A Phase II Study of PI-88 With Dacarbazine in Patients With Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 134
- 试验地点
- 12
- 主要终点
- Non-progression Rate After Six Cycles
研究概览
简要总结
The aim of the study is to compare the safety and effectiveness of a new drug called PI-88, when used in combination with an approved chemotherapy drug called dacarbazine, in the treatment of metastatic melanoma.
PI-88 blocks new blood vessel growth in tumours (starves it of nutrients) and dacarbazine stops the cancer cells from growing. The results from this study will be analysed to see if it is worthwhile for the two drugs to be tested in future studies involving larger numbers of melanoma patients.
详细描述
Metastatic melanoma is a difficult-to-treat cancer for which available treatment options are limited and minimally effective. Dacarbazine is currently one of the standard chemotherapy drugs used for the treatment of metastatic melanoma. However, it is associated with low response rates (10-20%) and median survival of less than 12 months (6-11 months in most studies). PI-88 is an antiangiogenic and antimetastatic drug that has already shown some evidence of efficacy when used alone in an intermittent dosage regimen (4 consecutive days per week) in the treatment of patients with advanced melanoma. The FDA has designated PI-88 as an Orphan Drug for this indication, as well as for Stage III and high-risk stage II disease. The aim of this randomised pilot phase II trial is to determine whether PI-88 in combination with a standard regimen of dacarbazine (1000 mg/m2 every 3 weeks) should be considered for further investigation in a larger-scale trial.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven metastatic melanoma
- •Surgery not feasible or inappropriate
- •Measurable disease. Metastatic lesions must be measurable by magnetic resonance imaging (MRI) or computed tomography (CT) as defined in Response Evaluation Criteria in Solid Tumors (RECIST), and cutaneous lesions by physical examination.
- •Have voluntarily given written informed consent to participate in this study
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
- •Life expectancy at least 3 months
- •Neutrophil count > 1.5 x 10^9/L (1,500/mm3)
- •Platelet count > 100 x 10^9/L (100,000/mm3)
- •Acceptable liver function tests (see Exclusion Criteria for maximum allowable elevations of ALT, AST, ALP and LDH)
- •PT < 1.5 x upper limit of normal (ULN)
- •APTT < 1.5 x ULN
- •Creatinine clearance > 40 mL/min, calculated using the Cockcroft-Gault formula (if just below 40 mL/min, then GFR > 40 mL/min as determined by 24-hour urine collection)
排除标准
- •Current or history of central nervous system involvement, brain or meningeal metastases
- •Ocular melanoma
- •Clinically significant non-malignant disease
- •Prior or co-existent malignancies (other than stage I internal malignancy where treated and disease-free for > 5 years, non-melanomatous skin cancer or in situ cancer of the cervix)
- •Prior chemotherapy
- •Prior treatment with vaccines and/or biological response modifiers within the previous 4 weeks
- •Prior treatment with radiotherapy within the previous 4 weeks (local palliative radiotherapy is permitted)
- •Radiotherapy to > 30% of marrow-bearing bone within the previous 3 months
- •Major surgery within the past 4 weeks
- •Concomitant use of aspirin (> 150 mg/day), non-steroidal anti-inflammatory drugs (except specific COX-2 inhibitors), heparin, low molecular weight heparin, warfarin (> 1 mg/day) or anti-platelet drugs (abciximab, clopidogrel, dipyridamole, ticlopidine and tirofiban). Low-dose aspirin (≤ 150 mg/day) and low-dose warfarin (≤ 1 mg/day) are permitted as concomitant medications.
- •Heparin or low molecular weight heparin within the previous 2 weeks
- •History of acute or chronic gastrointestinal bleeding within the last 2 years, inflammatory bowel disease or other abnormal bleeding tendency
- •Patients at risk of bleeding due to open wounds or planned surgery
- •Bilirubin > 1.5 x ULN
- •AST or ALT > 3 x ULN unless patient has hepatic metastases
- •LDH > 2 x ULN
- •Alkaline phosphatase > 5 x ULN, unless patient has bone metastases
- •Myocardial infarction, stroke or congestive heart failure within the past 3 months
- •Women who are pregnant or breast feeding
- •Women of childbearing potential in whom pregnancy cannot be excluded or who are not using an adequate method of contraception
- •History of allergy and/or hypersensitivity to anti-coagulants/thrombolytic agents, especially heparin
- •History of immune-mediated thrombocytopenia, thrombotic thrombocytopenic purpura or other platelet disease, or laboratory evidence of anti-heparin antibodies
- •Uncontrolled or serious infection within the past 4 weeks
- •Patients who are unable to be compliant or to follow instructions given to them by clinic staff
研究组 & 干预措施
Arm 1- PI-88 plus dacarbazine
PI-88 (muparfostat) 190 mg daily by subcutaneous injection and dacarbazine 1000 mg/m2 on day 1 of each 21 day cycle
干预措施: PI-88 and dacarbazine (Drug)
Arm 2- dacarbazine alone
dacarbazine 1000 mg/m2 on day 1 of every 21 day cycle by intravenous infusion
干预措施: dacarbazine or DTIC (Drug)
结局指标
主要结局
Non-progression Rate After Six Cycles
时间窗: In week 3 of every second cycle (each cycle was 21 days) for all subjects enrolled, up to the end of cycle 6 (About 5 months after randomization)
The Proportion of Patients With Objective Response or Stable Disease (Non-progression Rate) after six treatment cycles
次要结局
- Non-progression Rate(In week 3 of every second cycle (each cycle was 21 days) for all subjects enrolled in cycle 2 and cycle 4.)
- Time to Progression(At screening and in week 3 of every second cycle up to the end of cycle 6 and every third cycle after cycle 6 . Each cycle was 21 days.Assessed from date of randomization until the date of first documented progression, up to 50 months.)
- Duration of Response(At screening and in week 3 of every second cycle up to the end of cycle 6 and every third cycle after cycle 6. Each cycle was 21 days. Assessed from date of randomization until the date of first documented progression, up to 50 months.)
- Survival(It was to assess time to death. The time frame is at least 6th month, 12th month and data was continuously collected till the end of the study, up to 50 months..)