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

Skin Toxicity Clinical Trial

— DERMIA  

Official title:

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 Trial Details — Status: Completed

Administrative data

• NCT number: NCT03448731
• Other study ID #: DERMIA
• Secondary ID: 2017-004413-98
• Status: Completed
• Phase: Phase 2
• Start date: May 10, 2018
• Est. completion date: April 6, 2020

Study information

• Verified date: April 2020
• Source: Fundacion CRIS de Investigación para Vencer el Cáncer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: April 6, 2020
• Est. primary completion date: April 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Skin Toxicity

Intervention

Drug:
• Doxycycline 50Mg Tablet
Doxycycline administered p.o once daily at a 50 mg dose for 6 weeks beginning on Day -1

Locations

Country	Name	City	State
Spain	Hospital Punta Europa	Algeciras
Spain	Hospital San Pedro de Alcántara	Cáceres
Spain	Hospital Puerta del Mar	Cadiz
Spain	Hospital Puerto Real	Cadiz
Spain	Hospital Clinico San Cecilio	Granada
Spain	Hospital Juan Ramón Jiménez	Huelva
Spain	Hospital de Jerez	Jerez De La Frontera
Spain	Hospital Virgen Macarena	Sevilla

Sponsors (3)

Lead Sponsor	Collaborator
Fundacion CRIS de Investigación para Vencer el Cáncer	Amgen, Apices Soluciones S.L.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Quality of life of patients during the treatment	Change in Dermatology Life Quality Index (DLQI) score	Up to 7 weeks
Secondary	Incidence of Treatment-Emergent Adverse Events	Number of adverse events per patient	Up to 6 weeks