Patient case: 61-year-old male with Ampullary carcinoma. Genetic variant: KRAS. Other conditions: None.

Clinical trial: FOLFOXIRI Plus Panitumumab In Kras and Braf Wild-Type Metastatic Colorectal Cancer

Summary: The GONO-FOLFOXIRI regimen demonstrated higher activity and efficacy compared to FOLFIRI in a phase III trial. Panitumumab with oxaliplatin- or irinotecan-based doublets is feasible and associated with improved activity in KRAS codon 12-13 wild-type patients. BRAF and other RAS rare mutations have been suggested as additional potential biomarkers for anti-EGFR agents in metastatic colo-rectal cancer. The present study aims to demonstrate the feasibility and the activity of the first-line combination of the GONO-FOLFOXIRI regimen and Panitumumab in molecularly selected metastatic colo-rectal cancer patients.


Eligibility: Inclusion Criteria:
  -  Histologically confirmed colorectal adenocarcinoma;
  -  Availability of formalin-fixed paraffin embedded tumor block from primary or metastasis;
  -  KRAS and BRAF wild-type status of primary colorectal cancer or related metastasis;
  -  Unresectable and measurable metastatic disease according to RECIST criteria;
  -  Male or female, aged >/= 18 years and </= 75 years;
  -  ECOG PS < 2 if aged < 71 years;
  -  ECOG PS = 0 if aged 71-75 years;
  -  Life expectancy of more than 3 months;
  -  Adequate haematological function: ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9 g/dL;
  -  Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and transaminases ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN);
  -  Serum creatinine ≤ 1.5 x ULN;
  -  Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
  -  At least 6 weeks from prior radiotherapy and 4 weeks from surgery;
  -  Written informed consent to experimental treatment and pharmacogenomic analyses;
  -  Magnesium ≥ lower limit of normal;
  -  Calcium ≥ lower limit of normal.
  Exclusion Criteria:
  -  Prior palliative chemotherapy;
  -  Prior treatment with EGFR inhibitors;
  -  Symptomatic peripheral neuropathy ≥ 2 grade NCIC-CTG criteria;
  -  Presence or history of CNS metastasis;
  -  Active uncontrolled infections; active disseminated intravascular coagulation;
  -  Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix;
  -  Clinically significant cardiovascular disease, for example cerebrovascular accidents (CVA) (≤ 6 months before treatment start), myocardial infarction (≤ 6 months before treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF), uncontrolled arrhythmia;
  -  Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception;
  -  Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment;
  -  History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.

Relevance to patient case: not relevant