{"registry": "ISRCTN", "registryId": "ISRCTN90061546", "source": "https://www.isrctn.com/ISRCTN90061546", "apiSource": "https://www.isrctn.com/api/trial/ISRCTN90061546/format/default", "fetchedAt": "2026-10-07T17:00:58.468750Z", "license": "CC BY 4.0", "licenseSource": "https://www.isrctn.com/page/faqs#licence-to-post", "study": {"title": "FOCUS4: Molecular selection of therapy in colorectal cancer", "scientificTitle": "Molecular selection of therapy in colorectal cancer: a molecularly stratified randomised controlled trial programme", "acronym": "FOCUS4", "hypothesis": "FOCUS4 is an umbrella, or platform, for testing novel agents in biomarker-defined subpopulations of first-line advanced disease colorectal cancer patients who are not considered candidates for potentially curative surgery. It is also a trial of a new strategy for testing stratified approaches to therapy in any biologically complex tumour type. See Trial Schema in the Trial Protocol. \nThe backbone of the platform is 16 weeks of treatment with any standard first line colorectal cancer treatment, after which, as is frequently standard practice in the UK and Europe, there is a programmed treatment break for responding and stable patients. During that break, either new agent(s) or placebo is administered. The primary outcome measure for assessing the activity of the new treatment is progression free survival in the interval (time to death or progression requiring resumption of chemotherapy). \nAt present, four coherent biomarker-stratified groups can be identified and trials will be established in each of these cohorts as follows: \n- BRAF mutant \n- PIK3CA mutation or complete loss of PTEN on IHC \n- KRAS or NRAS mutant \n- All wild type (no mutations of BRAF, PIK3CA, KRAS or NRAS) \n- Unclassified biomarker results \nFor each of these subgroups, a relevant novel agent or combination is to be tested in an adaptive double blind randomised trial design with multiple interim analyses for early termination if there is no strong evidence of worthwhile activity (the principles are derived from the Multi-Arm, Multi-Stage (MAMS) design). \n\nFOCUS4 will open with one molecularly stratified trial (FOCUS4-D) testing AZD8931 (a HER 1,2 3 inhibitor) against placebo in patients stratified into the All wild-type cohort. In addition, a non-stratified trial (FOCUS4-N) will be open for patients whose biomarker results are unclassified or who are unable or unwilling to participate in the molecular trial available to them. The molecularly stratified trials for the BRAF, PIK3CA, KRAS/NRAS mutant cohorts are still in development and will be updated on this site when they open. Target recruitment levels will also be adjusted at that time.", "primaryOutcome": "Progression free survival, determined by multi-stage design of each molecular trial", "secondaryOutcome": "Overall survival: becomes a joint primary outcome if the trial continues to the final stage analysis", "intervention": "\n\tAZD8931 (for FOCUS4-D), HER 1,2 3 Inhibitor; Capecitabine (FOCUS4-N), Oral 5FU pro drug\nRandomisation is performed using minimisation with a random element. Minimisation factors are based upon known prognostic factors for outcome.\n\nFor FOCUS4-D: The trial medication is orally administered twice daily over a continuous 28 day cycle.  Patients are followed up every 4 weeks for symptoms and toxicity when they also collect their double-blind placebo controlled prescription from hospital pharmacy. CT scans are performed every 8 weeks to determine progression status of the tumour. \n\nFor FOCUS4-N: Capecitabine is an oral administration taken twice daily for 14 days followed by a 7 day break before recommencing the 21 day cycle. All patients from both arms are required to attend an outpatients appointment every 3-4 weeks to assess symptoms and toxicity and for those in the capecitabine arm, they need to collect their next prescription. All patients have a CT scan every 8 weeks to determine progression status of the tumour.\n\tDrug\n\tPhase II\n\tCapecitabine, sapitinib (AZD8931), adavosertib (AZD1775)\n      ", "condition": "\n\tTopic: National Cancer Research Network; Subtopic: Colorectal Cancer; Disease: Colon, Rectum\n\tCancer\n\t\n      ", "studyDesign": "Randomised; Interventional; Design type: Treatment", "overallEndDate": "2020-10-30T00:00:00.000Z", "clinicalTrialsGovNumber": "", "lastUpdated": "2023-04-26T15:24:34.570374Z", "eligibility": {"inclusion": "Registration inclusion criteria (please refer to the protocol for eligibility for randomisation) \n1. Male/female patients at least 18 years old\n2. Formalin fixed paraffin embedded (FFPE) tumour block taken prior to the commencement of standard chemotherapy and available for biomarker analysis\n3. Histologically confirmed adenocarcinoma of the colon/rectum\n4. Inoperable metastatic or locoregional disease (synchronous or metachronous)\n5. WHO performance status 0, 1 or 2\n6. Unidimensionally measurable disease RECIST 1.1 classification\n7. Have had an electronically accessible CT scan performed within 4 weeks prior to start of standard chemotherapy\n8. Platelet count < 400 x 109/L prior to start of standard chemotherapy\n9. For women of childbearing potential, a negative pregnancy test and acceptable contraceptive precautions\n10. Effective contraception for male patients if the risk of conception exists\n11. Consent for screening of an archival FFPE tumour block for biomarker analysis (PIS1 & CF1)\n13. Patients should have sufficient capacity for informed consent and provided signed informed consent", "exclusion": "Registration exclusion criteria (please refer to the protocol for eligibility for randomisation) \n1. Previous systemic palliative chemotherapy using a different regimen for established advanced or metastatic disease\n2. Adjuvant chemotherapy given in the last 6 months\n3. Patients with brain metastases\n4. Pregnant and lactating women", "ageRange": "Adult", "gender": "All", "participantType": "Patient"}, "recruitment": {"recruitmentStart": "2013-12-01T00:00:00.000Z", "recruitmentEnd": "2017-11-30T00:00:00.000Z", "recruitmentStatusOverride": "", "recruitmentStartStatusOverride": "", "targetEnrolment": "384", "totalFinalEnrolment": ""}, "countries": ["United Kingdom", "England"], "locations": [{"name": "MRC CTU", "city": "London", "state": "", "country": "United Kingdom", "zip": "WC2B 6NH"}], "sponsors": [{"organisation": "The Medical Research Council (MRC) (UK)", "sponsorType": "Research council", "rorId": "https://ror.org/03x94j517"}], "funders": [{"name": "Cancer Research UK (UK)", "fundRef": "http://dx.doi.org/10.13039/501100000289"}, {"name": "Efficacy and Mechanism Evaluation Programme; Grant Codes: 11/100/50", "fundRef": "http://dx.doi.org/10.13039/501100001922"}]}, "studySha256": "ddab53447beaca94599080112f1bd2ec82f73883dba740cd6f767f4919d8659f"}