Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted Therapy
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT01225744
- Lead Sponsor
- The Christie NHS Foundation Trust
- Brief 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 47
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cetuximab plus Irinotecan, Oxaliplatin and UFT Oxaliplatin Cetuximab plus Irinotecan, Oxaliplatin, UFToral Cetuximab plus Irinotecan, Oxaliplatin and UFT Irinotecan Cetuximab plus Irinotecan, Oxaliplatin, UFToral Cetuximab plus Irinotecan, Oxaliplatin and UFT Cetuximab Cetuximab plus Irinotecan, Oxaliplatin, UFToral Cetuximab plus Irinotecan, Oxaliplatin and UFT UFT Cetuximab plus Irinotecan, Oxaliplatin, UFToral
- Primary Outcome Measures
Name Time Method Objective response rate (according to RECIST criteria) 8 weeks post starting treatment Patients will receive triphasic CT scans at 8 weekly intervals after treatment has started. Patients remain on trial until disease progression or at the discretion of the Investigator.
- Secondary Outcome Measures
Name Time Method Progression Free Survival 8 week intervals post starting treatment Progression will be defined according to RECIST criteria with appropriate clinical assessment and radiological investigations. This will be measured from the time of entry into the study.
Overall survival (OS; all causes of death). 3 years post treatment The date and cause of death will be recorded for each patient. Survival will be measured from the date of registration into the trial and will be reported on an intention-to treat-basis.
Toxicity 2 months post starting treatment Grade 3 or 4 Adverse Events experienced from the start of treatment up to the point of the first response CT scheduled for 8 weeks after treatment start date.
Number and description of Serious Adverse Events experienced will also be recorded.Resectability of liver, lung and pelvic disease after chemotherapy 8 weekly intervals from the start of treatment Time to progression (TTP) 8 weekly intervals following starting treatment This is defined as the time from start of treatment to the time of documented radiological progression of disease locally
Trial Locations
- Locations (3)
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
North Wales Cancer Treatment Centre
🇬🇧Llansantffraid Glan Conwy, United Kingdom
The Royal Marsden
🇬🇧London and Surrey, United Kingdom