A Modular Phase I-II Trial of Lenalidomide and Paclitaxel in Men With Castration-Resistant Prostate Cancer and Lymph-Node Dominant Metastases
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of Lenalidomide in Combination with Low-Dose Weekly Paclitaxel
研究概览
简要总结
The goal of the Phase I part of this clinical research study is to find the highest tolerable dose of Revlimid® (lenalidomide) that can be given in combination with paclitaxel to patients with prostate cancer who have failed treatment with taxanes.
The goal of the Phase II part of this clinical research study is to learn if lenalidomide and paclitaxel can help to control prostate cancer.
The safety of this combination treatment will be studied in both phases of the study.
UPDATE:
Study was terminated early due to slow accrual as a Phase I dose escalation study, without progression to Phase II study portion.
详细描述
Study Drugs:
Lenalidomide is a drug that changes the immune system and it may also interfere with the development of tiny blood vessels that help support tumor growth. Taking lenalidomide could prevent the growth of cancer cells.
Paclitaxel is designed to disrupt the growth of cancer cells, which may cause cancer cells to die.
Phases I and II:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined the study. Up to 10 groups of 3 participants will be enrolled in the Phase I portion of the study, and 1 group of up to 42 participants will be enrolled in Phase II.
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
- •Patients with metastatic adenocarcinoma of the prostate
- •Patients in Phase II must have radiographic evidence of multiple (>/= 2) or bulky (>/= 5cm diameter) lymph node metastases with < 2 bone (on radionuclide bone scan) discrete sites of involvement.
- •Patient must have had front-line chemotherapy for castrate-resistant metastatic disease. Any number of prior chemotherapy regimens is permitted, except within the last 3 weeks. No prior thalidomide or lenalidomide therapy is permitted.
- •Patients must have evidence of progression of disease based on any one of the following criteria: a) PSA- progression is defined as 2 consecutive increments in PSA (with an absolute change of at least 1ng/mL) over 4 weeks. b) An increase by 25% of the product of bi-dimensional disease or 30% in maximum diameter or appearance of an unequivocally new lesion qualifies as progression. c) Worsening symptoms clearly attributable to disease progression qualifies as progression e.g. worsening malignant bony pain.
- •Patients on antiandrogens should be discontinued from flutamide, nilutamide or cyproterone acetate for at least 4 weeks and bicalutamide for 6 weeks. If progression is documented during or after this time interval, patients are eligible. Patients who have not had response to deferred (secondary) therapy with antiandrogens do not have to satisfy this waiting period prior to enrollment.
- •Patients must have a performance status of </= 2 (ECOG).
- •Patients will not receive any concurrent biological, immunological, second-line hormonal therapy or chemotherapy. Patients receiving replacement or therapeutic doses of corticosteroid for non-malignant disease while disease progression was established may continue on such therapy.
- •Patients must have recovered from prior chemotherapy, biological or immunological therapy or radiation delivered within the last 28 days. Radioisotope therapy with strontium delivered within the last 90 days or samarium within the last 60 days is not permitted.
- •Patients must have a castrate serum testosterone level (</= 50ng/ml) documented in the last six weeks. For patients who are medically castrated, luteinizing hormone releasing hormone analog must continue to maintain testicular suppression.
- •Patients must have adequate bone marrow function defined as an absolute peripheral granulocyte count of >/= 1,500/mm^3 and platelet count of >/= 75,000/mm^
- •Patients must have adequate hepatic function defined with a bilirubin of </= 2 X upper limits of normal and AST/ALT </= 2.5 X the upper limits of normal.
- •Patients must have adequate renal function defined as creatinine clearance >/= 40 cc/min (measured or calculated by Cockcroft and Gault formula).
- •Must be fully recovered from any previous surgery, in terms of wound healing.
- •Patients must sign an informed consent indicating that they are aware of the investigational nature of this study, in keeping with the policies of the institution.
- •All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
- •Men must agree to use a latex condom during sexual contact with a female of childbearing potential (FCBP) even if they have had a successful vasectomy. A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
- •Patient must be able to take low molecular weight heparin (preferred) OR low-dose enteric aspirin and warfarin for thromboembolic prophylaxis.
排除标准
- •Patients with severe or uncontrolled infection defined as symptomatic and/or requiring intravenous antibiotics.
- •Patients with small cell or sarcomatoid variant of prostate cancer.
- •Patients with symptomatic congestive heart failure (CHF), pulmonary embolus, vascular thrombosis, transient ischemic attack, cerebrovascular accident, unstable angina or MI in the last 3 months or evidence of active myocardial ischemia by symptoms or electrocardiogram (ECG).
- •Known severe hypersensitivity to taxanes.
- •Patients with central nervous system (CNS) metastasis or cord compression are excluded except those patients that have had complete excision or radiotherapy and remain asymptomatic for at least 2 months.
- •Oxygen-dependent lung disease or >/= grade 2 peripheral neuropathy.
- •Known intolerance of corticosteroid therapy that would preclude its use as premedication for paclitaxel.
- •Uncontrolled severe hypertension or uncontrolled diabetes mellitus.
- •Active second malignancies. Non-threatening second malignancies such as superficial low-grade transitional cell carcinoma of the bladder or Rai Stage 0 chronic lymphocytic leukemia or stable small renal cell carcinomas may be exempt from such stipulation at the discretion of the Principal Investigator.
- •Overt psychosis or mental disability or otherwise incompetent to give informed consent. Patients who are unwilling or unable to comply with the RevAssist® program or with a history of non-compliance with medical regimens or who are considered potentially unreliable.
- •Patients with known HIV or active hepatitis A, B, or C infection.
- •Patients receiving any concurrent biological, immunological, second-line hormonal therapy or chemotherapy. Patients receiving replacement or therapeutic doses of corticosteroid for non-malignant disease while disease progression was established may continue on such therapy.
- •Patients who have not recovered from prior chemotherapy, biological or immunological therapy or radiation delivered within the last 28 days. Radioisotope therapy with strontium delivered within the last 90 days or samarium within the last 60 days is not permitted.
研究组 & 干预措施
Lenalidomide and Paclitaxel
Phase I: Up to 5 differing doses of Lenalidomide tested plus fixed dose of Paclitaxel.
Phase II: Lenalidomide at highest tolerated dose from Phase I plus Paclitaxel.
干预措施: Lenalidomide (Drug)
Lenalidomide and Paclitaxel
Phase I: Up to 5 differing doses of Lenalidomide tested plus fixed dose of Paclitaxel.
Phase II: Lenalidomide at highest tolerated dose from Phase I plus Paclitaxel.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of Lenalidomide in Combination with Low-Dose Weekly Paclitaxel
时间窗: After 2, 28 day cycles
MTD defined as dose with posterior mean Pr{toxicity} closest to .33 at the end of the trial, provided that it is not terminated early. The CRM will be implemented using fixed toxicity probabilities (p1, p2, p3, p4, p5) = (.05, .20, .33, .45, .60) under the model Pr{toxicity \| dose level j} = {pj}exp(a) , where a follows a normal prior with mean 0 and variance 2. Dose limiting toxicity (DLT) defined as any of the following treatment-related events occurring within two cycles of therapy (i) uncontrolled or intolerable grade 2 non-hematologic toxicity \> 7 days, (ii) grade 3or 4 nausea/vomiting/diarrhea \> 48 hours, (iii) \> grade 3 fatigue \> 7 days and any other grade 3or 4 non-hematologic toxicity; (iv) grade 4 hematologic toxicity (v) neutropenic fever defined as absolute neutrophil count (ANC) \< 1000 and temperature \>/ 101 degrees F; (vi) any other regimen-related adverse event that precludes delivery of the first two cycles of therapy.
次要结局
- Progression-Free (PFS) Time in Patients with a Lymph Node Dominant Clinical Phenotype(After 2, 28 day cycles)