LY3200882 and Capecitabine in Advanced Resistant TGF-beta Activated Colorectal Cancer (EORTC1615)

Exclusion Criteria

• •1. Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment;
• •2. Known or suspected dihydropirimidine dehydrogenase deficit (Mutant for DPD\*2A genotype, 1236 GA genotype, 1679TG genotype and 2846A\>T genotype);
• •3. Symptomatic or untreated leptomeningeal disease;
• •4. Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enrol. Brain metastasis must be stable with verification by imaging (e.g. brain MRI or CT (\<21 days before start of treatment) completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs or corticosteroids;
• •5. History of cardiac disease, including myocardial infarction within 6 months before study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension, major cardiac abnormalities, a predisposition for developing aneurysms including family history of aneurysms, Marfan syndrome, bicuspid aortic valve, or evidence of damage to the large vessels of the heart.
• •6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LY3200882 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection);
• •7. Woman who are pregnant or breast feeding;
• •8. Radio- or chemotherapy within the last 2 weeks prior to receiving the first dose of investigational treatment. Palliative radiation (1x 8Gy) is allowed;
• •9. Patients who have undergone any major surgery within the last 2 weeks prior to starting study drug or who would not have fully recovered from previous surgery;
• •10. Active infection requiring systemic antibiotics or uncontrolled infectious disease;
• •11. Patients with a known history of hepatitis B or C or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients;
• •12. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study;
• •13. Known hypersensitivity to one of the study drugs or excipients.
• •14. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \<1% per year (when used consistently and correctly) during the treatment period and for at least 90 days after the last dose of LY3200882 and/or capecitabine. More information is available in section 5.2.4.
• •15. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined in section 5.2.4.