Open-label, multicenter, multi-national, phase III study to assess the safety of RO5185426 in patients with BRAF V600 mutation-positive (identified by the cobas 4800 BRAF V600 Mutation Test) metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV; AJCC).
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 900
- 试验地点
- 7
- 主要终点
- patients with metastatic melanoma (surgically incurable and
研究概览
简要总结
Summary
Metastatic melanoma represents a major clinical challenge as it is an essentially incurable disease with few satisfactory treatment options. Current first-line treatment options have yielded low response rates and no evidence of impact on survival. In the second-line setting, no treatment is considered effective and response rates to agents after first-line failure are very low (section
1.1.1).RO5185426 is a highly selective inhibitor of the oncogenic BRAF kinase which has been identified in a large number of malignant melanomas. Results from Phase I and II studies have shown that RO5185426 induces high response rates in patients with metastatic melanoma carrying the V600E BRAF mutation (section
1.1.3). Results from the phase 3 study show an OS and PFS benefit in patients with unresectable IIIC or stage IV metastatic melanoma. These data indicate that RO5185426 might be an effective treatment option in this patient population with no currently available satisfactory treatment options. The purpose of this multicenter, early access study is to make RO5185426 available to a larger number of patients than could otherwise be treated in registration trials and who are without satisfactory treatment options. The primary objective of this study will be to evaluate the safety of RO5185426 in patients with unresectable IIIC or stage IV metastatic melanoma positive for the V600 BRAF mutation (identified by the cobas® 4800 BRAF V600 Mutation Test).Study Overview:
This is an open-label, multicenter, multi-national, expanded access study of RO5185426 in patients with BRAF V600 mutation-positive (identified by the cobas
® 4800 BRAF V600 Mutation Test) metastatic melanoma who may or may not have received priortherapy for metastatic melanoma. The primary objective of this study is to assess the safety and tolerability of RO5185426. The study population will consist of patients at least 16 years of age with histological confirmed diagnoses of metastatic melanoma harboring the BRAF V600 mutation, as determined by cobas
® 4800 BRAF V600 Mutation Test. Patients with measurable and/or non-measurable disease (as defined by RECIST 1.1) are eligible for enrollment in this trial. Patients may or may not have received prior therapy for metastatic melanoma. The trial will consist of a screening period (Day –28 to Day 1), a treatment phase, and an end of study/follow up. Day 1 of the study will be defined as the first day a patient receives RO5185426. One cycle of therapy is defined as 28 days of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Not Applicable
入排标准
- 年龄范围
- 16.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion Criteria:
- •Male or female patients ≥ 16 years of age
- •Patients with histologically confirmed metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV; AJCC) with documented BRAF V600 mutation determined by the cobas® 4800 BRAF V600 Mutation Test prior to administration of RO
- •Unresectable stage IIIC disease must have confirmation from a surgical oncologist
- •Patients with either measurable or non- measurable disease(RECIST Version 1.1)
- •Patients may or may not have received prior systemic therapy for metastatic melanoma
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
- •Patients must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma
- •Adequate hematologic, renal and liver function as defined by the following laboratory values performed within 7 days prior to first dose of RO5185426: • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L • Platelet count ≥ 100 x 109/L • Hemoglobin ≥ 9 g/dL • Serum creatinine ≤ 1.5 times upper limit of normal (ULN) or creatine clearance (CrCl) > 50 mL/hr by Cockroft–Gault formula • Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) ≤ 2.5 times ULN (≤ 5times ULN if considered due to tumor) • Serum bilirubin ≤ 1.5 times ULN • Alkaline phosphatase ≤ 2.5 times ULN (≤ 5times ULN if considered due to tumor)
- •Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women.
- •Women of non- childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year.
- •Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician.
- •Effective methods of contraception are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices).
- •At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance.[Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.] 10.Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry 11.Signed informed consent must be obtained prior to performing any study-related procedures (including tumor testing for the V600 BRAF mutation).
排除标准
- •Evidence of symptomatic CNS lesions as determined by investigator (patients with radiographically stable, asymptomatic lesions previously irradiated or surgically resected are eligible)
- •Patients with a previous malignancy (other than melanoma) within the past 2 years are excluded except patients with treated and controlled basal or squamous cell carcinoma (SCC) of the skin or carcinoma in-situ of the cervix.
- •Isolated elevation in prostate- specific antigen in absence of radiographic evidence of metastatic prostate cancer is allowed
- •Concurrent administration of any anti-cancer therapies (e.g. chemotherapy, other targeted therapy, experimental drug, etc) other than those administered in this study
- •Known hypersensitivity to RO5185426 or another BRAF inhibitor
- •Pregnant or lactating women
- •Refractory nausea and vomiting,malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption.
- •Patients must be able to swallow tablets
- •Any of the following within the 6 months prior to first RO5185426 administration: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, hypertension not adequately controlled by current medications
- •History of congenital long QT syndrome, history or presence of clinically significant ventricular or atrial dysrhythmias ≥ Grade 2 (NCI CTCAE Version 4.0)
- •Corrected QT (QTc) interval ≥ 450 msec at baseline 10.Uncontrolled medical illness (such as infection requiring treatment with intravenous (IV) antibiotics).
结局指标
主要结局
patients with metastatic melanoma (surgically incurable and
时间窗: N/A
To evaluate the safety and tolerability of RO5185426 in
时间窗: N/A
unresectable stage IIIC or stage IV; AJCC) harboring the BRAF V600 mutation.
时间窗: N/A
次要结局
- To evaluate the efficacy of RO5185426 as overall(response rates (ORRs) determined by the investigator (RECIST,)