eSCOUT: Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted Therapy

Sponsor

The Christie NHS Foundation Trust (Other)

Overall Status

Completed

CT.gov ID

NCT01225744

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Locations

Arm

Duration (Months)

15.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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

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

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: Cetuximab Drug: Irinotecan Drug: Oxaliplatin Drug: UFT	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

47 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study Evaluating the Use of Concurrent Cetuximab, Irinotecan, Oxaliplatin and UFT in the First Line Treatment of Patients With Metastatic Colorectal Cancer

Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

May 1, 2013

Actual Study Completion Date :

May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cetuximab plus Irinotecan, Oxaliplatin and UFT Cetuximab plus Irinotecan, Oxaliplatin, UFToral	Drug: 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 . Other Names: Erbitux 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. Other Names: Camptosar 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. Other Names: Eloxatin 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. Other Names: Tegafur Uracil

Arm

Intervention/Treatment

Experimental: Cetuximab plus Irinotecan, Oxaliplatin and UFT

Cetuximab plus Irinotecan, Oxaliplatin, UFToral

Drug: 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 .

Other Names:

Erbitux

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.

Other Names:

Camptosar

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.

Other Names:

Eloxatin

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.

Other Names:

Tegafur

Uracil

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	North Wales Cancer Treatment Centre	Llansantffraid Glan Conwy	United Kingdom	LL18 5UJ
2	The Royal Marsden	London and Surrey	United Kingdom
3	The Christie NHS Foundation Trust	Manchester	United Kingdom	M20 4BX