Efficacy and Safety of the Prophylactic Use of Doxycycline +/- Vitamin K Cream

Study Overview
=================
Brief Summary
-----------------
The aim of this Phase 2, two-arm, randomized, double blind placebo controlled study is to evaluate the efficacy of combination therapy of doxycycline and Vitamin K1 compared to doxycycline plus placebo for the prevention of acne-like skin rash in mCRC patients receiving first line cetuximab treatment.

Detailed Description
-----------------
The aim of this Phase 2, two-arm, randomized, double blind placebo controlled study is to evaluate the efficacy of combination therapy of doxycycline and Vitamin K1 compared to doxycycline plus placebo for the prevention of acne-like skin rash in mCRC patients receiving first line cetuximab treatment.

Official Title
-----------------
A Double Blind Placebo Controlled Randomized Phase II Study Evaluating the Efficacy and Safety of the Prophylactic Use of Doxycycline +/- Vitamin K Cream in First Line mCRC Patients Treated With Erbitux and FOLFIRI.

Conditions
-----------------
Metastatic Colorectal Cancer

Intervention / Treatment
-----------------
* Device: Reconval K1 Cream
* Device: Reconval Cream


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent must be given Patient ≥ 18 years Histologically proven and measurable metastatic adenocarcinoma of the colon or rectum (according to modified RECIST criteria v.1.1) Patients eligible for Erbitux and FOLFIRI treatment K-Ras wild type tumour Metastatic disease Life expectancy of at least 12 weeks WHO performance status of 0 or 1 Effective contraception for both male and female patients if the risk of conception exists Adequate organ function Adequate bone marrow, hepatic and renal function (Hemoglobin > 10.0 g/dL, platelet count > 100 x 109/L, absolute neutrophil count > 1.5 x 109/L; ALAT, ASAT < 2.5 x ULN (upper limit of normal range) or < 5x ULN in case of liver metastasis; Alkaline phosphatase < 2.5 x ULN; Total bilirubin < 1.5 x ULN; Creatinine clearance > 50 mL/min (calculated according to Cockcroft and Gault formula)). Exclusion Criteria: Prior treatment for metastatic disease (adjuvant therapy with 5-FU/oxaliplatin based regimens) allowed if stopped 6 months prior to registration on study Prior treatment with EGFR inhibitor Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment with study drugs Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy or hormone therapy not indicated in the study protocol Any active dermatological condition > grade 1 at baseline possibly interfering with or influencing the results or conduct of the present study Brain metastasis (known or suspected) Significant impairment of intestinal resorption (e.g. chronic diarrhea, inflammatory bowel disease) Any other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias) Known allergy or any other adverse reaction to any of the study drugs or to any related compound. Any organ allograft requiring immunosuppressive therapy. Pregnancy (absence to be confirmed by serum/urine beta human chorion gonadotrophin (HCG)) or breast-feeding. Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix surgically cured or adequately treated. Known drug abuse / alcohol abuse Legal incapacity or limited legal capacity Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and followup schedule; those conditions should be discussed with the patient before registration in the trial. Medical or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or meaningfully sign informed consent. Known M. Meulengracht (Gilbert´s disease) or DPD-insufficiency Known coagulation disorders Ongoing or planned treatment with coumarin derivates

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Phase II trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metastatic colorectal cancer, Doxycycline, Vitamin K1 Cream<br> | Device: Reconval K1 Cream<br> <br> |
| Placebo Comparator: Metastatic colorectal cancer, Doxycycline, Cream<br> | Device: Reconval Cream<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of acne-like skin rash grade ≥ 2 (according to the CTCAE) version 4.02) during the 8 weeks of skin treatment. |  | Week 8 | 
| PFS rate, toxicity, compliance |  | Week 8 |