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

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

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.

Study Overview

• Status: Completed
• Conditions: Skin Toxicity
• Intervention / Treatment: Drug: Doxycycline 50Mg Tablet

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Algeciras, Spain
    • Hospital Punta Europa
  • Cadiz, Spain
    • Hospital Puerta del Mar
  • Cadiz, Spain
    • Hospital Puerto Real
  • Cáceres, Spain
    • Hospital San Pedro de Alcantara
  • Granada, Spain
    • Hospital Clínico San Cecilio
  • Huelva, Spain
    • Hospital Juan Ramón Jimenez
  • Jerez De La Frontera, Spain
    • Hospital de Jerez
  • Sevilla, Spain
    • Hospital Virgen Macarena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxycycline; Doxycycline 50 mg p.o. daily during 6 weeks	Drug: Doxycycline 50Mg Tablet; Doxycycline administered p.o once daily at a 50 mg dose for 6 weeks beginning on Day -1

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundacion CRIS de Investigación para Vencer el Cáncer
• Collaborators: Apices Soluciones S.L.; Amgen
• Investigators: Principal Investigator: Patricia Ramirez-Daffós, MD, Hospital Universitario Puerta del Mar

Publications and helpful links

General Publications

• Ramirez-Daffos P, Jimenez-Orozco E, Bolanos M, Gonzalez Astorga B, Rubiales S, Ceballos-Barbancho E, Rodriguez Garcia JM, Reina JJ. A phase 2 study for evaluating doxycycline 50 mg once daily and 100 mg once daily as preemptive treatment for skin toxicity in patients with metastatic colorectal cancer treated with an anti-EGFR and chemotherapy. Support Care Cancer. 2022 Oct;30(10):8081-8088. doi: 10.1007/s00520-022-07254-5. Epub 2022 Jul 1.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2018
• Primary Completion (Actual): April 6, 2020
• Study Completion (Actual): April 6, 2020

Study Registration Dates

• First Submitted: February 19, 2018
• First Submitted That Met QC Criteria: February 27, 2018
• First Posted (Actual): February 28, 2018

Study Record Updates

• Last Update Posted (Actual): April 8, 2020
• Last Update Submitted That Met QC Criteria: April 7, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: DERMIA; 2017-004413-98 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No