A Randomized, Double-Blind, Multicenter Study Comparing MDX-010 Monotherapy, MDX-010 in Combination With a Melanoma Peptide Vaccine, and Melanoma Vaccine Monotherapy in HLA-A2*0201-Positive Patients With Previously Treated Unresectable Stage III or IV Melanoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,783
- 试验地点
- 183
- 主要终点
- Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone
研究概览
简要总结
The purpose of this study is to determine the safety and efficacy of MDX-010 (ipilimumab, BMS-734016) (anti-CTLA4) in combination with MDX-1379 (gp100, BMS-734019) in patients with previously treated, unresectable Stage III or IV melanoma. Survival time will be evaluated, as well as patient responses and time to disease progression. Eligible patients are those who in response to a single regimen containing interleukin-2 (IL-2), dacarbazine, and/or temozolomide, have 1) relapsed following an objective response (partial response/complete response [PR/CR]); 2) failed to demonstrate an objective response (PR/CR); or 3) could not tolerate such a regimen due to unacceptable toxicity. Patients will be randomized into one of three groups, and will receive one of the following treatments: MDX-010 alone, MDX-1379 alone, or MDX-010 in combination with MDX-1379.
详细描述
Melanoma accounts for approximately 5% of all skin cancers in the United States, but it accounts for about 75% of all skin cancer deaths. In 2004, the expected prevalence of melanoma is 627,252, with about 119,178 of these cases being Stage III or IV (metastatic melanoma). First line treatments for metastatic melanoma, usually IL-2, dacarbazine and/or temozolomide, are associated with significant toxicities. MDX-010 (anti-CTLA4) antibodies are designed to keep the immune system running by blocking CTLA-4 from down-regulating T cell activation. MDX-1379 is made up of two peptides that are pieces of a bigger melanoma protein (gp100). These peptides bind to HLA-A2 which is then recognized by T cells.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Diagnosed with malignant melanoma
- •Measurable unresectable Stage III or IV melanoma
- •HLA-A*0201 positive
- •Previous treatment with & failure/relapse/inability to tolerate IL-2, dacarbazine and/or temozolomide
- •At least 4 weeks since prior treatment
- •Negative pregnancy
- •Life expectancy greater than 4 months
- •Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1
- •Required lab values
- •Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) negative
排除标准
- •Prior malignancies which the patient has not been disease free for over 5 years, except treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer
- •Ocular melanoma
- •Active, untreated central nervous system (CNS) metastasis
- •Prior treatment with MDX-010 (anti-CTLA4) antibody
- •Prior treatment with any cancer therapeutic vaccine
- •Active autoimmune disease or history of autoimmune disease
- •Pregnancy or nursing
- •Hypersensitivity to Incomplete Freund's Adjuvant (IFA) (Montanide ISA-51)
- •Underlying medical conditions deemed hazardous if treated with study drug
- •Concomitant therapy with anti-melanoma drugs, chemotherapies, other investigational therapies, chronic use of systemic corticosteroids
- •Unable to provide informed consent
研究组 & 干预措施
1
Melanoma Peptide Vaccine (MDX-1379) (gp100) + Placebo
干预措施: MDX-1379 (gp100) Melanoma Peptide Vaccine (Biological)
2
MDX-010 (ipilimumab) + MDX-1379 (gp100) (Melanoma Peptide Vaccine)
干预措施: MDX-010 (anti-CTLA4) monoclonal antibody (Drug)
2
MDX-010 (ipilimumab) + MDX-1379 (gp100) (Melanoma Peptide Vaccine)
干预措施: MDX-1379 (gp100) Melanoma Peptide Vaccine (Biological)
3
MDX-010 (ipilimumab) + Placebo
干预措施: MDX-010 (anti-CTLA4) monoclonal antibody (Drug)
结局指标
主要结局
Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone
时间窗: From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks)
OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
次要结局
- Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 Monotherapy Versus gp100 Melanoma Peptide Vaccine Alone and MDX-010 in Combination With gp100 Melanoma Peptide Vaccine Versus MDX-010 Monotherapy(From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks))
- 12-, 18-, and 24-Month Survival Rates(Month 12, Month 18, Month 24)
- Progression Free Survival (PFS)(From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks))
- Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24(Week 12, Week 24)
- Time to Progression (TTP)(from time of randomization to date of PD or death due to PD (end of the study was defined as the time at which 481 deaths were observed [264 weeks]))
- Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD)(BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1.)
- Determination of Best Overall Response Rate (BORR)(Up to week 24)
- Time to Response(From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks))
- Duration of Response(from time of initial drug administration to date of PD or death due to PD (the end of the study was defined as the time at which 481 deaths were observed [264 weeks]))
- Disease Control Rate (DCR)(Up to week 24)
- Delayed Response (Response Beyond Week 24)(from Week 24 to end of study (the end of the study was defined as the time at which 481 deaths were observed [264 weeks]))
- Change From Baseline in Health-Related Quality of Life (QOL) as Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Instrument at Week 12(Baseline (Day 1, Cycle1), Week 12)
- Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death(On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).)
- Percentage of Participants With Immune-Related Adverse Events (irAEs)(On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).)
- Percentage of Participants With Worst On-Study Hematological Abnormalities(On-study laboratory results are results reported after the first dose date and within 70 days of last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).)
- Percentage of Participants With Worst On-Study Liver Abnormalities(On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).)
- Percentage of Participants With Worst On-Study Renal Abnormalities(On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]).)
- Clinically Meaningful Changes in Vital Signs and Physical Examinations(vital signs and physical examination were evaluated at screening and at Weeks 1, 4, 7, 10, 12, 16, 20, 24, 28, 36, and every 3 months thereafter)