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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2012 by ICO Paul Papin
Sponsor:
Information provided by (Responsible Party):
ICO Paul Papin
ClinicalTrials.gov Identifier:
NCT01317433
First received: March 16, 2011
Last updated: February 28, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer Metastatic
Skin Toxicity
Drug: Doxycycline
Drug: Cetuximab
Phase 3

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by ICO Paul Papin:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 130
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)
Arms Assigned Interventions
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
No Intervention: Arm B
Intensified FOLFIRI plus Cetuximab + skin moisturizers (Dexeryl), sun protection.
Drug: Cetuximab
500 mg/m² IV infusion of 60 minutes every 15 days

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01317433

Contacts
Contact: Virginie Berger, MD, PhD 33 2 41 35 27 34 virginie.berger@ico.unicancer.fr
Contact: Jessy Delaye, M Sc 33 2 41 35 29 31 jessy.delaye@ico.unicancer.fr

Locations
France
ICO Paul Papin Recruiting
Angers, France, 49933
Contact: Virginie Berger, MD, PhD       virginie.berger@ico.unicancer.fr   
Principal Investigator: Olivier Capitain, MD, PhD         
CHU Jean Minjoz Not yet recruiting
Besançon, France, 25000
Contact: Christophe Borg, MD       christophe.borg@efs.sante.fr   
Principal Investigator: Christophe Borg, MD         
CHU Morvan Recruiting
Brest, France, 29609
Contact: Jean-Philippe Metges, MD       jean-philippe.metges@chu-brest.fr   
Principal Investigator: Jean-Philippe Metges, MD         
Centre Hospitalier Recruiting
Cholet, France, 49325
Contact: You Heng Lam, MD       you.lam@ch-cholet.fr   
Principal Investigator: You Heng Lam, MD         
Centre Hospitalier Départemental Les Oudairies Recruiting
La Roche Sur Yon, France, 85925
Contact: Roger Faroux, MD       roger.faroux@chd-vendee.fr   
Principal Investigator: Roger Faroux, MD         
Sponsors and Collaborators
ICO Paul Papin
Investigators
Principal Investigator: Olivier Capitain, MD, PhD ICO Paul Papin
  More Information

No publications provided

Responsible Party: ICO Paul Papin
ClinicalTrials.gov Identifier: NCT01317433     History of Changes
Other Study ID Numbers: CPP-450, 2010-019140-39
Study First Received: March 16, 2011
Last Updated: February 28, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by ICO Paul Papin:
Metastatic Colorectal Cancer
K-RAS wild-type
FOLFIRI
Cetuximab

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Cetuximab
Doxycycline
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014