A Phase I/II Study of Safety and Efficacy of Ribociclib (LEE011) in Combination With Trametinib (TMT212) in Patients With Metastatic or Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 95
- 试验地点
- 7
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Phase Ib dose escalation in advanced solid tumors to identify dose for Phase II dose expansion in advanced or metastatic pancreatic cancer and KRAS-mutant colorectal cancer. Open-label, nonrandomized.
详细描述
Upon careful review of all available efficacy and safety data from the study phase Ib part, Novartis decided to not start the study phase II part.
This decision was in no means triggered by an unfavorable safety profile of the combination. The observed safety profile of the combination represents contributions of the individual safety profile of trametinib and ribociclib.
No new safety signals were observed.
The study was closed early in line with protocol Section 4.4.
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
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Phase II only:
- •Patient has received prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.
- •Phase I and Phase II:
- •Patient with a known hypersensitivity to the study drugs or any of the excipients of ribociclib or trametinib.
- •Patient is concurrently using other anti-cancer therapy.
- •Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to Cycle 1 Day 1
- •Patient has received local therapy to liver ≤ 3 months of C1D1
- •History of liver disease as follow:
- •Cirrhosis
- •Autoimmune hepatitis
- •Active viral hepatitis
- •Portal hypertension
- •Drug induced liver steatosis
- •Prior systemic anti-cancer treatment within 28 days prior to Cycle 1 Day 1
- •Prior therapy with anthracyclines at cumulative doses of 450 mg/ m2 or more for doxorubicin or 900 mg/m2 or more for epirubicin.
- •Patient is currently receiving warfarin or other coumadin derived anti-coagulant
- •Patient has a history of deep venin thrombosis or pulmonary embolism within 6 months of screening.
- •Patient has a concurrent malignancy or malignancy within 3 years prior to Cycle 1 Day 1, with the exception of adequately treated basal or squamous cell carcinoma or curatively resected cervical cancer.
- •Patients with central nervous system (CNS) involvement
- •Patient has impairment of GI function or GI disease that may significantly alter the absorption of the study drugs
- •History of interstitial lung disease or pneumonitis.
- •Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
- •Patient is currently receiving any strong inducers or inhibitors of CYP3A4/5 and/or Substances that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5 and cannot be discontinued 7 days prior to Cycle 1 Day 1:
- •Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
- •History of retinal vein occlusion (RVO)
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Advanced or metastatic solid tumors
Patients in the Phase I portion of the study who have advanced or metastatic solid tumors
干预措施: ribociclib (Drug)
Advanced or metastatic solid tumors
Patients in the Phase I portion of the study who have advanced or metastatic solid tumors
干预措施: Trametinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Until progression of disease up to 1 year
Phase II part: The primary variable used to evaluate the efficacy of the ribociclib and trametinib combination is the ORR, defined as the proportion of patients with a best overall confirmed CR or PR, as assessed per RECIST 1.1 by investigator assessment.
Incidence of dose limiting toxicities (DLTs)
时间窗: 21-day cycle one of treatment
Phase Ib part: The primary variable is the incidence of DLTs during the first 21 days of therapy. Estimation of the MTD of the combination treatment will be based upon the estimation of the probability of DLT during the first 21 days of therapy for patients in the DDS.
次要结局
- Disease control rate(Until progression of disease up to 1 year)
- Progression disease rate(Until progression of disease up to 1 year)
- Progression free survival(Until progression of disease up to 1 year)
- Time to response(Until progression of disease up to 1 year)
- overall survival(Until death up to 1 year)
- Duration of response (DOR)(Until progression of disease up to 1 year)