Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With Anti-EGFR and Chemotherapy (DERMIA)

Study Overview
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Brief Summary
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Clinical evidence has suggested that sub-antimicrobial doses of doxycycline may have the potential to treat inflammatory lesions of acne. The efficacy of doses below 100 mg/day of doxycycline in the prevention of skin toxicity in patients with treated with Epidermal Growth Factor Receptor (EGFR)-targeted therapies has never been studied. Therefore, the aim of the present study is to describe the efficacy of doxycycline 50 or 100 mg per day in the prevention of skin toxicity in patients with metastatic Colorectal cancer (mCRC) treated with anti-EGFR in combination with chemotherapy.

Official Title
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Phase II Clinical Trial of Doxycycline 50 mg or 100 mg Daily for the Prevention of Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With Anti-EGFR and Chemotherapy

Conditions
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Skin Toxicity

Intervention / Treatment
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* Drug: Doxycycline 50Mg Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man or woman at least 18 years old Capable of understanding, signing and dating an informed consent approved by an Independent Ethics Committee (IEC) Histologically confirmed adenocarcinoma of the colon or rectum in patients with initially unresectable metastatic (M1) disease Wild-type RAS tumour status confirmed before study inclusion at local institution Patients who have a treatment plan based on FOLFOX + anti-EGFR or FOLFIRI + anti-EGFR, as first-line treatment of mCRC Eastern Cooperative Oncology Group (ECOG) performance status ≤2 Adequate bone marrow function: neutrophils ≥1.5 x109/L; platelets ≥100 x109/L; haemoglobin ≥9 g/dL Hepatic, renal and metabolic function as follows: Total bilirubin count ≤1.5 x upper limit of normal (ULN), Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) <5 x ULN; Renal function, calculated as creatinine clearance or 24-hour creatinine clearance ≥50 mL/min; Magnesium > lower limit of normal (LLN) Exclusion Criteria: History of prior or concurrent central nervous system (CNS) metastases History of another primary cancer, except: curatively treated in situ cervical cancer, or curatively resected non-melanoma skin cancer, or other primary solid tumour curatively treated with no known active disease present and no treatment administered for ≥5 years before treatment initiation Known hypersensitivity to tetracyclines Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma Prior adjuvant chemotherapy for colorectal cancer terminated less than 6 months before metastatic disease was diagnosed Unresolved toxicities of a previous systemic treatment that, in the opinion of the investigator, cause the patient unfit for inclusion Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab), antivascular endothelial growth factor (VEGF) or treatment with small molecule EGFR inhibitors (e.g., erlotinib) Prior hormonal therapy, immunotherapy or approved or experimental antibody/proteins ≤30 days before inclusion. Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computed tomography (CT) Treatment for systemic infection within 14 days before the start of study treatment Acute or subacute intestinal occlusion and/or active inflammatory bowel disease or other bowel disease that causes chronic diarrhoea (defined as grade ≥ 2 diarrhoea according to Common Terminology Criteria for Adverse Events (CTCAE) Clinically significant peripheral sensory neuropathy Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment History of Gilbert disease or known dihydropyrimidine deficiency syndrome Recent gastroduodenal ulcer to be active or uncontrolled Recent pulmonary embolism, deep vein thrombosis, or other significant venous event Pre-existing bleeding diathesis and/or coagulopathy with exception of well-controlled anticoagulation therapy Recent major surgical procedure, open biopsy, or significant traumatic injury not yet recovered from prior major surgery History of any disease that may increase the risks associated with study participation or may interfere with the interpretation of study results. Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection Any disorder that compromises the patient's ability to provide written informed consent and/or comply with study procedures Any investigational agent within 30 days prior to inclusion Pregnant or breastfeeding woman Surgery (excluding diagnostic biopsy or placement of a central venous catheter) and/or radiotherapy within 28 days prior to inclusion in the study. Male or female of childbearing age who do not agree with taking adequate contraceptive precautions, i.e. use contraception double barrier (e.g. diaphragm plus condoms) or abstinence during the course of the study and for 6 months after the last administration of study drug for women and 1 month for men The patient is unwilling or unable to meet the requirements of the study. Psychological, geographical, familial or sociological conditions that potentially prevent compliance with the study protocol and follow-up schedule. These conditions should be discussed with the patient before inclusion in the trial.

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: Doxycycline<br>Doxycycline 50 mg p.o. daily during 6 weeks | Drug: Doxycycline 50Mg Tablet<br>* Doxycycline administered p.o once daily at a 50 mg dose for 6 weeks beginning on Day -1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy in the prevention of skin toxicity | Monitoring of skin toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events | During 6-week skin treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life of patients during the treatment | Change in Dermatology Life Quality Index (DLQI) score | Up to 7 weeks | 
| Incidence of Treatment-Emergent Adverse Events | Number of adverse events per patient | Up to 6 weeks |