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

NCT00975897 | Completed Phase 2

• 5 other identifiers: CDR0000648235UKM-MRC-FOCUS3-CR12EUDRACT-2008-008323-15ISRCTN83171665EU-20960
• Study Type: interventional
• Target: 3,240
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (11)

• 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

Interventions

bevacizumab BIOLOGICAL

cetuximab BIOLOGICAL

fluorouracil DRUG

irinotecan hydrochloride DRUG

leucovorin calcium DRUG

oxaliplatin DRUG

RNA analysis GENETIC

cytogenetic analysis GENETIC

fluorescence in situ hybridization GENETIC

gene expression analysis GENETIC

mutation analysis GENETIC

protein expression analysis GENETIC

diagnostic laboratory biomarker analysis OTHER

immunohistochemistry staining method OTHER

questionnaire administration OTHER

cognitive assessment PROCEDURE

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Medical Research Council: lead

Study Sites (3)

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Belfast City Hospital Trust Incorporating Belvoir Park Hospital

Belfast, Northern Ireland, BT8 8JR, United Kingdom

Location

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, CF14 2TL, United Kingdom

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Cetuximab; Fluorouracil; Irinotecan; Leucovorin; Oxaliplatin; Cytogenetic Analysis; In Situ Hybridization, Fluorescence; Gene Expression Profiling; Immunohistochemistry; Mental Status and Dementia Tests

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; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Histological Techniques; Nucleic Acid Hybridization; Histocytochemistry; Immunologic Techniques; Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Timothy Maughan, MD

  Velindre NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: September 11, 2009
• First Posted: September 14, 2009
• Study Start: July 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: December 1, 2012
• Last Updated: December 19, 2013

Record last verified: 2011-08

Locations

GB (3)