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)

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

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:

1. Development of acneiforme follicular exanthema >= grade 2
2. Duration until development of acneiforme follicular exanthema >= grade 2
3. Development of paronychia
4. Development skin fissure (hand and foot)
5. Objective remission according RECIST 1.1
6. Rate of secondary resections of liver metastasis with a curative approach
7. Assessment of safety and tolerability
8. Overall survival
9. Progression free survival

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: FOLFIRI + Cetuximab

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

• Study Type: Interventional
• Enrollment (Anticipated): 165
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany, 55131
    • Universitätsmedizin Mainz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: FOLFIRI + Cetuximab

Drug: FOLFIRI + Cetuximab; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival rate at 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival		up to end of follow-up-phase (36 months)
ORR	Objective response rate over the entire treatment period	approximately 12 months
OS	Overall survival time	The time from regsitration date to the date of death
Duration until development of acneiforme follicular exanthema >= grade 2	Duration until development of acneiforme follicular exanthema >= grade 2 during treatment-phase	approximately 12 months
Development of paronychia	Development of paronychia during treatment-phase	approximately 12 months
Development of skin fissure (hand and foot)	Development of skin fissure (hand and foot) during treatment-phase	approximately 12 months
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	approximately 12 months
Assessment of safety and tolerability	Assessment of safety and tolerability during treatment phase	approximately 12 months
Development of acneiforme follicular exanthema >= grade2	Development of acneiforme follicular exanthema >= grade2 during treatment phase	approximately 12 months

Collaborators and Investigators

• Sponsor: Dr. Carl Schimanski
• Investigators: Principal Investigator: Carl Christoph Schimanski, PD Dr. med., Universitätsmedizin Mainz

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Anticipated): March 1, 2015
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: March 11, 2011
• First Submitted That Met QC Criteria: March 15, 2011
• First Posted (Estimate): March 16, 2011

Study Record Updates

• Last Update Posted (Estimate): December 18, 2013
• Last Update Submitted That Met QC Criteria: December 17, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: first-line treatment; rash; vitamin K1; Phase IV Study; Metastatic Colorectal Cancer (mCRC; Cetuximab (Erbitux); acneiform follicular exanthema
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Exanthema; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: DERMATUX