Back to resultsPre-emptive Cycline Treatment on Cetuximab Induced Skin Toxicity in Colorectal Cancer (SKINUX)
Primary Purpose
Colorectal Cancer Metastatic, Skin Toxicity
Status
Terminated
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Doxycycline
Cetuximab
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring Metastatic Colorectal Cancer, K-RAS wild-type, FOLFIRI, Cetuximab
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
Sites / Locations
- ICO Paul Papin
- CHU Jean Minjoz
- CHU Morvan
- Centre Hospitalier
- Centre Hospitalier Départemental Les Oudairies
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A
Arm B
Arm Description
Intensified FOLFIRI plus Cetuximab + Doxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks + skin moisturizers (Dexeryl), sun protection.
Intensified FOLFIRI plus Cetuximab + skin moisturizers (Dexeryl), sun protection.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
skin tolerance assessment
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
For non skin toxicities, only grade > or = 3 will be reported.
Efficacy Objective Response (OR) assessment
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
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
Resectability rate
Full Information
NCT ID
NCT01317433
First Posted
March 16, 2011
Last Updated
March 23, 2020
Sponsor
Institut Cancerologie de l'Ouest
1. Study Identification
Unique Protocol Identification Number
NCT01317433
Brief Title
Pre-emptive Cycline Treatment on Cetuximab Induced Skin Toxicity in Colorectal Cancer
Acronym
SKINUX
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
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Terminated
Why Stopped
The study stopped due to a lack of recruitment
Study Start Date
December 29, 2010 (Actual)
Primary Completion Date
October 10, 2016 (Actual)
Study Completion Date
October 10, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Cancerologie de l'Ouest
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Metastatic, Skin Toxicity
Keywords
Metastatic Colorectal Cancer, K-RAS wild-type, FOLFIRI, Cetuximab
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
Intensified FOLFIRI plus Cetuximab + Doxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks + skin moisturizers (Dexeryl), sun protection.
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Intensified FOLFIRI plus Cetuximab + skin moisturizers (Dexeryl), sun protection.
Intervention Type
Drug
Intervention Name(s)
Doxycycline
Intervention Description
Doxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Intervention Description
500 mg/m² IV infusion of 60 minutes every 15 days
Primary Outcome Measure Information:
Title
reduction of Grade > or = 2 acne-like skin rash by 30%
Description
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.
Time Frame
6 weeks of pre-emptive cycline treatment
Secondary Outcome Measure Information:
Title
skin tolerance assessment
Description
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.
Time Frame
Until the end of Cetuximab treatment
Title
Non skin toxicities assessment
Description
For non skin toxicities, only grade > or = 3 will be reported.
Time Frame
Until the end of chemotherapy treatment
Title
Efficacy Objective Response (OR) assessment
Description
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.
Time Frame
Until the end of chemotherapy treatment
Title
Biological correlation with response and survival
Description
Biological correlation with response and survival will be tested for KRAS, BRAF, PI3K,PTEN, epiregulin, amphiregulin, IGF1, Syndecan-1, UBE2C, EGFR polymorphism.
Time Frame
3 years
Title
Time To Progression and Overall Survival
Time Frame
3 years
Title
Resectability rate
Time Frame
Until the end of chemotherapy treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Capitain, MD, PhD
Organizational Affiliation
Institut Cancerologie de l'Ouest
Official's Role
Principal Investigator
Facility Information:
Facility Name
ICO Paul Papin
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
CHU Jean Minjoz
City
Besançon
ZIP/Postal Code
25000
Country
France
Facility Name
CHU Morvan
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
Centre Hospitalier
City
Cholet
ZIP/Postal Code
49325
Country
France
Facility Name
Centre Hospitalier Départemental Les Oudairies
City
La Roche Sur Yon
ZIP/Postal Code
85925
Country
France
12. IPD Sharing Statement
Links:
URL
https://www.centrepaulpapin.org/
Description
Sponsor Information
Learn more about this trial
Pre-emptive Cycline Treatment on Cetuximab Induced Skin Toxicity in Colorectal Cancer
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