Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency (MESH)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by Royal Marsden NHS Foundation Trust.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00952016
First received: July 31, 2009
Last updated: December 3, 2013
Last verified: August 2009
  Purpose

To assess the efficacy of methotrexate in a genetically selected population of patients with advanced colorectal cancer, who have loss of a particular gene, MSH2. The efficacy of methotrexate will be evaluated by the proportion of cases that have a significant response to treatment (objective response rate).


Condition Intervention Phase
Advanced Colorectal Cancer
Drug: Methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Non-randomised Phase II Trial of Methotrexate in Metastatic Colorectal Cancer With MSH2 Deficiency

Resource links provided by NLM:


Further study details as provided by Royal Marsden NHS Foundation Trust:

Primary Outcome Measures:
  • Objective response rate, to include complete response and partial response, as defined radiologically using RECIST (Response, Evaluation Criteria in Solid Tumours) on imaging CT scans performed during treatment.

Secondary Outcome Measures:
  • Disease stabilisation rate; progression free survival; 1 year survival and median overall survival; Quality of Life assessment; toxicity assessment.

Estimated Enrollment: 29
Study Start Date: February 2009
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Methotrexate
    study subjects will receive methotrexate intravenously on day 1 and day 8 of a 3 weekly cycle.
Detailed Description:

The study will involve treating 29 subjects with methotrexate given intravenously. All subjects will receive treatment; there is no control arm or randomisation. The subjects will be known to have deficiency of MSH2, or a mutation (genetic change) in MSH2 that stops it functioning normally. This can either be demonstrated by testing for loss of MSH2 protein in the tumour itself, or by the demonstration of a mutation in the MSH2 gene in the subject's blood.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of metastatic or locally recurrent colorectal carcinoma
  • Aged 18 years or older
  • Paraffin embedded histological material available for analysis
  • Either confirmed loss of expression of MSH2 on immunohistochemistry IHC or confirmed mutation in MSH2 on gene sequencing
  • Life expectancy of > 3 months

Exclusion Criteria:

  • Previous treatment with methotrexate, either for malignant or non-malignant disease, except when methotrexate was given at low dose with other drugs to modify their effects
  • Concomitant uncontrolled medical conditions
  • Concomitant metastatic malignancy apart from non-melanotic skin cancers and carcinoma in situ of the uterine cervix in the last 10 years
  • Any contraindication to treatment with methotrexate (as this will affect safety)
  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: NCT00952016

Contacts
Contact: Prof David Cunningham +44 02086613156 david.cunningham@rmh.nhs.uk
Contact: Dr Madeleine Hewish +44 02071535332 madeleine.hewish@icr.ac.uk

Locations
United Kingdom
The Royal Marsden NHS Foundation Trust Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Contact: Dr Madeleine Hewish    +44 02071535340    madeleine.hewish@icr.ac.uk   
Principal Investigator: Prof David Cunningham         
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
  More Information

No publications provided

Responsible Party: The Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00952016     History of Changes
Other Study ID Numbers: CCR3107
Study First Received: July 31, 2009
Last Updated: December 3, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee

Keywords provided by Royal Marsden NHS Foundation Trust:
colorectal cancer
MSH2
metastatic

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014