Patient case: 70-year-old male with non-small cell lung cancer; genetic feature: KRAS (G12C)

Clinical trial: Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted Therapy

Summary: A Phase II trial to demonstrate the response rate, using the Response evaluation criteria in solid tumours (RECIST) criteria, of patients with locally advanced / metastatic colorectal cancer treated with combination of irinotecan, oxaliplatin, UFT and cetuximab.
  ENDPOINTS Primary: Objective response rate (RECIST) Secondary: Progression free survival (PFS), Overall survival (OS) Toxicity (CTCAE), Resectability of liver, lung and pelvic disease after chemotherapy, Time to progression (TTP).
  POPULATION: The trial aims to recruit 50 patients with inoperable, metastatic colorectal cancer ELIGIBILITY: Histologically confirmed colorectal adenocarcinoma Normal haematology and adequate renal and liver function Written informed consent and able to attend follow-up for at least 3 months TREATMENT 4 weekly cycles of chemotherapy with alternating irinotecan (day 1) and oxaliplatin(day 15). Cetuximab every 2 weeks and oral UFT with Leucovorin for 3 weeks every 4 weeks.
  DURATION First patient recruited April 2009. Accrual to take place over 24 months Follow-up will continue until death or for a minimum of 3 years


Eligibility: Inclusion Criteria:
  -  Histologically confirmed adenocarcinoma of the colon or rectum.
  -  Patients must not have a mutation of K-ras
  -  Inoperable metastatic or locoregional disease (synchronous or recurrence)
  -  No previous chemotherapy for established metastatic disease (adjuvant chemotherapy must have been completed more than 6 months prior to trial entry)
  -  Measurable or evaluable disease
  -  Bone marrow function: neutrophil count >1.5 x109/l and platelet count >150 x109/l
  -  Hepatobiliary function: serum bilirubin <1.5 x upper limit of normal (ULN); ALP <5 x ULN; transaminase (AST or ALT) <3 x ULN.(≤ 5 if liver mets are present)
  -  Renal function: estimated creatinine clearance >50 ml/min, or measured Glomerular filtration rate (GFR) (EDTA or creatinine clearance) in normal range
  -  ECOG performance status 0-1 and considered fit and able to undergo all possible treatments
  -  For women of child-bearing potential a negative pregnancy test is required and adequate contraceptive precautions such as a sheath for their partner must be used
  -  For men - adequate contraception such as a sheath must be used
  -  Patients must give written, informed consent
  -  Life expectancy ≥ 3 months.
  Exclusion Criteria:
  -  Patients that have a K-ras mutation
  -  Concurrent uncontrolled medical illness, or other previous or current malignant disease likely to interfere with protocol treatments or comparisons
  -  Partial or complete bowel obstruction
  -  Prior EGFR antibody therapy
  -  Age <18
  -  Chronic diarrhoea or inflammatory bowel disease
  -  Known Pyruvate Dehydrogenase Phosphatase (DPD) deficiency
  -  Gilbert's syndrome or other congenital abnormality of biliary transport
  -  Previous transplant surgery, requiring immunosuppressive therapy
  -  Regular / uncontrolled angina or cardiac arrhythmias
  -  Clinically relevant coronary artery disease. History of Myocardial infarction in the last 12 months
  -  Previous investigational agent in the last 4 weeks
  -  Metastatic disease to brain
  -  Any pregnant or lactating women
  -  Patients receiving therapy with haloginated antiviral drugs (eg: sorivudine)
  -  Patients who have experienced life-threatening toxicities with fluoropyrimidines treatment
  -  Patients suffering from any condition that may affect the absorption of UFT or folinic acid.
  -  Patients with known deficiency of or are on inhibitors of cytochrome P450 2A6
  -  Patients who have previously had radiotherapy to the abdomen or pelvis in the last 6 months
  -  Any medical or psychological condition that in the opinion of the investigator would not enable the patient to complete the study or knowingly give informed consent

Relevance to patient case: not relevant