A Multicenter, Open-Label, Randomized, Phase 2 Study to Evaluate the Efficacy and Safety of NKTR-102 Versus Irinotecan in Patients With Second-Line, Irinotecan-Naive, KRAS-Mutant, Metastatic Colorectal Cancer (mCRC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 22
- 主要终点
- Kaplan-Meier Estimate of PFS by Central Radiological Review: ITT Population
研究概览
简要总结
This study will evaluate whether NKTR-102, an investigational drug has an anti-tumor effect in patients with colorectal cancer. This study will also evaluate how the safety and anti-tumor activity of NKTR-102 compares with irinotecan, a cancer drug that is approved for use in the US for treatment of patients with certain types of colorectal cancer.
详细描述
NKTR-102 (Topoisomerase I Inhibitor Polymer Conjugate) is a polyethylene glycol (PEG) conjugate of irinotecan. Irinotecan is a topoisomerase I inhibitor approved worldwide. In the US, irinotecan is indicated as a component of first-line therapy in combination with 5 fluorouracil (5 FU) and leucovorin for patients with metastatic carcinoma of the colon or rectum. Irinotecan is also indicated for patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy.
Second-line therapy for colorectal cancer typically involves cetuximab and irinotecan. However, growing evidence indicates that cetuximab (or other EGFR inhibitors) is not appropriate therapy for patients with mutant KRAS. For these patients, irinotecan may be appropriate as a single agent, and a new therapy that could improve upon efficacy and safety would provide an important option for the treatment of advanced colorectal cancer.
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
- •metastatic colorectal cancer
- •tumor with k-ras mutation
排除标准
- •More than 1 prior regimen for treatment of metastatic disease
研究组 & 干预措施
irinotecan
irinotecan IV every 3 weeks
干预措施: irinotecan (Drug)
NKTR-102
NKTR-102 IV every 3 weeks
干预措施: NKTR-102 (Drug)
结局指标
主要结局
Kaplan-Meier Estimate of PFS by Central Radiological Review: ITT Population
时间窗: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study, approximately 42 months.
PFS was defined as the time from the date of randomisation to the date of disease progression (assessed by central radiological review according to Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) or death due to any cause, whichever comes first. PFS was determined using the intention-to-treat (ITT) population which included all randomized patients who underwent baseline evaluation, with treatment assigned according to randomized arm. For patients whose disease did not progress or who did not die, the PFS time was censored at the time of the last tumor assessment that demonstrated lack of disease progression. For patients who received new anti-cancer therapy, the PFS time was censored at the time of last tumor assessment prior to the new anti-cancer therapy starts.
次要结局
- Kaplan-Meier Estimate of OS: ITT Population(From randomization to death, loss to follow-up, withdrawal of consent for further follow-up for survival, or end of study, approximately 42 months.)
- DoR by Central Radiological Review: ITT Population(From the time measurement criteria for CR/PR (whichever was first recorded) were first met until the first date that recurrent disease or PD or death was objectively documented, assessed until the end of study approximately 42 months)
- ORR by Central Radiological Review: ITT Population(From randomization of the first subject until documented disease progression, start of new therapy for cancer, death, or end of study approximately 42 months)
- Percentage of Participants (≥2%) With Treatment-Emergent Adverse Events NCI-CTCAE Grade 3 or Higher(From the first dose of study medication through the End-of-Treatment visit (30 ± 3 days from last dose of study drug), assessed until the end of study approximately 42 months)
- PK Parameters of NKTR-102 or Irinotecan and Respective Metabolites(Days 1, 2, 3, 4, 8 and 15 of Cycles 1 and 3 and Day 1 of Cycles 2, 4 and all subsequent cycles, until End of Study, approximately 42 months.)