Pre-emptive Cycline Treatment on Cetuximab Induced Skin Toxicity in Colorectal Cancer

NCT ID: NCT01317433

Last Updated: 2020-03-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-29
• Study Completion Date: 2016-10-10

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.

Conditions

Colorectal Cancer Metastatic; Skin Toxicity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Doxycycline

Intervention Type: DRUG

Doxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks.

Cetuximab

Intervention Type: DRUG

500 mg/m² IV infusion of 60 minutes every 15 days

Arm B

Intensified FOLFIRI plus Cetuximab + skin moisturizers (Dexeryl), sun protection.

Group Type: ACTIVE_COMPARATOR

Cetuximab

Intervention Type: DRUG

500 mg/m² IV infusion of 60 minutes every 15 days

Interventions

Doxycycline

Doxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks.

Intervention Type: DRUG

Cetuximab

500 mg/m² IV infusion of 60 minutes every 15 days

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut Cancerologie de l'Ouest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olivier Capitain, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institut Cancerologie de l'Ouest

Locations

ICO Paul Papin

Angers, , France

CHU Jean Minjoz

Besançon, , France

CHU Morvan

Brest, , France

Centre Hospitalier

Cholet, , France

Centre Hospitalier Départemental Les Oudairies

La Roche-sur-Yon, , France

Countries

France

Related Links

https://www.centrepaulpapin.org/

Sponsor Information

Other Identifiers

2010-019140-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CPP-450

Identifier Type: -

Identifier Source: org_study_id