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

NCT03448731 | Completed Phase 2

• 2 other identifiers: DERMIA2017-004413-98
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Skin Toxicity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Quality of life of patients during the treatment

  Up to 7 weeks

• Incidence of Treatment-Emergent Adverse Events

  Up to 6 weeks

Study Arms (1)

Doxycycline

EXPERIMENTAL

Doxycycline 50 mg p.o. daily during 6 weeks

Drug: Doxycycline 50Mg Tablet

Interventions

Doxycycline 50Mg Tablet DRUG

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

Doxycycline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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)
• 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

Sponsors & Collaborators

• Fundacion CRIS de Investigación para Vencer el Cáncer: lead
• Amgen: collaborator
• Apices Soluciones S.L.: collaborator

Study Sites (8)

Hospital Punta Europa

Algeciras, Spain

Location

Hospital Puerta del Mar

Cadiz, Spain

Location

Hospital Puerto Real

Cadiz, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, Spain

Location

Hospital Clinico San Cecilio

Granada, Spain

Location

Hospital Juan Ramón Jiménez

Huelva, Spain

Location

Hospital de Jerez

Jerez de la Frontera, Spain

Location

Hospital Virgen Macarena

Seville, Spain

Location

Related Publications (1)

• 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.

  PMID: 35776185 DERIVED

MeSH Terms

Interventions

Doxycycline; Tablets

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Patricia Ramirez-Daffós, MD

  Hospital Universitario Puerta del Mar

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2018
• First Posted: February 28, 2018
• Study Start: May 10, 2018
• Primary Completion: April 6, 2020
• Study Completion: April 6, 2020
• Last Updated: April 8, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8)