Phase I/II Trial to Establish the Safety and Preliminary Efficacy of the Combination of Docetaxel, Prednisone, and SOM 230 (Pasireotide) in Metastatic Castrate Resistant Prostate Cancer (CRPC).
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Pasireotide in Combination With Docetaxel and Prednisone by the Occurrence of Adverse Events and the Associated Grade Per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of pasireotide and to see how well it works when given together with docetaxel and prednisone in treating patients with metastatic hormone-resistant prostate cancer. Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pasireotide may inhibit the secretion of hormones. Giving pasireotide together with docetaxel and prednisone may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose (MTD) level of SOM 230 (pasireotide) in combination with docetaxel and prednisone.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of the combination in metastatic castration-resistant prostate cancer (CRPC).
II. To evaluate preliminary efficacy of the combination of SOM 230 and docetaxel and prednisone as defined by response rates (measurable and prostate-specific antigen [PSA]), time to progression (TTP) and overall survival (OS).
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
- •Histologically confirmed prostate adenocarcinoma with metastasis, and objective progression or rising PSA despite androgen deprivation therapy and antiandrogen withdrawal when applicable; patients with rising PSA must demonstrate a rising trend with 2 successive elevations at a minimum interval of 1 week; a minimum PSA of 5 ng/ml or new areas of bony metastases on bone scan are required for patients with no measurable disease; no minimum PSA requirement for patients with measurable disease
- •Patient must not have received any prior chemotherapy for metastatic disease; all patients must be documented to be castrate with a testosterone level < 0.5 ng/ml; luteinizing hormone-releasing hormone (LHRH) agonist therapy must be continued, if required to maintain castrate levels of testosterone; patients must be off antiandrogens for a minimum of 4 weeks for flutamide and 6 weeks for bicalutamide or nilutamide
- •Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy)
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Life expectancy 12 weeks or more
- •Absolute neutrophil (ANC) >= 1.5 x 10^9/L
- •Platelets >= 100 x 10^9/L
- •Hemoglobin (Hgb) > 9 g/dL
- •Serum bilirubin =< 2 x upper limit of normal (ULN)
- •Serum transaminases activity =< 3 x ULN, with the exception of serum transaminases (< 5 x ULN) if the patient has liver metastases
- •Serum creatinine =< 1.5 x ULN
- •Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
- •Patients must be advised of the importance of using effective birth control measures during the course of the study
- •Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information
排除标准
- •Prior treatment with any cytotoxic chemotherapy, radiation, immunotherapy, or any investigational drug within the preceding 4 weeks
- •Patients who have undergone major surgery within 4 weeks prior to study enrollment
- •Chronic treatment with immunosuppressive agents except steroids
- •Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry
- •Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
- •Patients with prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years
- •Patients with uncontrolled diabetes mellitus, which is defined as a hemoglobin A1C > 8% on therapy or > 7% without therapy, or a fasting plasma glucose > 1.5 ULN; Note: at the principle investigator's discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted
- •Patients with symptomatic cholelithiasis
- •Patients who have congestive heart failure (New York Heart Association [NYHA] Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment
- •QT-related exclusion criteria:
- •Patients with baseline QTc > or = 470 msec
- •History of syncope or family history of idiopathic sudden death
- •Sustained or clinically significant cardiac arrhythmias
- •Patients with risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block
- •Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes or Parkinson's disease), human immunodeficiency virus (HIV), cirrhosis, uncontrolled hypothyroidism or cardiac failure
- •Concomitant medication(s) known to prolong the QT interval
- •Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (enzyme-linked immunosorbent assay [ELISA] and Western blot)
- •Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- •Severely impaired lung function
- •Any active (acute or chronic) or uncontrolled infection/ disorders
- •Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
- •Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide long-acting release (LAR) formulations
- •History of noncompliance to medical regimens
- •Patients unwilling to or unable to comply with the protocol
- •Men and any female partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation and for additional 2 months after finishing therapy; should a patient's sexual partner become pregnant or suspect she is pregnant while patient is participating in this study, he should inform the treating physician immediately
研究组 & 干预措施
Treatment (chemotherapy, receptor agonist)
Patients receive pasireotide IM, 40 mg on day 1, docetaxel 75mg/m2 IV over 1 hour, and prednisone 5mg PO BID continuously. Courses with docetaxel repeat every 21 days and courses with pasireotide repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: docetaxel (Drug)
Treatment (chemotherapy, receptor agonist)
Patients receive pasireotide IM, 40 mg on day 1, docetaxel 75mg/m2 IV over 1 hour, and prednisone 5mg PO BID continuously. Courses with docetaxel repeat every 21 days and courses with pasireotide repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pasireotide (Drug)
Treatment (chemotherapy, receptor agonist)
Patients receive pasireotide IM, 40 mg on day 1, docetaxel 75mg/m2 IV over 1 hour, and prednisone 5mg PO BID continuously. Courses with docetaxel repeat every 21 days and courses with pasireotide repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: prednisone (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Pasireotide in Combination With Docetaxel and Prednisone by the Occurrence of Adverse Events and the Associated Grade Per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
时间窗: Up to day 57
To identify the maximum tolerated dose (MTD) of pasireotide, The occurrence rate of binary endpoints (eg, specific types of toxicity at a certain dose level and severity grade, response, etc) will be described by point estimates and exact 90% confidence intervals (CIs) for proportions using Wilson's method.
次要结局
- Percentage Prostate-specific Antigen (PSA) Change Noted(On days 1, 22, 43)
- Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy(Baseline and days 22 and 43)
- Measurements of Tumor Using Response Evaluation Criteria In Solid Tumors (RECIST) Criteria Before and After Treatment With the Combination of Pasireotide in Combination With Docetaxel(Every 12 weeks for the first 36 weeks and then every 16 weeks thereafter up to 100 weeks)
- The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0(On days 1, 8, 15, 22, 29, 36 43, 50 and 57)
- Time to Progression (TTP)(Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study, up to 2 years)
- Pharmacokinetics (PK) of SOM230(Predosing/end of infusion/2, 3, 4 ,7, 24 and 48 hours after start of docetaxel; Day 43; predosing for docetaxel and pasireotide/end of infusion/2, 3, 4, 7, 24 hours day 44/48 hours day 45 after start of infusion; days 29, 57, and 85 prior to pasireotide)
- Overall Survival (OS)(Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study)
- Measurements of CTC Counts, the Change Between Time-points Pre-therapy, Post-therapy(Baseline and days 22 and 43)
研究者
Elisabeth Heath
Principal Investigator
Barbara Ann Karmanos Cancer Institute