Clinical trial NCT01225744: Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted Therapy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: The Christie NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2010-10-21
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Objective response rate (according to RECIST criteria)
timeFrame: 8 weeks post starting treatment
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 8 week intervals post starting treatment
measure: Overall survival (OS; all causes of death).
timeFrame: 3 years post treatment
measure: Toxicity
timeFrame: 2 months post starting treatment
measure: Resectability of liver, lung and pelvic disease after chemotherapy
timeFrame: 8 weekly intervals from the start of treatment
measure: Time to progression (TTP)
timeFrame: 8 weekly intervals following starting treatment
Other outcomes:
Locations:
city: Llansantffraid Glan Conwy
country: United Kingdom
facility: North Wales Cancer Treatment Centre
city: London and Surrey
country: United Kingdom
facility: The Royal Marsden
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Christie NHS Foundation Trust
name: Mark Saunders
role: PRINCIPAL_INVESTIGATOR
References: