Pre-emptive Cycline Treatment on Cetuximab Induced Skin Toxicity in Colorectal Cancer (SKINUX)
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.
Colorectal Cancer Metastatic
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pre-emptive Cycline Treatment on Cetuximab-induced Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With an Intensified FOLFIRI.|
- reduction of Grade > or = 2 acne-like skin rash by 30% [ Time Frame: 6 weeks of pre-emptive cycline treatment ] [ Designated as safety issue: No ]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.
- skin tolerance assessment [ Time Frame: Until the end of Cetuximab treatment ] [ Designated as safety issue: Yes ]Skin tolerance will be assessed weekly by a dermatologist from C1 to C3, and biweekly from C4 to C6 and NCI CTCAE v4.0 will be use for grading. All grade > or = 1 skin and hair/nails toxicities will be reported. Time to most severe skin toxicity will be assessed. Quality of life questionnaires with a skin interest (DLQI) will be evaluated at baseline and at each cycle.
- Non skin toxicities assessment [ Time Frame: Until the end of chemotherapy treatment ] [ Designated as safety issue: Yes ]For non skin toxicities, only grade > or = 3 will be reported.
- Efficacy Objective Response (OR) assessment [ Time Frame: Until the end of chemotherapy treatment ] [ Designated as safety issue: No ]Efficacy OR (Complete Response + Partial Response) will be assessed by the investigator with usual tumoral evaluation. Tumoral evaluation will be assessed with the same exam throughout the trial.
- Biological correlation with response and survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]Biological correlation with response and survival will be tested for KRAS, BRAF, PI3K,PTEN, epiregulin, amphiregulin, IGF1, Syndecan-1, UBE2C, EGFR polymorphism.
- Time To Progression and Overall Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Resectability rate [ Time Frame: Until the end of chemotherapy treatment ] [ Designated as safety issue: No ]
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||November 2015|
|Estimated Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: 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.
Doxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks.Drug: Cetuximab
500 mg/m² IV infusion of 60 minutes every 15 days
No Intervention: Arm B
Intensified FOLFIRI plus Cetuximab + skin moisturizers (Dexeryl), sun protection.
500 mg/m² IV infusion of 60 minutes every 15 days
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.
|Contact: Virginie Berger, MD, PhD||33 2 41 35 27 firstname.lastname@example.org|
|Contact: Jessy Delaye, M Sc||33 2 41 35 29 email@example.com|
|ICO Paul Papin||Recruiting|
|Angers, France, 49933|
|Contact: Virginie Berger, MD, PhD firstname.lastname@example.org|
|Principal Investigator: Olivier Capitain, MD, PhD|
|CHU Jean Minjoz||Not yet recruiting|
|Besançon, France, 25000|
|Contact: Christophe Borg, MD email@example.com|
|Principal Investigator: Christophe Borg, MD|
|Brest, France, 29609|
|Contact: Jean-Philippe Metges, MD firstname.lastname@example.org|
|Principal Investigator: Jean-Philippe Metges, MD|
|Cholet, France, 49325|
|Contact: You Heng Lam, MD email@example.com|
|Principal Investigator: You Heng Lam, MD|
|Centre Hospitalier Départemental Les Oudairies||Recruiting|
|La Roche Sur Yon, France, 85925|
|Contact: Roger Faroux, MD firstname.lastname@example.org|
|Principal Investigator: Roger Faroux, MD|
|Principal Investigator:||Olivier Capitain, MD, PhD||ICO Paul Papin|