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

NCT01317433 | Terminated DMC

• 2 other identifiers: CPP-4502010-019140-39
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 5

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.

Conditions

Colorectal Cancer Metastatic; Skin Toxicity

Keywords

Metastatic Colorectal Cancer; K-RAS wild-type; FOLFIRI; Cetuximab

Outcome Measures

Primary Outcomes (1)

• reduction of Grade > or = 2 acne-like skin rash by 30%

  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 Outcomes (6)

• skin tolerance assessment

  Until the end of Cetuximab treatment

• Non skin toxicities assessment

  Until the end of chemotherapy treatment

• Efficacy Objective Response (OR) assessment

  Until the end of chemotherapy treatment

• Biological correlation with response and survival

  3 years

• Time To Progression and Overall Survival

  3 years

Study Arms (2)

Arm A

EXPERIMENTAL

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; Drug: Cetuximab

Arm B

ACTIVE COMPARATOR

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

Drug: Cetuximab

Interventions

Doxycycline DRUG

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

Arm A

Cetuximab DRUG

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

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead

Study Sites (5)

ICO Paul Papin

Angers, 49933, France

Location

CHU Jean Minjoz

Besançon, 25000, France

Location

CHU Morvan

Brest, 29609, France

Location

Centre Hospitalier

Cholet, 49325, France

Location

Centre Hospitalier Départemental Les Oudairies

La Roche-sur-Yon, 85925, France

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Doxycycline; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Olivier Capitain, MD, PhD

  Institut Cancerologie de l'Ouest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2011
• First Posted: March 17, 2011
• Study Start: December 29, 2010
• Primary Completion: October 10, 2016
• Study Completion: October 10, 2016
• Last Updated: March 25, 2020

Record last verified: 2020-03

Locations

FR (5)