Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favorable FcγRIIa (CD32) Genotype
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: Cetuximab
Intervention description: Cetuximab will be administered intravenously at a dose of 500 milligram per square meter (mg/m^2) every 2 weeks until disease progression, death, or consent withdrawal.
Intervention MeSH terms: Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 73.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: K-RAS; FcγRII/IIIa genotypes; CRC; Colorectal cancer

Summary:

      This national, multicenter, open-label phase 2 study without any control arm aims to evaluate
      the activity of cetuximab monotherapy in the treatment of refractory colorectal cancer in
      subjects with K-RAS mutated and FcγRIIa polymorphism tumors, in which there is no therapeutic
      alternative for treatment. Failure of the first and second line conventional therapeutic
      lines was documented.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent form signed by the subject

          -  Age greater than or equal to (>=) 18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
             (=<) 2

          -  Life expectancy of greater than (>) 2 months

          -  Histological confirmed colorectal cancer (CRC) with mutated K-RAS and favorable
             genotypes (any H in FcγRIIa-131). Selection will be done only based on Cluster of
             differentiation (CD)32 polymorphisms

          -  Epidermal growth factor receptor (EGFR) expression in his/her tumor sample

          -  Stage 4 metastatic disease, with at least 1 measurable lesion according to Response
             Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria, documented
             within 28 days prior to the study inclusion

          -  Tumor tissue sample available for the assessment of K-RAS status and FcγRIIa (CD32)
             genotype

          -  Subject who has received at least 2 prior therapeutic lines

          -  Adequate bone marrow function, defined as:

               -  haemoglobin > 9.0 gram per deciliter (g/dL)

               -  platelet count >100*10^9 per liter

               -  absolute neutrophil count (ANC) >=1.5*10^9/Liter

          -  Adequate hepatic and renal function, defined as:

               -  Serum bilirubin =<1.5 times the upper limit of normal (ULN)

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =<2.5*ULN in
                  absence of liver metastasis and ALT and AST =<5*ULN in the presence of liver
                  metastasis

               -  Alkaline phosphatase =<2.5*ULN or =<5 in the presence of liver metastasis or =<10
                  in the absence of liver metastasis

               -  Creatinine clearance >= 50 milliliter per minute (mL/min) (according to Cockcroft
                  and Gault formula) or serum creatinine <1.5*ULN

          -  Adequate recovery after recent surgery, chemotherapy or radiotherapy. Prior major
             surgery, chemotherapy, treatment with an investigational product or radiotherapy must
             have occurred at least 4 weeks before study inclusion

          -  Women of child-bearing potential must have a negative pregnancy test performed within
             7 days prior to the study inclusion. Postmenopausal women must be amenorrheic for at
             least 12 months. If the risk of conception exists both male and female subjects must
             use effective contraception (for example, abstinence, intrauterine device (IUD), oral
             contraceptive, double barrier method or to be surgically sterile) since the signature
             of the consent form until at least 6 months after the end of treatment or end of last
             dose, whichever occurs first

        Exclusion Criteria:

          -  Previous treatment with monoclonal antibodies against EGFR

          -  Toxicity, due to previous treatment, not resolved to Grade 1 before the subject's
             inclusion into the study

          -  Clinically relevant coronary disease or myocardial infarction, unstable angina, Grade
             >=2 congestive cardiac insufficiency according to New York Heart Association (NYHA)
             within 6 months before starting the study treatment

          -  Clinically significant vascular disease (for example, aortic aneurysm which requires
             surgery, pulmonary embolism, recent peripheral arterial thrombosis) within 12 months
             prior to starting the study treatment

          -  Evidence of uncontrolled brain metastases

          -  History of active neurological disease

          -  History of uncontrolled seizures

          -  History of lung fibrosis, acute pulmonary damage or interstitial pneumonia

          -  Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C
             infection, or presence of severe, uncontrolled intercurrent infections or other severe
             uncontrolled concomitant diseases

          -  Current Grade >=2 (National Cancer Institute Common Terminology Criteria for Adverse
             Events [NCI-CTCAE]) infection

          -  History of uncontrolled diabetes, uncontrolled hypertension or hepatic involvement

          -  Known or suspected allergy or hypersensitivity to cetuximab

          -  History of previous malignancy other than CRC occurring within 5 years before starting
             the study treatment, except for previously cured basal cell carcinoma of skin or
             carcinoma in situ of the cervix or urinary bladder treated more than 2 years before
             recruitment

          -  Participation in another treatment study with an investigational drug within the last
             30 days

          -  Pregnancy or lactation

          -  Any medical, psychological, psychiatric or social uncontrolled problem which may
             interfere in the participation of the subject in the study or in the evaluation of the
             study results

          -  Psychological, familiar or geographic conditions not allowing the adequate follow-up
             and adherence to the study protocol