Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With Anti-EGFR and Chemotherapy (DERMIA) (DERMIA)
Primary Purpose
Skin Toxicity
Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Doxycycline 50Mg Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Skin Toxicity
Eligibility Criteria
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.
Sites / Locations
- Hospital Punta Europa
- Hospital Puerta del Mar
- Hospital Puerto Real
- Hospital San Pedro de Alcántara
- Hospital Clinico San Cecilio
- Hospital Juan Ramón Jiménez
- Hospital de Jerez
- Hospital Virgen Macarena
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Doxycycline
Arm Description
Doxycycline 50 mg p.o. daily during 6 weeks
Outcomes
Primary Outcome Measures
Efficacy in the prevention of skin toxicity
Monitoring of skin toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events
Secondary Outcome Measures
Quality of life of patients during the treatment
Change in Dermatology Life Quality Index (DLQI) score
Incidence of Treatment-Emergent Adverse Events
Number of adverse events per patient
Full Information
NCT ID
NCT03448731
First Posted
February 19, 2018
Last Updated
April 7, 2020
Sponsor
Fundacion CRIS de Investigación para Vencer el Cáncer
Collaborators
Amgen, Apices Soluciones S.L.
1. Study Identification
Unique Protocol Identification Number
NCT03448731
Brief Title
Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With Anti-EGFR and Chemotherapy (DERMIA)
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
May 10, 2018 (Actual)
Primary Completion Date
April 6, 2020 (Actual)
Study Completion Date
April 6, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundacion CRIS de Investigación para Vencer el Cáncer
Collaborators
Amgen, Apices Soluciones S.L.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Skin Toxicity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Doxycycline
Arm Type
Experimental
Arm Description
Doxycycline 50 mg p.o. daily during 6 weeks
Intervention Type
Drug
Intervention Name(s)
Doxycycline 50Mg Tablet
Intervention Description
Doxycycline administered p.o once daily at a 50 mg dose for 6 weeks beginning on Day -1
Primary Outcome Measure Information:
Title
Efficacy in the prevention of skin toxicity
Description
Monitoring of skin toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events
Time Frame
During 6-week skin treatment
Secondary Outcome Measure Information:
Title
Quality of life of patients during the treatment
Description
Change in Dermatology Life Quality Index (DLQI) score
Time Frame
Up to 7 weeks
Title
Incidence of Treatment-Emergent Adverse Events
Description
Number of adverse events per patient
Time Frame
Up to 6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patricia Ramirez-Daffós, MD
Organizational Affiliation
Hospital Universitario Puerta del Mar
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Punta Europa
City
Algeciras
Country
Spain
Facility Name
Hospital Puerta del Mar
City
Cadiz
Country
Spain
Facility Name
Hospital Puerto Real
City
Cadiz
Country
Spain
Facility Name
Hospital San Pedro de Alcántara
City
Cáceres
Country
Spain
Facility Name
Hospital Clinico San Cecilio
City
Granada
Country
Spain
Facility Name
Hospital Juan Ramón Jiménez
City
Huelva
Country
Spain
Facility Name
Hospital de Jerez
City
Jerez De La Frontera
Country
Spain
Facility Name
Hospital Virgen Macarena
City
Sevilla
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35776185
Citation
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.
Results Reference
derived
Learn more about this trial
Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With Anti-EGFR and Chemotherapy (DERMIA)
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