NCT00683475已完成2 期
A Phase 2, Multicenter, Randomized Study of IMC-A12 or IMC-1121B Plus Mitoxantrone and Prednisone in Metastatic Androgen-Independent Prostate Cancer (AIPC) Following Disease Progression on Docetaxel-Based Chemotherapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Composite Progression-free Survival (cPFS)
研究概览
简要总结
The purpose of this study is to determine whether IMC-A12 or IMC-1121B (ramucirumab) with Mitoxantrone and Prednisone is effective in the treatment of metastatic androgen- independent prostate cancer (APIC).
详细描述
Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of cancer-related death in men in the United States. Chemotherapy, either as a single agent or in combination, may lead to clinical response, pain control, and/or improved quality of life. Docetaxel is now the first-line standard therapy for AIPC. Mitoxantrone was approved in 1996 for use in combination with corticosteroids as initial chemotherapy for pain related to advanced Hormone Refractory Prostate Cancer (HRPC). Hormonal manipulations and docetaxel-based chemotherapy are often effective in metastatic prostate cancer; however, disease becomes refractory to these interventions in the majority of men. Although mitoxantrone continues to be a significant agent in the treatment of HRPC, there exists a need for more efficacious therapy in docetaxel-refractory- AIPC. Because of the potential contribution of Insulin Like Growth Factor Receptor (IGF-IR) and VEGFR-2 mediated pathways in prostate cancer pathogenesis, it is hypothesized that each of these biological agents in combination with mitoxantrone and prednisone will result in clinically meaningful activity in AIPC. Therefore, ImClone plans to conduct a randomized Phase 2 trial to assess the safety and efficacy of IMC-A12 or IMC-1121B (ramucirumab) in combination with mitoxantrone and prednisone in participants with AIPC.
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
- •The participant has histologically-confirmed adenocarcinoma of the prostate
- •The participant has radiographic evidence of metastatic prostate cancer (stage M1 or D2)
- •The participant has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent)
- •The participant has had disease progression (clinical or radiographic) while receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent
- •The participant must have evidence of progressive disease defined as at least one of the following;
- •Progressive measurable disease: using conventional solid tumor criteria
- •Bone scan progression: at least two new lesions on bone scan
- •Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2
- •The participant has a PSA ≥ 2 ng/mL
- •The participant has prior surgical or medical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment
- •The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2
- •The participant has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)
- •The participant has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal (ULN), Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present)
- •The participant has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min)
- •The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study
- •The participant has adequate coagulation function (an international normalized ratio [INR] ≤ 1.5 and a Partial Thromboplastin Time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Participants receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3)
- •The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN
排除标准
- •The participant has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)
- •The participant has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted)
- •The participant has a history of symptomatic congestive heart failure or has a pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN
- •The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab
- •The participant is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration
- •The participant has known or suspected brain or leptomeningeal metastases
- •The participant has uncontrolled or poorly controlled hypertension
- •The participant has poorly controlled diabetes mellitus. Inclusion Criteria:
- •The participant has histologically-confirmed adenocarcinoma of the prostate
- •The participant has radiographic evidence of metastatic prostate cancer (stage M1 or D2)
- •The participant has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent)
- •The participant has had disease progression (clinical or radiographic) while receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent
- •The participant must have evidence of progressive disease defined as at least one of the following;
- •Progressive measurable disease: using conventional solid tumor criteria
- •Bone scan progression: at least two new lesions on bone scan
- •Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2
- •The participant has a PSA ≥ 2 ng/mL
- •The participant has prior surgical or medical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment
- •The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2
- •The participant has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)
- •The participant has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate transaminase [AST] and alanine transaminase [ALT]≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present)
- •The participant has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min)
- •The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study
- •The participant has adequate coagulation function (an international normalized ratio [INR] ≤ 1.5 and a partial thromboplastin time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Participants receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3)
- •The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN
- •Exclusion Criteria:
- •The participant has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)
- •The participant has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted)
- •The participant has a history of symptomatic congestive heart failure or has a pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN
- •The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab
- •The participant is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration
- •The participant has known or suspected brain or leptomeningeal metastases
- •The participant has uncontrolled or poorly controlled hypertension
- •The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition
- •The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition
- •The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
研究组 & 干预措施
IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone
Experimental
干预措施: Mitoxantrone (Drug)
IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone
Experimental
干预措施: Prednisone (Drug)
IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone
Experimental
干预措施: IMC-1121B (ramucirumab) (Biological)
IMC-A12 + Mitoxantrone + Prednisone
Experimental
干预措施: IMC-A12 (Biological)
IMC-A12 + Mitoxantrone + Prednisone
Experimental
干预措施: Mitoxantrone (Drug)
IMC-A12 + Mitoxantrone + Prednisone
Experimental
干预措施: Prednisone (Drug)
结局指标
主要结局
Composite Progression-free Survival (cPFS)
时间窗: Randomization to composite progressive disease, up to 23.4 months
Defined as the median time from randomization to the earliest of: 1. Tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST); 2. Evidence of progression by bone scan, performed after completion of the first 3 cycles, demonstrating the appearance of \>=2 new lesions; 3. New skeletal events (New pathologic bone fracture in the region of metastatic disease; New bone lesion requiring radiation or surgery; Spinal cord or nerve root compression) 4. Symptomatic progression (for participants without measurable disease); 5. Other clinical events attributable to prostate cancer that require major interventions; or 6. Death from any cause Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.
次要结局
- Prostate Specific Antigen (PSA) Response Rate(Baseline up to data cut-off date (up to 36.3 months))
- Maximum Concentration (Cmax) at Study Day 1(Day 1)
- Maximum Concentration (Cmax) at Study Day 15(Day 15)
- Maximum Concentration (Cmax) at Study Day 30(Day 30)
- Summary Listing of Participants Reporting Treatment-Emergent Adverse Events(Randomization to 36.3 months)
- Maximum Concentration (Cmax) at Study Day 16(Day 16)
- Composite Progression-free Survival (cPFS) at 6-months(6 months)
- Overall Survival (OS)(First dose to death due to any cause up to 36.3 months)
- Time to Radiographic Evidence of Disease Progression(Randomization to date of radiographic progression, up to 36.3 months)
- Composite Progression-free Survival (cPFS) at 9-months(9 months)
- Composite Progression-free Survival (cPFS) at 12-months(12 months)
- Minimum Concentration (Cmin) at Study Day 30(Day 30)
- Objective Response Rate (ORR)(Baseline to date of progressive disease or death up to 36.3 months)
- Minimum Concentration (Cmin) at Study Day 1(Day 1)
- Minimum Concentration (Cmin) at Study Day 15(Day 15)
- Minimum Concentration (Cmin) at Study Day 16(Day 16)
研究者
研究点 (1)
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