A Parallel Phase II Study With Irinotecan/Cetuximab (Until PD) Followed by XELOX/Cetuximab (Until PD) vs the Reverse Sequence in Metastatic CRC With Previous Benefit on Irinotecan/Bevacizumab Based Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 68
- 试验地点
- 10
- 主要终点
- Time To Progression
研究概览
简要总结
This phase II study will evaluate which is the best way to administer cetuximab after recurrence in 1st line irinotecan+bevacizumab based treatment and to obtain results of the efficacy of the oxaliplatin+cetuximab combination as 2nd line treatment.
详细描述
Because of the recent advances in the field of systemic chemotherapy for mCRC, like irinotecan, oxaliplatin, capecitabine, and targeted agents (Cetuximab, Bevacizumab) mCRC patients have an overall survival that in some cases reaches 25 months.Irinotecan is an inhibitor of the DNA enzyme topoisomerase I, with use in clinical practice for the last 10 years.In a phase II study with mCRC patients resistant to irinotecan based therapy the combination of irinotecan and Cetuximab (an IgG1 anti-EGFR antibody) yielded a response rate of 22.5%.Capecitabine was shown to have improved tolerability and response rate compared with bolus 5-FU, with comparable time to progression and survival.Oxaliplatin has been approved by the FDA for 2nd line treatment in the metastatic CRC setting as a number of trials have shown promising data for response rates, disease stabilization rates,median progression free survival (PFS) and overall survival (OS).KRAS is a predictive marker for clinical benefit from EGFR-based antibody treatment. KRAS is the first molecular marker for selection of a targeted therapy in combination with a standard chemotherapy regimen. Patients with KRAS wild-type tumors have a strong benefit from the administration of cetuximab with better PFS and objective responses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 72 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed locally advanced or metastatic colorectal cancer
- •Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)
- •ECOG performance status ≤ 2
- •Age 18 - 72 years
- •Patients who have had a CR, PR or SD after 1st line therapy based on Irinotecan+Bevacizumab
- •Paraffin block from the primary tumor in order to perform tha mutational analysis of the KRAS gene
- •Adequate liver (Bilirubin ≤ 1.5 upper normal limit, SGOT/SGPT ≤ 4 upper normal limit, ALP ≤ 2.5 upper normal limit),renal (Creatinine ≤ 1.5 upper normal limit) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥100,000/mm3) function
- •Patients must be able to understand the nature of this study
- •Written informed consent
排除标准
- •Presence of central nervous system or brain metastases
- •Pregnant or lactating woman
- •Life expectancy < 3 months
- •Previous radiotherapy within the last 4 weeks or > 25% of bone marrow or in the field where the treatment target is located
- •Peripheral neuropathy grade ≥2
- •Known hypersensitivity to Erbitux
- •Metastatic infiltration of the liver >50%
- •Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction or total colectomy
- •Active infection
- •Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer
- •Psychiatric illness or social situation that would preclude study compliance
研究组 & 干预措施
1
Irinotecan+Erbitux -> XELOX+Erbitux
干预措施: Irinotecan (Drug)
1
Irinotecan+Erbitux -> XELOX+Erbitux
干预措施: Capecitabine (Drug)
1
Irinotecan+Erbitux -> XELOX+Erbitux
干预措施: Cetuximab (Drug)
1
Irinotecan+Erbitux -> XELOX+Erbitux
干预措施: Oxaliplatin (Drug)
2
XELOX+Erbitux ->Irinotecan+Erbitux
干预措施: Irinotecan (Drug)
2
XELOX+Erbitux ->Irinotecan+Erbitux
干预措施: Capecitabine (Drug)
2
XELOX+Erbitux ->Irinotecan+Erbitux
干预措施: Cetuximab (Drug)
2
XELOX+Erbitux ->Irinotecan+Erbitux
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Time To Progression
时间窗: 1 year
次要结局
- Objective Response Rate(Objective responses confirmed by CT or MRI (on 3rd and 6th cycle))
- Toxicity profile(Toxicity assessment on each chemotherapy cycle)
- 1 year Survival and Overall Survival(Probability of 1-year survival (%))
- Correlation of the molecular characteristics of the tumor with the clinical outcome(Corralation after the end of chemotherapy)