Clinical trial NCT01317433: Pre-emptive Cycline Treatment on Cetuximab Induced Skin Toxicity in Colorectal Cancer
Official title: Pre-emptive Cycline Treatment on Cetuximab-induced Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With an Intensified FOLFIRI.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Colorectal Cancer Metastatic
Skin Toxicity
Keywords: Metastatic Colorectal Cancer
K-RAS wild-type
FOLFIRI
Cetuximab
Lead sponsor: Institut Cancerologie de l'Ouest
Sponsor class: OTHER
First posted: 2011-03-17
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: reduction of Grade > or = 2 acne-like skin rash by 30%
timeFrame: 6 weeks of pre-emptive cycline treatment
Secondary outcomes:
measure: skin tolerance assessment
timeFrame: Until the end of Cetuximab treatment
measure: Non skin toxicities assessment
timeFrame: Until the end of chemotherapy treatment
measure: Efficacy Objective Response (OR) assessment
timeFrame: Until the end of chemotherapy treatment
measure: Biological correlation with response and survival
timeFrame: 3 years
measure: Time To Progression and Overall Survival
timeFrame: 3 years
measure: Resectability rate
timeFrame: Until the end of chemotherapy treatment
Other outcomes:
Locations:
city: Angers
country: France
facility: ICO Paul Papin
city: Besançon
country: France
facility: CHU Jean Minjoz
city: Brest
country: France
facility: CHU Morvan
city: Cholet
country: France
facility: Centre Hospitalier
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Départemental Les Oudairies
Study officials:
affiliation: Institut Cancerologie de l'Ouest
name: Olivier Capitain, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: