Colorectal Cancer MetastaticSKINUXNCT01317433
Pre-emptive Cycline Treatment on Cetuximab Induced Skin Toxicity in Colorectal Cancer
A study testing Doxycycline and Cetuximab in people with Colorectal Cancer Metastatic and Skin Toxicity, run by Institut Cancerologie de l'Ouest at 5 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colorectal Cancer Metastatic, Skin Toxicity
- What is being tested?
- Doxycycline and Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 5 sitesFrance
- Study dates
- 29 Dec 2010to 10 Oct 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites
ICO Paul Papin
Angers, 49933
CHU Jean Minjoz
Besançon, 25000
CHU Morvan
Brest, 29609
Centre Hospitalier
Cholet, 49325
Centre Hospitalier Départemental Les Oudairies
La Roche-sur-Yon, 85925
About this study
Official title: 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.
Read the 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
- Being tested
- Doxycycline, Cetuximab
- Keywords
- Metastatic Colorectal Cancer, K-RAS wild-type, FOLFIRI, Cetuximab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
Doxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks.
CetuximabDrug
500 mg/m² IV infusion of 60 minutes every 15 days
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Doxycycline; Drug: Cetuximab |
| Arm B | Active comparator | Intensified FOLFIRI plus Cetuximab + skin moisturizers (Dexeryl), sun protection. Receives: Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks of pre-emptive cycline treatment
Secondary outcomes (6)
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.
Measured: Until the end of Cetuximab treatment
Non skin toxicities assessment
For non skin toxicities, only grade > or = 3 will be reported.
Measured: Until the end of chemotherapy treatment
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.
Measured: Until the end of chemotherapy treatment
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.
Measured: 3 years
Time To Progression and Overall Survival
Measured: 3 years
Resectability rate
Measured: Until the end of chemotherapy treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2011 (estimated)
- Study start29 Dec 2010
- Primary completion10 Oct 2016
- Study completion10 Oct 2016
Why it stopped: The study stopped due to a lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Cancerologie de l'Ouest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier Capitain, MD, PhD, Principal investigator, Institut Cancerologie de l'Ouest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01317433
- Sponsor's protocol ID
- CPP-450
- Other IDs
- 2010-019140-39
- Acronym
- SKINUX
- Status last verified
- Mar 2020
- First submitted
- 16 Mar 2011
- Last updated
- 25 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-emptive Cycline Treatment on Cetuximab-induced Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With an Intensified FOLFIRI.
- ClinicalTrials.gov ID
- NCT01317433
- Acronym / sponsor ID
- SKINUX / CPP-450
- Conditions
- Colorectal Cancer Metastatic, Skin Toxicity
- Keywords
- Metastatic Colorectal Cancer, K-RAS wild-type, FOLFIRI, Cetuximab
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study stopped due to a lack of recruitment
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Institut Cancerologie de l'OuestUniversity, hospital or other
- Study start
- 29 Dec 2010 (actual)
- Primary completion
- 10 Oct 2016 (actual)
- Study completion
- 10 Oct 2016 (actual)
- First posted
- 17 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Doxycycline, Drug: CetuximabIntensified FOLFIRI plus Cetuximab + Doxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks + skin moisturizers (Dexeryl), sun protection. |
| Arm B | Active comparator | Drug: CetuximabIntensified FOLFIRI plus Cetuximab + skin moisturizers (Dexeryl), sun protection. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DoxycyclineDoxycycline 100 mg daily per os to start 7 days before Cetuximab for 6 weeks. | Drug | Arm A |
| Cetuximab500 mg/m² IV infusion of 60 minutes every 15 days | Drug | Arm A, Arm B |
Primary outcome
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 secondary outcomes
skin tolerance assessment
Time frame: Until the end of Cetuximab treatment
Non skin toxicities assessment
Time frame: Until the end of chemotherapy treatment
Efficacy Objective Response (OR) assessment
Time frame: Until the end of chemotherapy treatment
Biological correlation with response and survival
Time frame: 3 years
Time To Progression and Overall Survival
Time frame: 3 years
Resectability rate
Time frame: Until the end of chemotherapy treatment
Results and safety
The study was stopped early (reason given: The study stopped due to a lack of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier Capitain, MD, PhD principal investigator
Institut Cancerologie de l'Ouest
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Doxycycline and Cetuximab in people with Colorectal Cancer Metastatic and Skin Toxicity, run by Institut Cancerologie de l'Ouest at 5 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The study stopped due to a lack of recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
reduction of Grade > or = 2 acne-like skin rash by 30% (time frame: 6 weeks of pre-emptive cycline treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2020.