inhibitors
- •3 weeks since prior major surgery and recovered
- •1 week since prior corticosteroids
- •Concurrent zoledronic acid allowed provided patient has been receiving it prior to start of study treatment
- •Concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of cediranib and dasatinib will be determined following review of their case by the principal investigator or co-investigator
- •14 days before and after study and no concurrent CYP3A4-active agents or substances (including strong inhibitors or inducers)
- •Concurrent prophylactic low-dose warfarin (INR must be close monitored) or low-molecular weight heparin allowed
- •No other concurrent investigational agents
研究组 & 干预措施
Arm I
Patients receive oral cediranib maleate once daily and oral dasatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: cediranib maleate (Drug)
Arm I
Patients receive oral cediranib maleate once daily and oral dasatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: dasatinib (Drug)
Arm II
Patients receive cediranib maleate as in arm I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: cediranib maleate (Drug)
结局指标
主要结局
12-week Progression-free Survival as Per the Prostate Cancer Clinical Trials Working Group (PCWG2)
时间窗: 3 months
Progression is defined using the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, which includes a compilation of prostate-specific antigen (PSA), bone scan, and CT-scan assessments (Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- Number of Participants With Toxicities(Up to 30 days after last dose of study drugs)
- Qualtiy of Life Assessment Number of Participants With a Score ≥2 on the Present Pain Intensity (PPI) Scale(After every cycle (median duration on study = 4 cycles))
- Number Who Experienced Study Medication Dose Intensity(Cycle 1 (an average of 28 days))
- Treatment Discontinuation(Cycle 1 (average of 28 days))
- Treatment Discontinuation Due to Adverse Events (AEs)(Through study completion (median duration on study = 4 cycles))
- Non-AE Related Treatment Discontinuation(Through study completion (median duration on study = 4 cycles))
- Overall Response Rate(Duration of Study (median duration on study = 4 cycles))
- Treatment Related Deaths(Through study completion (median duration on study = 4 cycles))
- Participants for Which Bone Biomarkers for Beta-C Telopeptide Was Reduced(Through study completion (median duration on study = 4 cycles))
- Number of Participants With Increased Alkaline Phosphatase BAP(Through study completion (median duration on study = 4 cycles))
- Dose Interruption Due to AEs(Through study completion (median duration on study = 4 cycles))
- Dose Reductions(Duration of Study (median duration on study = 4 cycles))
- Quality of Life Assessment Using Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire(Up to 16 weeks)