gastrointestinal sromal tumors
Conditions
Interventions
This is a 2-arm, randomized, placebo-controlled, double-blind, international,
multicenter
study comparing the efficacy of DCC-2618 to placebo in patients who have
received
treatment with prior antic
Sponsors
Deciphera Pharmaceuticals, LLC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patients >=18 years of age at the time of informed consent 2. Histologic diagnosis of GIST 3.Patients must have progressed on imatinib, sunitinib, and regorafenib or have documented intolerance to any of these treatments despite dose modifications. 4. ECOG PS of 0 to 2 at screening. 5. Able to provide an archival tumor tissue sample if no anticancer therapy was administered since the sample was collected; otherwise, a fresh tumor tissue sample is required prior to the first dose of study drug. 6. Female patients of childbearing potential must have a negative serum beta-human chorionic gonadotrophin (β-hCG) pregnancy test at screening and a negative pregnancy test at Cycle 1 Day 1 prior to the first dose of study drug. 7. Patients of reproductive potential must agree to follow the contraception requirements outlined in Section 6.11.10 of the study protocol. 8. The patient is capable of understanding and complying with the protocol and has signed the informed consent document. A signed informed consent form must be obtained before any study-specific procedures are performed. 9. At least 1 measurable lesion according to modified RECIST Version 1.1 (non-nodal lesions must be >=1.0 cm in the long axis or >=double the slide thickness in the long axis) within 21 days prior to the first dose of study drug. 10. Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments performed at screening. • Absolute neutrophil count >=1000/µL • Hemoglobin >=8 g/dL • Platelet count >=75,000/µL • Total bilirubin =50 mL/min based on either urine collection or Cockcroft Gault estimation. • Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time 1.5 x ULN if, in the opinion of the Investigator, the patient is suitable for the study. An adequate rationale must be provided to the Sponsor prior to randomization. 11. Resolution of all toxicities from prior therapy to
Exclusion criteria
Exclusion criteria: 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 (refer to Section 5.12.3 of the 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) 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 infect
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: PFS based on independent radiologic review using modified RECIST ( ; Appendix 17.1). Modified RECIST criteria includes: • No lymph nodes chosen as target lesions; enlarged lymph nodes followed as non target lesions; • No bone lesions chosen as target lesions; • Positron emission tomography not acceptable for radiological evaluation; • A progressively growing new tumor nodule within a pre-existing tumor mass must meet the following criteria to be considered as unequivocal evidence of progression according to the modification of RECIST Version 1.1: (a) the lesion is at least 2 cm in size and definitively a new active GIST lesion (eg, enhancing with contrast or other criteria to rule out artefact); or (b) the lesion has to be expanding on at least 2 sequential imaging studies. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary Efficacy Endpoint: • Objective response rate (confirmed CR + confirmed PR) Secondary Efficacy Endpoints: • TTP based on independent radiologic review • OS • Time to best response • PFS based on Investigator assessment • Quality of life as determined by changes from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 30 item and EuroQol 5-Dimension 5-Level • Disease control rate (complete response [CR] + partial response [PR] + stable disease) at 12 weeks | — |
Countries
Netherlands
Outcome results
None listed