Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted Therapy (eSCOUT)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Suzanne Rowland, Christie Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01225744
First received: October 20, 2010
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Cetuximab
Drug: Irinotecan
Drug: Oxaliplatin
Drug: UFT
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Christie Hospital NHS Foundation Trust:

Primary Outcome Measures:
  • Objective response rate (according to RECIST criteria) [ Time Frame: 8 weeks post starting treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 week intervals post starting treatment ] [ Designated as safety issue: No ]
    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). [ Time Frame: 3 years post treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 months post starting treatment ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: 8 weekly intervals from the start of treatment ] [ Designated as safety issue: No ]
  • Time to progression (TTP) [ Time Frame: 8 weekly intervals following starting treatment ] [ Designated as safety issue: No ]
    This is defined as the time from start of treatment to the time of documented radiological progression of disease locally


Enrollment: 47
Study Start Date: April 2009
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225744

Locations
United Kingdom
North Wales Cancer Treatment Centre
Llansantffraid Glan Conwy, United Kingdom, LL18 5UJ
The Royal Marsden
London and Surrey, United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Christie Hospital NHS Foundation Trust
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Mark Saunders Christie NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Suzanne Rowland, Clinical Trials Project Manager, Christie Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01225744     History of Changes
Other Study ID Numbers: 07_DOG03_133
Study First Received: October 20, 2010
Last Updated: June 10, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Irinotecan
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 15, 2014