A Phase I/II Trial of Concurrent Chemohormonal Therapy Using Enzalutamide (MDV-3100) and Cabazitaxel in Patients With Metastatic Castration Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 37
- 试验地点
- 3
- 主要终点
- Percentage of Participants With Dose Limiting ToxicitiesGgraded by National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (Phase I)
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of cabazitaxel when given together with enzalutamide in treating patients with prostate cancer that has spread to other places in the body (metastatic) and has not responded to treatment with hormones or no longer responds to treatment with hormones (hormone-resistant). Drugs used in chemotherapy, such as cabazitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Androgen can cause the growth of prostate cancer cells. Hormone therapy using enzalutamide may fight prostate cancer by blocking the use of androgen by the tumor cells. Giving cabazitaxel together with enzalutamide may work better in treating metastatic, hormone-resistant prostate cancer.
详细描述
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of combination treatment with enzalutamide and cabazitaxel (as determined by percent dose limiting toxicities [DLT], where DLT < 17% is consistent with it being a tolerable combination).
II. To determine the efficacy of treatment with the hormonal agent enzalutamide and the chemotherapy cabazitaxel in combination in men with metastatic castration-resistant prostate cancer (CRPC) (as determined by percent of patients achieving >= 90% prostate specific antigen [PSA] declines following initiation of treatment).
SECONDARY OBJECTIVES:
I. To further define the anticancer effect and safety profile of the combination of enzalutamide and cabazitaxel.
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
- •Metastatic CRPC
- •Willing to provide a tumor sample via biopsy from a metastatic site of disease to be collected at screening if safe and feasible per discretion of treating investigator; adequate archival metastatic tissue can be used, if available, in lieu of baseline biopsy if done when patient had CRPC; patients without a site amenable to biopsy and lack of archival tissue may still join the study
- •Evidence of prostate cancer progression by any of the following criteria: radiographic or PSA criteria, or symptomatic progression related to prostate cancer
- •Castrate testosterone levels (< 50 ng/dL) achieved by orchiectomy or maintenance on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist
- •Histologic confirmation of original prostate cancer diagnosis per institutional standard; life expectancy of greater than 6 months
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Leukocytes >= 3,000/mm^3
- •Absolute neutrophil count >= 1,500/mm^3
- •Platelets >= 100,000/mm^3
- •Total bilirubin within normal institutional limits (or < 2 X the upper limit of normal in those with Gilbert's disease)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 X institutional upper limit of normal
- •Creatinine within less than the institutional upper limit of normal
- •Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Subject agrees to use a double barrier method of birth control during the course of study treatment period with enzalutamide and/or cabazitaxel treatment and for at least 3 months after the study is discontinued
- •A double-barrier method of contraception involves the use of a condom in combination with 1 of the following: contraceptive sponge, diaphragm, or cervical ring with spermicidal gel or foam
- •Subject who has had a vasectomy at least 6 months prior to starting study treatment period and those whose female sexual partner(s) are more than 55 years of age and postmenopausal for at least 2 years or surgically sterile (tubal ligation, hysterectomy, or bilateral oophorectomy) agree to use at least a condom
- •Ability to understand, and the willingness to sign, a written informed consent document, as well as comply with study requirements
- •Must have appropriate wash out (> 6 half-lives) of androgen receptor antagonists, 5 alpha reductase inhibitors or ketoconazole prior to the start of cycle 1; if the agent is not in the table below, the washout should be 2 weeks
- •Bicalutamide; approximate half-life: 6 days; washout period required: 36 days
- •Flutamide; approximate half-life: 6 hours; washout period required: 36 hours
- •Nilutamide approximate half-life: 4 days; washout period required: 24 days
- •Finasteride; approximate half-life: 8 hours; washout period required: 48 hours
- •Aminoglutethimide; approximate half-life: 15 hours; washout period required: 4 days
- •Ketoconazole; approximate half-life: 8 hours; washout period required: 48 hours
排除标准
- •Prior chemotherapy for mCRPC prostate cancer; chemotherapy given neoadjuvantly, adjuvantly, or for hormone sensitive metastatic disease is permitted as long as the cancer did not progress on chemotherapy AND > 6 months have elapsed
- •Patients may not have received any other investigational agents within the last 14 days at the time of treatment start
- •Patients may not have received enzalutamide or ARN-509 (another androgen receptor antagonist) in the past
- •Patients may not have received cabazitaxel in the past
- •Subject has clinical signs suggestive of high or imminent risks for pathological fracture, spinal cord compression and/or cauda equina syndrome
- •History of severe hypersensitivity reaction (>= grade 3) to docetaxel, polysorbate 80 containing drugs, or any of the capsule components of enzalutamide, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene
- •Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 family 3, subfamily A, polypeptide 4/5 (3A4/5); (a one-week wash-out period is necessary for patients who are already on these treatments)
- •Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Subject has a history of seizure or any condition that may predispose to seizure including, but not limited to, underlying brain injury, stroke in the past 6 months, primary brain tumors, brain metastases, prior seizures
- •Subject has a history of unexplained loss of consciousness or transient ischemic attack within 12 months of treatment start
- •Subject is unwilling to stop using herbal supplements that can affect the PSA, such as saw palmetto or prostate cancer (PC)-SPES
- •Subject has another active malignancy other than non-melanomatous skin cancer (unless it is metastatic) or superficial bladder cancer
- •Must not have a gastrointestinal condition that would interfere with absorption
- •Subjects may not be on other therapies that affect hormone levels, such as estrogens, testosterones, ketoconazole during this study; however, megestrol for hot flashes is permitted
研究组 & 干预措施
Treatment (cabazitaxel, enzalutamide)
Patients receive cabazitaxel IV over 1 hour on day 1 and enzalutamide PO QD on days 1-21 (days 2-21 of cycle 1). Patients also receive prednisone PO BID as standard of care with cabazitaxel. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue enzalutamide PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity.
干预措施: Cabazitaxel (Drug)
Treatment (cabazitaxel, enzalutamide)
Patients receive cabazitaxel IV over 1 hour on day 1 and enzalutamide PO QD on days 1-21 (days 2-21 of cycle 1). Patients also receive prednisone PO BID as standard of care with cabazitaxel. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue enzalutamide PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity.
干预措施: Prednisone (Drug)
Treatment (cabazitaxel, enzalutamide)
Patients receive cabazitaxel IV over 1 hour on day 1 and enzalutamide PO QD on days 1-21 (days 2-21 of cycle 1). Patients also receive prednisone PO BID as standard of care with cabazitaxel. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue enzalutamide PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (cabazitaxel, enzalutamide)
Patients receive cabazitaxel IV over 1 hour on day 1 and enzalutamide PO QD on days 1-21 (days 2-21 of cycle 1). Patients also receive prednisone PO BID as standard of care with cabazitaxel. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue enzalutamide PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (cabazitaxel, enzalutamide)
Patients receive cabazitaxel IV over 1 hour on day 1 and enzalutamide PO QD on days 1-21 (days 2-21 of cycle 1). Patients also receive prednisone PO BID as standard of care with cabazitaxel. Cycles repeat every 21 days for 6-10 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue enzalutamide PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity.
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Percentage of Participants With Dose Limiting ToxicitiesGgraded by National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (Phase I)
时间窗: Up to 42 days
The percentage of participants will be reported with 95% confidence interval using exact method.
PSA Response 1, Defined as >= 90% PSA Decline From Baseline
时间窗: Baseline to time of >= 90% PSA decline, assessed up to 68 weeks
The percentage of participants with a \>= 90% PSA decline from baseline will be reported with 95% confidence interval using exact method. 'PSA response' is based on Prostate Cancer Working Group 2's (PCWG2) recommendations, which do not offer a specific definition as no single degree of decline has been established.
次要结局
- Incidence of Adverse Events Graded by National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0(Up to 28 days after the last dose of study medication)
- Pharmacokinetic Parameters of Cabazitaxel: Mean Cabazitaxel Half-Life(Day 1 at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the start of cabazitaxel infusion of cycles 1 and 2 (each cycle is 21 days))
- PSA Response 2, Defined as >= 50% PSA Decline From Baseline(Baseline to time of >= 50% PSA decline, assessed up to 68 weeks)
- Pharmacokinetic Parameters of Cabazitaxel: Max Plasma Concentration (Cmax)(Day 1 at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the start of cabazitaxel infusion of cycles 1 and 2 (each cycle is 21 days))
- Pharmacokinetic Parameters of Cabazitaxel: Mean Area Under the Curve (AUC)(Day 1 at 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the start of cabazitaxel infusion of cycles 1 and 2 (each cycle is 21 days))
- Overall Survival(Up to 5 years)
- PSA Response 3, Defined as >= 30% PSA Decline From Baseline(Baseline to time of >= 30% PSA decline, assessed up to 68 weeks)
研究者
Julie Graff
Principal Investigator
OHSU Knight Cancer Institute