FOCUS 3 - the feasibility of molecular selection of therapy using KRAS, BRAF and topo-1 in patients with metastatic or locally advanced colorectal cancer

Not Applicable

Completed

• Conditions: Metastatic or locally advanced colorectal cancer; Cancer; Malignant neoplasm of rectosigmoid junction

• Registration Number: ISRCTN83171665
• Lead Sponsor: Medical Research Council (UK)

Brief Summary

2014 Results article in http://www.ncbi.nlm.nih.gov/pubmed/24743706 results

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-07-24
• Study Completion: 2011-03-31
• Last Update Posted: 7 November 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

Amendments as of 09/02/2010:
Please note that as of the above date, point 4 below was updated as follows:
4. Unidimensionally measurable disease (Response Evaluation Criteria in Solid Tumours [RECIST] criteria). Baseline computed tomography (CT) scan must be performed within 5 weeks prior to treatment.

Initial inclusion criteria at time of registration:
1. Male/female patients aged at least 18 years or over
2. Confirmed colorectal adenocarcinoma:
2.1. Either previous or current histologically confirmed primary adenocarcinoma of colon or rectum, together with clinical or radiological evidence of locally advanced disease or metastatic disease or both
2.2. Or histologically confirmed metastatic adenocarcinoma, together with clinical and/or radiological evidence of colorectal primary tumour
3. Inoperable metastatic or locoregional disease
4. Unidimensionally measurable disease (Response Evaluation Criteria in Solid Tumours [RECIST] criteria). Baseline computed tomography (CT) scan must be performed within 4 weeks prior to treatment.
5. Adjuvant chemotherapy with 5-fluorouracil (5FU) +/- folinic acid (FA), capecitabine or oxaliplatin combinations may have been given, if chemotherapy completed at least 6 months prior to trial entry. QUASAR 2 patients who have continued bevacizumab for 6 months following completion of chemotherapy are eligible immediately following completion of bevacizumab (Avastin).
6. Rectal chemoradiotherapy with 5FU +/- FA or capecitabine may have been given, if completed at least 1 month prior to trial entry
7. Fit to receive any of the treatment regimens proposed as defined by:
7.1. World Health Organization (WHO) performance status (PS) 0, 1 or 2 and considered by responsible consultant to be fit to undergo combination chemotherapy
7.2. Baseline laboratory tests (within 1 week prior to randomisation normally):
7.2.1. Neutrophils greater than or equal to 1.5 x 10^9/l and platelet count greater than or equal to 100 x 10^9/l
7.2.2. Alkaline phosphatase less than or equal to 5 x upper limit of normal (ULN), serum bilirubin less than or equal to 1.25 x ULN and serum transaminase (either aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) less than or equal to 2.5 x ULN
7.2.3. Estimated creatinine clearance (Cockcroft and Gault) greater than or equal to 30 ml/min or measured glomerular filtration rate (GFR) (ethylenediaminetetraacetic acid [EDTA] clearance) greater than or equal to 30 ml/min
8. For women of childbearing potential, negative pregnancy test and adequate contraceptive precautions
9. Effective contraception for male patients if the risk of conception exists
10. Written informed consent including consent to the immediate release of tumour blocks for analysis of molecular markers

Exclusion Criteria

1. Patients expected to be suitable for surgical resection of metastatic disease after response to chemotherapy as decided by the multidisciplinary team (MDT)
2. Previous systemic chemotherapy for metastatic disease
3. Pregnant or lactating women
4. Inability to attend or comply with treatment or follow-up scheduling
5. Patients who are unfit for the chemotherapy regimens in this protocol, e.g.:
5.1. Severe uncontrolled concurrent medical illness (including poorly controlled angina, uncontrolled hypertension or very recent myocardial infarction (MI) (i.e. in previous 3 months), likely to interfere with protocol treatments
5.2. History of severe peptic ulcer diseases
5.3. Any psychiatric or neurological condition which is felt likely to compromise the patient's ability to give informed consent or to comply with oral medication
5.4. Nephrotic syndrome
5.5. Known coagulopathy
5.6. Patients requiring ongoing therapy with ciclosporin-A (due to interaction with irinotecan)
6. Patients requiring ongoing treatment with a contraindicated concomitant medication
7. Patients with another previous or current malignant disease which, in the judgement of the treating investigator, is likely to interfere with FOCUS 3 treatment or assessment of response
8. Patients with known hypersensitivity reactions to any of the components of the study treatments
9. Patients with brain metastases
10. Patients with a personal or family history suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency or with known DPD deficiency
11. History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent
12. History of surgery less than 4 weeks prior to commencement of cycle 1

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. Of those patients randomised, in how many patients was the interval between registration and the provision of results to the investigator to allow randomisation less than or equal to 10 working days<br> 2. Of those patients randomised, in how many patients was the interval between registration and the date of randomisation less than or equal to 10 working days<br>