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Study of Tumor Tissue Testing in Selecting Treatment for Patients With Metastatic or Locally Advanced Colorectal Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00975897
First Posted: September 14, 2009
Last Update Posted: December 19, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
National Cancer Institute (NCI)
  Purpose

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors select the best treatment for patients and predict their response to treatment.

PURPOSE: This randomized phase II/III trial is studying how well tumor tissue testing works in selecting treatment for patients with metastatic or locally advanced colorectal cancer.


Condition Intervention Phase
Colorectal Cancer Biological: bevacizumab Biological: cetuximab Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: oxaliplatin Genetic: RNA analysis Genetic: cytogenetic analysis Genetic: fluorescence in situ hybridization Genetic: gene expression analysis Genetic: mutation analysis Genetic: protein expression analysis Other: diagnostic laboratory biomarker analysis Other: immunohistochemistry staining method Other: questionnaire administration Procedure: cognitive assessment Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: FOCUS 3 - A Study to Determine the Feasibility of Molecular Selection of Therapy Using KRAS, BRAF and Topo-1 in Patients With Metastatic or Locally Advanced Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Topoisomerase-1 (topo-1) and K-ras, BRAF results obtained within 10 working days after registration
  • Number of patients in which the interval between registration and randomization (RZ) is ≤ 10 days
  • Efficacy of fluorouracil with vs without irinotecan hydrochloride, fluorouracil, and leucovorin calcium (IrMdG) in low topo-1 tumors
  • Progression-free survival of patients with high topo-1 tumors treated with IrMdG with or without oxaliplatin
  • Efficacy of IrMdG with vs without cetuximab in K-ras wildtype tumors
  • Efficacy of IrMdG with vs without bevacizumab in K-ras mutant tumors

Secondary Outcome Measures:
  • Time from release of tumor block to receipt by pathology lab
  • If applicable, reason that RZ did not occur
  • Time from registration to treatment start
  • Time from data presentation to investigator to date of RZ
  • Reproducibility of K-ras, BRAF, and topo-1 results
  • Distribution frequencies
  • Costs of molecular testing
  • Toxicity according to NCI CTCAE v.3
  • Response rates
  • Progression-free survival
  • Attitudes of patients about tests and treatment

Estimated Enrollment: 3240
Study Start Date: July 2009
Study Completion Date: December 2012
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal adenocarcinoma meeting 1 of the following criteria:

    • Prior or recurrent primary adenocarcinoma of the colon or rectum with clinical or radiological evidence of locally advanced or metastatic disease
    • Metastatic adenocarcinoma with clinical and/or radiological evidence of colorectal primary tumor
  • Inoperable metastatic or locoregional disease

    • Patients suitable for surgical resection of metastatic disease after response to first-line or adjuvant chemotherapy not allowed and should be considered for the New-EPOC trial study
  • Unidimensionally measurable disease (according to RECIST criteria)
  • Must have completed adjuvant chemotherapy with fluorouracil +/- leucovorin calcium (FU +/- LC), capecitabine, or oxaliplatin combinations in the past 6 months

    • QUASAR 2 patients who have continued bevacizumab for 6 months following completion of chemotherapy are allowed immediately after completion of bevacizumab
  • Rectal chemotherapy with FU +/- LC or capecitabine for allowed if completed ≥ 1 month ago
  • Single tumor block available
  • No brain metastasis

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Alkaline phosphatase ≤ 5 times upper limit of normal (ULN)
  • Serum bilirubin ≤ 1.25 times ULN
  • AST or ALT ≤ 2.5 times ULN
  • Creatinine clearance ≥ 30 mL/min OR GFR ≥ 30 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Considered fit to undergo combination chemotherapy, with none of the following conditions:

    • Severe uncontrolled concurrent medical illness likely to interfere with protocol treatments, including any of the following:

      • Poorly controlled angina
      • Uncontrolled hypertension
      • Myocardial infarction within the past 3 months
    • History of severe peptic ulcer disease
    • Any psychiatric or neurological condition that is likely to compromise the patient's ability to give informed consent or to comply with oral medication
    • Nephrotic syndrome
    • Known coagulopathy
  • No prior or current malignant disease that, in the judgement of the treating investigator, is likely to interfere with FOCUS 3 treatment or assessment of response
  • No known hypersensitivity reactions to any of the components of the study treatments
  • No personal or family history suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency or with known DPD deficiency
  • No history of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant precluding informed consent
  • Not able to attend or comply with treatment or follow-up scheduling

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 4 weeks since prior surgery
  • No prior systemic chemotherapy for metastatic disease
  • No ongoing therapy with cyclosporin-A
  • No ongoing treatment with a contraindicated concomitant medication
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00975897


Locations
United Kingdom
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
Belfast, Northern Ireland, United Kingdom, BT8 8JR
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, United Kingdom, CF14 2TL
Sponsors and Collaborators
Medical Research Council
Investigators
Principal Investigator: Timothy Maughan, MD Velindre NHS Trust
  More Information

Publications:
Maughan T, Wilson RH, Williams GT, et al.: Developing a biomarker-stratified trial design in advanced colorectal cancer: The MRC FOCUS 3 feasibility study. [Abstract] J Clin Oncol 29 (Suppl 15): A-TPS165, 2011.

ClinicalTrials.gov Identifier: NCT00975897     History of Changes
Other Study ID Numbers: CDR0000648235
UKM-MRC-FOCUS3-CR12
EUDRACT-2008-008323-15
ISRCTN83171665
EU-20960
First Submitted: September 11, 2009
First Posted: September 14, 2009
Last Update Posted: December 19, 2013
Last Verified: August 2011

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the colon
recurrent colon cancer
stage III colon cancer
stage IV colon cancer
adenocarcinoma of the rectum
recurrent rectal cancer
stage III rectal cancer
stage IV rectal cancer

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
Bevacizumab
Oxaliplatin
Irinotecan
Cetuximab
Fluorouracil
Levoleucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic