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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00975897
First received: September 11, 2009
Last updated: December 18, 2013
Last verified: August 2011
  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: 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 [ Designated as safety issue: No ]
  • Number of patients in which the interval between registration and randomization (RZ) is ≤ 10 days [ Designated as safety issue: No ]
  • Efficacy of fluorouracil with vs without irinotecan hydrochloride, fluorouracil, and leucovorin calcium (IrMdG) in low topo-1 tumors [ Designated as safety issue: No ]
  • Progression-free survival of patients with high topo-1 tumors treated with IrMdG with or without oxaliplatin [ Designated as safety issue: No ]
  • Efficacy of IrMdG with vs without cetuximab in K-ras wildtype tumors [ Designated as safety issue: No ]
  • Efficacy of IrMdG with vs without bevacizumab in K-ras mutant tumors [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time from release of tumor block to receipt by pathology lab [ Designated as safety issue: No ]
  • If applicable, reason that RZ did not occur [ Designated as safety issue: No ]
  • Time from registration to treatment start [ Designated as safety issue: No ]
  • Time from data presentation to investigator to date of RZ [ Designated as safety issue: No ]
  • Reproducibility of K-ras, BRAF, and topo-1 results [ Designated as safety issue: No ]
  • Distribution frequencies [ Designated as safety issue: No ]
  • Costs of molecular testing [ Designated as safety issue: No ]
  • Toxicity according to NCI CTCAE v.3 [ Designated as safety issue: Yes ]
  • Response rates [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Attitudes of patients about tests and treatment [ Designated as safety issue: No ]

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: 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

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00975897     History of Changes
Other Study ID Numbers: CDR0000648235, UKM-MRC-FOCUS3-CR12, EUDRACT-2008-008323-15, ISRCTN83171665, EU-20960
Study First Received: September 11, 2009
Last Updated: December 18, 2013
Health Authority: United States: Federal Government

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
Fluorouracil
Oxaliplatin
Irinotecan
Bevacizumab
Cetuximab
Camptothecin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on April 15, 2014