This phase III trial is evaluating a new oral drug (DCC-2618) for the treatment of advanced gastrointestinal stromal tumours that have previously been treatedA Phase 3, INterVentional, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of DCC-2618 In Patients With AdvanCed Gastrointestinal Stromal TUmorS Who Have Received Treatment With Prior Anticancer Therapies

Exclusion

1. Treatment with anticancer therapy, including investigational therapy, or investigational procedures within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug. For prior biological therapies, eg, monoclonal antibodies with a half-life longer than 3 days, the interval must be at least 28 days prior to the first dose of study drug.
2. Prior treatment with DCC-2618
3. Prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of DCC-2618. Patients receiving adjuvant cancer treatment are not eligible if those medications are potentially active against GIST or excluded per protocol.
4. Patient has known active central nervous system metastases.
5. New York Heart Association class II - IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure.
6. Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks) or hemoptysis within 6 months before the first dose of study drug.
7. Venous thrombotic events (eg, deep vein thrombosis) or pulmonary arterial events (eg, pulmonary embolism) within 3 months before the first dose of study drug. Patients with venous thrombotic events ≥3 months before the first dose of study drug on stable anticoagulation therapy are eligible.
8. 12-lead electrocardiogram (ECG) demonstrating QT interval corrected by Fridericia's formula >450 ms in males or >470 ms in females at screening or history of long QT interval corrected syndrome.
9. Left ventricular ejection fraction (LVEF) <50% at screening.
10. Use of proton-pump inhibitors within 4 days prior to the first dose of study drug. Other medications that increase gastric pH, ie, histamine H2 receptor antagonists and antacids may be taken provided they are not administered within 2 hours before or after administration of study drug.
11. Use of strong or moderate inhibitors and inducers of cytochrome P450 (CYP) 3A4, including certain herbal medications (eg, St. John's Wort) and consumption of grapefruit or grapefruit juice within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug.
12. Use of known substrates or inhibitors of breast cancer resistance protein (BCRP) transporters within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug.
13. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug. Following major surgeries, >4 weeks prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence.
14. Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with interpretation of the study results, or predispose the patient to safety risks.
15. Known human immunodeficiency virus or hepatitis C infection only if the patient is taking medications that are excluded per protocol, active hepatitis B, or active hepatitis C infection.
16. If female, the patient is pregnant or lactating.
17. Known allergy or hypersensitivity to any component of the investigational drug product. Patients with a history of Stevens-Johnson syndrome on a prior TKI are excluded.

18. Gastrointestinal abnormalities including but not limited to:

    • inability to take oral medication
    • malabsorption syndromes
    • requirement for intravenous alimentation
19. Any active bleeding excluding hemorrhoidal or gum bleeding.