Dual Targeting of EGFR With Cetuximab and Afatinib to Treat Refractory wtKRAS Metastatic Colorectal Cancer
A Multicentric Randomized Phase II Trial Evaluating Dual Targeting of EGFR Using the Combination of Cetuximab and Afatinib Versus Cetuximab Alone in Patients With Chemotherapy Refractory wtKRAS Metastatic Colorectal Cancer
  • Phase

    Phase 2
  • Study Type

  • Status

    Completed No Results Posted
  • Study Participants

This is a multicentric, phase II and open label study.75 patients are expected to be randomized in 35 centers. The main objective is to assess the efficacy and safety of Afatinib -cetuximab combo versus cetuximab alone in treatment of patients with refractory wtKRAS metastatic colorectal cancer.
Patients who will sign the inform consent will be enrolled into one of two groups. Group A will receive Afatinib ( 40mg per day) and Cetuximab (500mg/m2)every two weeks until progression. Group B will receive Cetuximab (500mg/m2) alone every two weeks until progression and after progression,patients from group B will receive afatinib (group A treatment) until progression. The criteria for evaluation will be tumor response and progression documented by CT scan and according to RECIST criteria version 1.1.

Patient will also sign a inform consent before participating in biological study. The aim of this translational study is to collect tumor and blood sample in order to determine, the biological factors which are predictive of the response to treatment.
Study Started
Oct 31
Primary Completion
Nov 30
Study Completion
Dec 31
Last Update
May 08

Drug Cetuximab + Afatinib

Afatinib taken orally, cetuximab administered intravenously

  • Other names: Erbitux

Drug Cetuximab

Cetuximab administered intravenously

  • Other names: Erbitux

Arm A: Cetuximab + Afatinib Experimental

Afatinib 40 mg daily Cetuximab 500 mg/m2 every 2 weeks until progression

Arm B : Cetuximab alone Active Comparator

Cetuximab 500mg/m2 every 2 weeks until progression After progression: Cetuximab 500mg/m2 + Afatinib 40 mg per day until progression


Inclusion Criteria:

Metastatic colorectal cancer expressing the wtKRAS status
No previous EGFR targeted therapy.
Must have failed a prior regimen containing irinotecan for metastatic disease and a prior regimen containing oxaliplatin for metastatic disease
Must have previously received a thymidylate synthase inhibitor (eg, fluorouracil, capecitabine, raltitrexed, or fluorouracil-uracil) at any point for treatment of colorectal cancer (CRC)
Life expectancy of at least 3 months.
Patient with ECOG ≤ 1
Patients aged ≥ 18.
Patient with measurable lesions according to RECIST criteria (version 1.1) with spiral CT scan and defined as ≥ 10 mm in longest diameter and 2X the slice thickness for extra nodal lesions and/or > 15 mm in short axis diameter for nodal lesions
Patient able to receive adequate oral nutrition of ≥ 1500 calories per day and free of significant nausea and vomiting

Patient with adequate organ function:

Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
Haemoglobin ≥ 9 g/dL
Platelets (PTL) ≥ 100 x 109/L
AST/ALT ≤ 3 x ULN (≤ 5 x ULN in case of liver metastases)
GammaGT < 3 x ULN (< 5 x ULN in case of liver involvement)
Bilirubin ≤ 1.5 x ULN
Creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula)
Adequate contraception if applicable.
Ability to take oral medication in the opinion of the investigator
Patient able and willing to comply with study procedures as per protocol
Patient able to understand and willing to sign and date the written voluntary informed consent form at screening visit prior to any protocol-specific procedures
Patient affiliated to a social security regimen

Exclusion Criteria:

Previous EGFR targeted therapy.
Mutant KRAS status
Prior severe reaction to a monoclonal antibody
No heart failure or coronary heart disease symptoms Clinically relevant cardiovascular abnormalities, as judged by the investigator, such as, but not limited to, uncontrolled hypertension, congestive heart failure NYHA classification > III, unstable angina, myocardial infarction within six months prior to randomisation, or poorly controlled arrhythmia
Cardiac left ventricular dysfunction with resting ejection fraction of less than institutional lower limit of normal (if no lower limit of normal is defined in the institution, the lower limit is 50%)
Symptomatic brain metastases requiring treatment
Major surgery within 28 days or minor surgery within 14 days of the start of the study treatment
Radiotherapy less than two weeks prior to the start of the study treatment
Systemic chemotherapy, hormonal therapy, immunotherapy ≤ 21 days before study treatment
No major comorbidity that may preclude the delivery of treatment or active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes.
Concomitant occurrence of another cancer, or history of cancer within the past five years except in situ carcinoma of the cervix treated or basal cell carcinoma or squamous cell carcinoma.
Known pre-existing interstitial lung disease
Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn's disease, malabsorption, or CTCAE grade >2 diarrhea of any etiology
Pregnant woman or lactating woman.
Persons deprived of liberty or under guardianship.
Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Previous history of keratitis, ulcerative keratitis or severe dry eye.
No Results Posted