FOCUS4: Molecular selection of therapy in colorectal cancer

INTERVENTION: AZD8931 (for FOCUS4‐D), HER 1,2 3 Inhibitor; Capecitabine (FOCUS4‐N), Oral 5FU pro drug Randomisation is performed using minimisation with a random element. Minimisation factors are based upon known prognostic factors for outcome. For 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. For 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. CONDITION: Topic: National Cancer Research Network; Subtopic: Colorectal Cancer; Disease: Colon, Rectum ; Cancer PRIMARY OUTCOME: Progression free survival, determined by multi‐stage design of each molecular trial SECONDARY OUTCOME: Overall survival: becomes a joint primary outcome if the trial continues to the final stage analysis INCLUSION CRITERIA: Registration inclusion criteria (please refer to the protocol for eligibility for randomisation) 1. Male/female patients at least 18 years old 2. Formalin fixed paraffin embedded (FFPE) tumour block taken prior to the commencement of standard chemotherapy and available for biomarker analysis 3. Histologically confirmed adenocarcinoma of the colon/rectum 4. Inoperable metastatic or locoregional disease (synchronous or metachronous) 5. WHO performance status 0, 1 or 2 6. Unidimensionally measurable disease RECIST 1.1 classification 7. Have had an electronically accessible CT scan performed within 4 weeks prior to start of standard chemotherapy 8. Platelet count < 400 x 109/L prior to start of standard chemotherapy 9. For women of childbearing potential, a negative pregnancy test and acceptable contraceptive precautions 10. Effective contraception for male patients if the risk of conception exists 11. Consent for screening of an archiv