Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted Therapy

NCT ID: NCT01225744

Last Updated: 2014-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2013-05-31

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

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab plus Irinotecan, Oxaliplatin and UFT

Cetuximab plus Irinotecan, Oxaliplatin, UFToral

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

Cetuximab will be prepared under Good Manufacturing practice (GMP) and supplied by Merck KGaA (Darmstadt, Germany) as a solution for intravenous infusion. It will be made up into 250ml with N/Saline.

Dose administered is 400mg/m2 and will be given on day 1 and day 15 of a 28 day cycle.Cetuximab will always be administered first, i.e. the cetuximab infusion should be completed one hour before any chemotherapy begins. The cetuximab dose must always be based on the body surface area(BSA). There is no restriction for cetuximab in patients with a BSA > 2 m2 .

Irinotecan

Intervention Type: DRUG

Dose is 180mg/m2 made up into 250ml with 5% dextrose or 0.9% saline. It will be administered as a short infusion over 60-90 minutes after a 60 minute gap left after cetuximab administration. Irinotecan is administered on day 1 of the 28 day cycle.

Oxaliplatin

Intervention Type: DRUG

Dose is 100mg/m2 and will be made up into 250ml with 5% dextrose. It will be administered as a short infusion over 120 minutes after the 60 minute gap left after cetuximab administration. Oxaliplatin is administered on day 15 of the 28 day cycle.

UFT

Intervention Type: DRUG

UFT dose is 250mg/m2 and is given in three divided doses with calcium folate 30mg p.o. tds on days 1-21 of the 28 day cycle. The highest dose of UFT should be given in the morning if the dose cannot be divided equally.

Interventions

Cetuximab

Cetuximab will be prepared under Good Manufacturing practice (GMP) and supplied by Merck KGaA (Darmstadt, Germany) as a solution for intravenous infusion. It will be made up into 250ml with N/Saline.

Dose administered is 400mg/m2 and will be given on day 1 and day 15 of a 28 day cycle.Cetuximab will always be administered first, i.e. the cetuximab infusion should be completed one hour before any chemotherapy begins. The cetuximab dose must always be based on the body surface area(BSA). There is no restriction for cetuximab in patients with a BSA > 2 m2 .

Intervention Type: DRUG

Irinotecan

Dose is 180mg/m2 made up into 250ml with 5% dextrose or 0.9% saline. It will be administered as a short infusion over 60-90 minutes after a 60 minute gap left after cetuximab administration. Irinotecan is administered on day 1 of the 28 day cycle.

Intervention Type: DRUG

Oxaliplatin

Dose is 100mg/m2 and will be made up into 250ml with 5% dextrose. It will be administered as a short infusion over 120 minutes after the 60 minute gap left after cetuximab administration. Oxaliplatin is administered on day 15 of the 28 day cycle.

Intervention Type: DRUG

UFT

UFT dose is 250mg/m2 and is given in three divided doses with calcium folate 30mg p.o. tds on days 1-21 of the 28 day cycle. The highest dose of UFT should be given in the morning if the dose cannot be divided equally.

Intervention Type: DRUG

Other Intervention Names

Erbitux; Camptosar; Eloxatin; Tegafur; Uracil

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

The Christie NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Suzanne Rowland

Clinical Trials Project Manager

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Saunders

Role: PRINCIPAL_INVESTIGATOR

Christie NHS Foundation Trust

Locations

North Wales Cancer Treatment Centre

Llansantffraid Glan Conwy, , United Kingdom

The Royal Marsden

London and Surrey, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

United Kingdom

Other Identifiers

07_DOG03_133

Identifier Type: -

Identifier Source: org_study_id