Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted Therapy

NCT01225744 | Completed Phase 2 DMC

• 1 other identifier: 07_DOG03_133
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 3

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

Outcome Measures

Primary Outcomes (1)

• Objective response rate (according to RECIST criteria)

  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.

  8 weeks post starting treatment

Secondary Outcomes (5)

• Progression Free Survival

  8 week intervals post starting treatment

• Overall survival (OS; all causes of death).

  3 years post treatment

• Toxicity

  2 months post starting treatment

• 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

Study Arms (1)

Cetuximab plus Irinotecan, Oxaliplatin and UFT

EXPERIMENTAL

Cetuximab plus Irinotecan, Oxaliplatin, UFToral

Drug: Cetuximab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: UFT

Interventions

Cetuximab 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 .

Also known as: Erbitux

Cetuximab plus Irinotecan, Oxaliplatin and UFT

Irinotecan 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.

Also known as: Camptosar

Cetuximab plus Irinotecan, Oxaliplatin and UFT

Oxaliplatin 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.

Also known as: Eloxatin

Cetuximab plus Irinotecan, Oxaliplatin and UFT

UFT 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.

Also known as: Tegafur, Uracil

Cetuximab plus Irinotecan, Oxaliplatin and UFT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

North Wales Cancer Treatment Centre

Llansantffraid Glan Conwy, LL18 5UJ, United Kingdom

Location

The Royal Marsden

London and Surrey, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Irinotecan; Oxaliplatin; Tegafur; Uracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Fluorouracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Mark Saunders

  Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Trials Project Manager

Study Record Dates

• First Submitted: October 20, 2010
• First Posted: October 21, 2010
• Study Start: April 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 11, 2014

Record last verified: 2014-06

Locations

GB (3)