A 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
- Conditions
- gastrointestinal sromal tumors10017966
- Registration Number
- NL-OMON50251
- Lead Sponsor
- Deciphera Pharmaceuticals, LLC
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
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 <=1.5 x the upper limit of normal (ULN)
• Aspartate transaminase and alanine transaminase <=3 x ULN (<=5x ULN in the
presence of hepatic metastases)
• Serum creatinine <=1.5 x ULN or creatinine clearance >=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. Patients on a stable, maintenance regimen of
anticoagulant therapy for at least 30 days prior
to study drug administration may have PT/INR measurements >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 <=Grade 1 (or baseline)
within 1 week prior to the first dose of study drug (excluding alopecia and
<=Grade 3 clinically asymptomatic lipase, amylase, and creatine phosphokinase
laboratory abnormalities).
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) <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. Please refer to
the Indiana University Department of Medicine website
(http://medicine.iupui.edu/clinpharm/ddis/main-table/) for guidance on
medications that inhibit CYP3A4 enzymes.
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. Please refer to the US Food and Drug
Administration*s (FDA) website
(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/
DrugInteractionsLabeling/ucm093664.htm) for inhibitors and substrates.
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 infect
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>PFS based on independent radiologic review using modified RECIST ( ; Appendix<br /><br>17.1). Modified RECIST criteria includes:<br /><br>• No lymph nodes chosen as target lesions; enlarged lymph nodes followed as non<br /><br>target lesions;<br /><br>• No bone lesions chosen as target lesions;<br /><br>• Positron emission tomography not acceptable for radiological evaluation;<br /><br>• A progressively growing new tumor nodule within a pre-existing tumor mass<br /><br>must meet the following criteria to be considered as unequivocal evidence of<br /><br>progression according to the modification of RECIST Version 1.1: (a) the lesion<br /><br>is at least 2 cm in size and definitively a new active GIST lesion (eg,<br /><br>enhancing with contrast or other criteria to rule out artefact); or (b) the<br /><br>lesion has to be expanding on at least 2 sequential imaging studies.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Key Secondary Efficacy Endpoint:<br /><br>• Objective response rate (confirmed CR + confirmed PR)<br /><br><br /><br>Secondary Efficacy Endpoints:<br /><br>• TTP based on independent radiologic review<br /><br>• OS<br /><br>• Time to best response<br /><br>• PFS based on Investigator assessment<br /><br>• Quality of life as determined by changes from baseline in European<br /><br>Organisation for Research and Treatment of Cancer Quality of Life Questionnaire<br /><br>for Cancer 30 item and EuroQol 5-Dimension 5-Level<br /><br>• Disease control rate (complete response [CR] + partial response [PR] + stable<br /><br>disease) at 12 weeks</p><br>