Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted Therapy

• Status: Completed
• Trial end date: 2013-05-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Christie NHS Foundation Trust
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Camptothecin; Cetuximab; Irinotecan; Oxaliplatin; Tegafur

Criteria

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