FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema

Study Overview
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Brief Summary
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The purpose of this interventional study is to assess the progression free survival (one year) of patients with treatment of FOLFIRI and cetuximab, combined with an optional dermal prophylaxis. Further Objectives: Development of acneiforme follicular exanthema >= grade 2 Duration until development of acneiforme follicular exanthema >= grade 2 Development of paronychia Development skin fissure (hand and foot) Objective remission according RECIST 1.1 Rate of secondary resections of liver metastasis with a curative approach Assessment of safety and tolerability Overall survival Progression free survival

Detailed Description
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Subjects with metastatic colorectal cancer and confirmed KRAS-wildtype status in 1st line therapy will be included in this phase IV-study. Subject will receive a regimen of FOLFIRI in combination with Cetuximab every two weeks during study treatment phase. Treatment continues until disease progression complete response development of status of operability an uncontrollable exanthema grade 3 or 4 or intolerable toxicity is diagnosed. After study discontinuation or end of treatment, respectively, patients will be followed up until the the last patient was treated for 12 months and has completed the 36-months follow up phase. Tumor response will be evaluated (according to RECIST 1.1) every 12 weeks and at the end of study treatment

Official Title
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Non-randomized Phase-IV-study to Investigate the Efficacy of FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema

Conditions
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Colorectal Cancer Metastatic

Intervention / Treatment
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* Drug: FOLFIRI + Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed metastatic colorectal cancer (primary tumor or metastasis) Confirmation of KRAS wildtype status Confirmation of EGFR-Expression in the tumor Stadium IV Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Qualified for an application of FOLFIRI + Cetuximab treatment Signed patient informed consent form Of either gender and aged 18 years or more Estimated lifespan more than 3 months Measurable disease according to RECIST 1.1 guidelines. The evaluation has to be max. 4 weeks Effective and adequate contraceptive precautions of man or woman in a childbearing potential age (double barrier method) Leucocytes ≥ 3,0 x 10^9/L with neutrophils ≥ 1,5 x 10^9/L, thrombocytes ≥ 100 x 10^9/L, haemoglobin ≥ 5,6 mmol/L Serum bilirubin ≤ 1,5 x ULN (upper limit of normal) ALAT and ASAT ≤ 2,5 x ULN; if metastasis in liver, than ALAT and ASAT ≤ 5 x ULN Serum creatinin ≤ 1,5 x ULN If applicable a prior operation has to be min. 4 weeks ago, biopsy more than 1 week until initiation of treatment. Wounds of operations had to be completely cured No toxicity of prior treatments Exclusion Criteria: KRAS-gene mutation Confirmation of non-EGFR-Expression Prior treatment with an EGRF-receptor inhibitor Prior chemotherapy of the mCRC, except (neo-)adjuvant therapy, which had to be ended min. 6 months before recruitment Experimental treatment medication within 30 days before recruitment Known hypersensitivity against components of the chemotherapy, cetuximab, doxycycline, Reconval K1 or Dermatop Rosacea Other chronic dermal diseases with development of papula or pustule Known lung fibrosis or interstitial pneumonitis or interstitial lung diseases keratitis, ulcerative keratitis or severe form of dry eye Pregnancy or breast feeding Brain metastasis Clinical relevant coronary heart disease, myocardial infarction within the last 12 months or high risk of uncontrollable arrhythmia Acute or subacute ileus or chronic colon-inflammation or chronic diarrhea Symptomatic peritoneal carcinomatosis Serious, non-healing wounds, ulcera or bone fractures Uncontrollable arterial hypertension Therapeutic anticoagulation (e.g. therapy with marcumar) Known dihydropyrimidine dehydrogenase deficiency Gilbert-Meulengracht-syndrome Other malignant tumours less than five years old. Exceptions include basocellular carcinoma or an in situ cancer of the cervix uteri if they are curative treated as well as an untreated, locally confined, asymptotic low risk (indolent) prostata carcinoma (Stage T ≤ T1-2a, PSA < 15 ng/ml, Gleason-Score ≤ 6 ). Known abuse of narcotic drugs or alcohol Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures Any significant concomitant disease that excludes the participation to the study Missing or limited juristic contractual capability

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FOLFIRI + Cetuximab<br> | Drug: FOLFIRI + Cetuximab<br>* Cetuximab (Erbitux® )- Cetuximab is a recombinant IgG1 chimeric monoclonal antibody directed against human epidermal growth factor receptor (EGFR). FOLFIRI regimen Administration Schedule: Cetuximab at a initial dose 400 mg/sqm (first week), then 250 mg/sqm on day 1 and 8 Background Chemotherapy (every two weeks) Irinotecan 180 mg/m² iv , 90 min on day 1 Folic acid (racemic) 400 mg/m², 120 min on day 1 5-FU 400 mg/m² bolus on day 1 5-FU 2400 mg/m² iv over 46 h on day 1 to 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival rate at 12 months | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | up to end of follow-up-phase (36 months) | 
| ORR | Objective response rate over the entire treatment period | approximately 12 months | 
| OS | Overall survival time | The time from regsitration date to the date of death | 
| Duration until development of acneiforme follicular exanthema >= grade 2 | Duration until development of acneiforme follicular exanthema >= grade 2 during treatment-phase | approximately 12 months | 
| Development of paronychia | Development of paronychia during treatment-phase | approximately 12 months | 
| Development of skin fissure (hand and foot) | Development of skin fissure (hand and foot) during treatment-phase | approximately 12 months | 
| Rate of secondary resections of metastasis of liver with a curative approach | Rate of secondary resections of metastasis of liver with a curative approach during treatment-phase | approximately 12 months | 
| Assessment of safety and tolerability | Assessment of safety and tolerability during treatment phase | approximately 12 months | 
| Development of acneiforme follicular exanthema >= grade2 | Development of acneiforme follicular exanthema >= grade2 during treatment phase | approximately 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase IV Study, Metastatic Colorectal Cancer (mCRC, Cetuximab (Erbitux), first-line treatment, acneiform follicular exanthema, rash, vitamin K1