Pre-emptive Cycline Treatment on Cetuximab-induced Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With an Intensified FOLFIRI.
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 25
- 试验地点
- 5
- 主要终点
- reduction of Grade > or = 2 acne-like skin rash by 30%
研究概览
简要总结
The aim of this study is to test the role of cycline in the prevention of acne-like skin rash in metastatic colorectal patients treated with Cetuximab and intensified FOLFIRI.
详细描述
Cetuximab, an Epidermal Growth Factor Receptor (EGFR) inhibitor, has shown to improve FOLFIRI efficacy up to 59.3% OR, in wild KRAS patients with advanced colorectal cancer. Skin toxicity occurs in 81.6% of patients as an acne-like skin rash developed on the face and the trunk inducing pain, decreasing quality of life and drug compliance. Over 104 patients enrolled in a phase II clinical trial sponsored by Center Paul Papin (NCT 00 559741), a grade > or = 2 cetuximab-acneiform rash occured in 51 patients (49%). In this trial Cetuximab was combined with a FOLFIRI intensified (5-FU intensification based on pharmacokinetics and pharmacogenetic studies of UGT1A1 status and DPD). Until now, no pre-emptive skin toxicity treatment with cycline has been demonstrated. Because of cycline's anti inflammatory properties and their use in inflammatory acne, cycline could prevent cetuximab-induced skin rash. In a randomized double-blind placebo-controlled phase III trial, Jatoi et al., failed to highlight any cycline effect on 61 patients. On the other hand, the STEPP study (95 pts) showed the impact of cycline to prevent panitumumab related skin toxicities. Our primary objective is to reduce the incidence of grade > or = 2 acne-like skin rash by 30% with a 6 weeks pre-emptive cycline treatment in patients with metastatic colorectal cancer undergoing cetuximab therapy.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced or metastatic colorectal cancer, histologically confirmed, first or second metastatic line
- •K-RAS wild-type
- •Adjuvant prior chemotherapy allowed provided that all toxicities are grade < or = 1 (excepted alopecia and neuropathy)
- •Age between 18 and 80 years
- •WHO Performance Status < or = 2
- •Complete initial assessment before first treatment administration for imaging and pharmacogenetic, within 15 days for biology, and within 7 days for clinical examination.
- •Haematologic and hepatic parameters : neutrophils > or = 1500 /mm3, platelets > or = 100000/mm3, Total bilirubin < or 2 x ULN, AST and ALT < or = 3 x ULN, APL < or = 5 x ULN
- •Absence of total dihydropyrimidine dehydrogenase deficiency
- •Patient able to comply with study requirements
- •Signed written informed consent
排除标准
- •History or presence of an other cancer, excepted cutaneous cancer (basocellular carcinoma), in situ cancer of the cervix or breast cancer curatively treated
- •Any other concomitant anti-cancer therapy
- •Prior anti EGFR therapy, anti angiogenic therapy is allowed
- •Prior cyclines hypersensitivity
- •Treatment with cyclines within 7 days before randomization
- •Presence of a rash at randomization time
- •Symptomatic or uncontrolled ventral nervous system metastases
- •Total dihydropyrimidine dehydrogenase deficiency
- •No recovery of any toxicity Grade < or = 1 related to a past anticancerous treatment excepted for alopecia and neuropathy
- •Active inflammatory bowel disease or other bowel
- •Significant serious pathology or any unstable medical condition (cardiac pathology uncontrolled, myocardial infarction within 6 months before enrollment, systemic active uncontrolled infection)
- •atropine contra-indication
- •any investigational agent without marketing authorization within 4 weeks before enrollment
- •Patient who is pregnant or breast feeding
- •Woman or man of childbearing potential not consenting to use adequate contraceptive precautions during the study
研究组 & 干预措施
Arm A
Intensified FOLFIRI plus Cetuximab + Doxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks + skin moisturizers (Dexeryl), sun protection.
干预措施: Doxycycline (Drug)
Arm A
Intensified FOLFIRI plus Cetuximab + Doxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks + skin moisturizers (Dexeryl), sun protection.
干预措施: Cetuximab (Drug)
Arm B
Intensified FOLFIRI plus Cetuximab + skin moisturizers (Dexeryl), sun protection.
干预措施: Cetuximab (Drug)
结局指标
主要结局
reduction of Grade > or = 2 acne-like skin rash by 30%
时间窗: 6 weeks of pre-emptive cycline treatment
Skin tolerance will be assessed by a dermatologist at each cycle and NCI CTCAE v4.0 will be use for grading. Skin standardized photographs will be done at every cycle and a central double blind review wil be planned. Time to first occurence of grade \> or =2 skin toxicity will be assessed, and specificity.
次要结局
- skin tolerance assessment(Until the end of Cetuximab treatment)
- Non skin toxicities assessment(Until the end of chemotherapy treatment)
- Biological correlation with response and survival(3 years)
- Time To Progression and Overall Survival(3 years)
- Resectability rate(Until the end of chemotherapy treatment)
- Efficacy Objective Response (OR) assessment(Until the end of chemotherapy treatment)