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

March 23, 2020 updated by: Institut Cancerologie de l'Ouest

Pre-emptive Cycline Treatment on Cetuximab-induced Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With an Intensified FOLFIRI.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49933
        • ICO Paul Papin
      • Besançon, France, 25000
        • Chu Jean Minjoz
      • Brest, France, 29609
        • CHU Morvan
      • Cholet, France, 49325
        • Centre Hospitalier
      • La Roche Sur Yon, France, 85925
        • Centre Hospitalier Departemental Les Oudairies

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Doxycycline
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
Active Comparator: Arm B
Intensified FOLFIRI plus Cetuximab + skin moisturizers (Dexeryl), sun protection.
Drug: Cetuximab
500 mg/m² IV infusion of 60 minutes every 15 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
reduction of Grade > or = 2 acne-like skin rash by 30%
Time Frame: 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.
6 weeks of pre-emptive cycline treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
skin tolerance assessment
Time Frame: Until the end of Cetuximab treatment
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.
Until the end of Cetuximab treatment
Non skin toxicities assessment
Time Frame: Until the end of chemotherapy treatment
For non skin toxicities, only grade > or = 3 will be reported.
Until the end of chemotherapy treatment
Efficacy Objective Response (OR) assessment
Time Frame: Until the end of chemotherapy treatment
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.
Until the end of chemotherapy treatment
Biological correlation with response and survival
Time Frame: 3 years
Biological correlation with response and survival will be tested for KRAS, BRAF, PI3K,PTEN, epiregulin, amphiregulin, IGF1, Syndecan-1, UBE2C, EGFR polymorphism.
3 years
Time To Progression and Overall Survival
Time Frame: 3 years
3 years
Resectability rate
Time Frame: Until the end of chemotherapy treatment
Until the end of chemotherapy treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Cancerologie de l'Ouest

Investigators

  • Principal Investigator: Olivier Capitain, MD, PhD, Institut Cancerologie de l'Ouest

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 29, 2010

Primary Completion (Actual)

October 10, 2016

Study Completion (Actual)

October 10, 2016

Study Registration Dates

First Submitted

March 16, 2011

First Submitted That Met QC Criteria

March 16, 2011

First Posted (Estimate)

March 17, 2011

Study Record Updates

Last Update Posted (Actual)

March 25, 2020

Last Update Submitted That Met QC Criteria

March 23, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CPP-450
  • 2010-019140-39 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Colorectal Cancer Metastatic

Clinical Trials on Doxycycline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Greece

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe