FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema (DERMATUX)
Primary Purpose
Colorectal Cancer Metastatic
Status
Unknown status
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
FOLFIRI + Cetuximab
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring Phase IV Study, Metastatic Colorectal Cancer (mCRC, Cetuximab (Erbitux), first-line treatment, acneiform follicular exanthema, rash, vitamin K1
Eligibility Criteria
Inclusion Criteria:
- Histologically-confirmed metastatic colorectal cancer (primary tumor or metastasis)
- Confirmation of KRAS wildtype status
- Confirmation of EGFR-Expression in the tumor
- Stadium IV
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Qualified for an application of FOLFIRI + Cetuximab treatment
- Signed patient informed consent form
- Of either gender and aged 18 years or more
- Estimated lifespan more than 3 months
- Measurable disease according to RECIST 1.1 guidelines. The evaluation has to be max. 4 weeks
- Effective and adequate contraceptive precautions of man or woman in a childbearing potential age (double barrier method)
- Leucocytes ≥ 3,0 x 10^9/L with neutrophils ≥ 1,5 x 10^9/L, thrombocytes ≥ 100 x 10^9/L, haemoglobin ≥ 5,6 mmol/L
- Serum bilirubin ≤ 1,5 x ULN (upper limit of normal)
- ALAT and ASAT ≤ 2,5 x ULN; if metastasis in liver, than ALAT and ASAT ≤ 5 x ULN
- Serum creatinin ≤ 1,5 x ULN
- If applicable a prior operation has to be min. 4 weeks ago, biopsy more than 1 week until initiation of treatment. Wounds of operations had to be completely cured
- No toxicity of prior treatments
Exclusion Criteria:
- KRAS-gene mutation
- Confirmation of non-EGFR-Expression
- Prior treatment with an EGRF-receptor inhibitor
- Prior chemotherapy of the mCRC, except (neo-)adjuvant therapy, which had to be ended min. 6 months before recruitment
- Experimental treatment medication within 30 days before recruitment
- Known hypersensitivity against components of the chemotherapy, cetuximab, doxycycline, Reconval K1 or Dermatop
- Rosacea
- Other chronic dermal diseases with development of papula or pustule
- Known lung fibrosis or interstitial pneumonitis or interstitial lung diseases
- keratitis, ulcerative keratitis or severe form of dry eye
- Pregnancy or breast feeding
- Brain metastasis
- Clinical relevant coronary heart disease, myocardial infarction within the last 12 months or high risk of uncontrollable arrhythmia
- Acute or subacute ileus or chronic colon-inflammation or chronic diarrhea
- Symptomatic peritoneal carcinomatosis
- Serious, non-healing wounds, ulcera or bone fractures
- Uncontrollable arterial hypertension
- Therapeutic anticoagulation (e.g. therapy with marcumar)
- Known dihydropyrimidine dehydrogenase deficiency
- Gilbert-Meulengracht-syndrome
- Other malignant tumours less than five years old. Exceptions include basocellular carcinoma or an in situ cancer of the cervix uteri if they are curative treated as well as an untreated, locally confined, asymptotic "low risk" (indolent) prostata carcinoma (Stage T ≤ T1-2a, PSA < 15 ng/ml, Gleason-Score ≤ 6 ).
- Known abuse of narcotic drugs or alcohol
- Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures
- Any significant concomitant disease that excludes the participation to the study
- Missing or limited juristic contractual capability
Sites / Locations
- Universitätsmedizin Mainz
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
FOLFIRI + Cetuximab
Arm Description
Outcomes
Primary Outcome Measures
Progression-free survival
Progression-free survival rate at 12 months
Secondary Outcome Measures
Progression-free survival
ORR
Objective response rate over the entire treatment period
OS
Overall survival time
Duration until development of acneiforme follicular exanthema >= grade 2
Duration until development of acneiforme follicular exanthema >= grade 2 during treatment-phase
Development of paronychia
Development of paronychia during treatment-phase
Development of skin fissure (hand and foot)
Development of skin fissure (hand and foot) during treatment-phase
Rate of secondary resections of metastasis of liver with a curative approach
Rate of secondary resections of metastasis of liver with a curative approach during treatment-phase
Assessment of safety and tolerability
Assessment of safety and tolerability during treatment phase
Development of acneiforme follicular exanthema >= grade2
Development of acneiforme follicular exanthema >= grade2 during treatment phase
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01315990
Brief Title
FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
Acronym
DERMATUX
Official Title
Non-randomized Phase-IV-study to Investigate the Efficacy of FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
Study Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Unknown status
Study Start Date
January 2011 (undefined)
Primary Completion Date
March 2015 (Anticipated)
Study Completion Date
March 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Carl Schimanski
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this interventional study is to assess the progression free survival (one year) of patients with treatment of FOLFIRI and cetuximab, combined with an optional dermal prophylaxis.
Further Objectives:
Development of acneiforme follicular exanthema >= grade 2
Duration until development of acneiforme follicular exanthema >= grade 2
Development of paronychia
Development skin fissure (hand and foot)
Objective remission according RECIST 1.1
Rate of secondary resections of liver metastasis with a curative approach
Assessment of safety and tolerability
Overall survival
Progression free survival
Detailed Description
Subjects with metastatic colorectal cancer and confirmed KRAS-wildtype status in 1st line therapy will be included in this phase IV-study. Subject will receive a regimen of FOLFIRI in combination with Cetuximab every two weeks during study treatment phase. Treatment continues until
disease progression
complete response
development of status of operability
an uncontrollable exanthema grade 3 or 4 or
intolerable toxicity is diagnosed. After study discontinuation or end of treatment, respectively, patients will be followed up until the the last patient was treated for 12 months and has completed the 36-months follow up phase. Tumor response will be evaluated (according to RECIST 1.1) every 12 weeks and at the end of study treatment
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Metastatic
Keywords
Phase IV Study, Metastatic Colorectal Cancer (mCRC, Cetuximab (Erbitux), first-line treatment, acneiform follicular exanthema, rash, vitamin K1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
165 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
FOLFIRI + Cetuximab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
FOLFIRI + Cetuximab
Intervention Description
Cetuximab (Erbitux® )- Cetuximab is a recombinant IgG1 chimeric monoclonal antibody directed against human epidermal growth factor receptor (EGFR).
FOLFIRI regimen
Administration Schedule:
Cetuximab at a initial dose 400 mg/sqm (first week), then 250 mg/sqm on day 1 and 8 Background Chemotherapy (every two weeks)
Irinotecan 180 mg/m² iv , 90 min on day 1
Folic acid (racemic) 400 mg/m², 120 min on day 1
5-FU 400 mg/m² bolus on day 1
5-FU 2400 mg/m² iv over 46 h on day 1 to 2
Primary Outcome Measure Information:
Title
Progression-free survival
Description
Progression-free survival rate at 12 months
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Progression-free survival
Time Frame
up to end of follow-up-phase (36 months)
Title
ORR
Description
Objective response rate over the entire treatment period
Time Frame
approximately 12 months
Title
OS
Description
Overall survival time
Time Frame
The time from regsitration date to the date of death
Title
Duration until development of acneiforme follicular exanthema >= grade 2
Description
Duration until development of acneiforme follicular exanthema >= grade 2 during treatment-phase
Time Frame
approximately 12 months
Title
Development of paronychia
Description
Development of paronychia during treatment-phase
Time Frame
approximately 12 months
Title
Development of skin fissure (hand and foot)
Description
Development of skin fissure (hand and foot) during treatment-phase
Time Frame
approximately 12 months
Title
Rate of secondary resections of metastasis of liver with a curative approach
Description
Rate of secondary resections of metastasis of liver with a curative approach during treatment-phase
Time Frame
approximately 12 months
Title
Assessment of safety and tolerability
Description
Assessment of safety and tolerability during treatment phase
Time Frame
approximately 12 months
Title
Development of acneiforme follicular exanthema >= grade2
Description
Development of acneiforme follicular exanthema >= grade2 during treatment phase
Time Frame
approximately 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically-confirmed metastatic colorectal cancer (primary tumor or metastasis)
Confirmation of KRAS wildtype status
Confirmation of EGFR-Expression in the tumor
Stadium IV
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Qualified for an application of FOLFIRI + Cetuximab treatment
Signed patient informed consent form
Of either gender and aged 18 years or more
Estimated lifespan more than 3 months
Measurable disease according to RECIST 1.1 guidelines. The evaluation has to be max. 4 weeks
Effective and adequate contraceptive precautions of man or woman in a childbearing potential age (double barrier method)
Leucocytes ≥ 3,0 x 10^9/L with neutrophils ≥ 1,5 x 10^9/L, thrombocytes ≥ 100 x 10^9/L, haemoglobin ≥ 5,6 mmol/L
Serum bilirubin ≤ 1,5 x ULN (upper limit of normal)
ALAT and ASAT ≤ 2,5 x ULN; if metastasis in liver, than ALAT and ASAT ≤ 5 x ULN
Serum creatinin ≤ 1,5 x ULN
If applicable a prior operation has to be min. 4 weeks ago, biopsy more than 1 week until initiation of treatment. Wounds of operations had to be completely cured
No toxicity of prior treatments
Exclusion Criteria:
KRAS-gene mutation
Confirmation of non-EGFR-Expression
Prior treatment with an EGRF-receptor inhibitor
Prior chemotherapy of the mCRC, except (neo-)adjuvant therapy, which had to be ended min. 6 months before recruitment
Experimental treatment medication within 30 days before recruitment
Known hypersensitivity against components of the chemotherapy, cetuximab, doxycycline, Reconval K1 or Dermatop
Rosacea
Other chronic dermal diseases with development of papula or pustule
Known lung fibrosis or interstitial pneumonitis or interstitial lung diseases
keratitis, ulcerative keratitis or severe form of dry eye
Pregnancy or breast feeding
Brain metastasis
Clinical relevant coronary heart disease, myocardial infarction within the last 12 months or high risk of uncontrollable arrhythmia
Acute or subacute ileus or chronic colon-inflammation or chronic diarrhea
Symptomatic peritoneal carcinomatosis
Serious, non-healing wounds, ulcera or bone fractures
Uncontrollable arterial hypertension
Therapeutic anticoagulation (e.g. therapy with marcumar)
Known dihydropyrimidine dehydrogenase deficiency
Gilbert-Meulengracht-syndrome
Other malignant tumours less than five years old. Exceptions include basocellular carcinoma or an in situ cancer of the cervix uteri if they are curative treated as well as an untreated, locally confined, asymptotic "low risk" (indolent) prostata carcinoma (Stage T ≤ T1-2a, PSA < 15 ng/ml, Gleason-Score ≤ 6 ).
Known abuse of narcotic drugs or alcohol
Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures
Any significant concomitant disease that excludes the participation to the study
Missing or limited juristic contractual capability
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carl Christoph Schimanski, PD Dr. med.
Organizational Affiliation
Universitätsmedizin Mainz
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitätsmedizin Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
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