Patients with Advanced Gastrointestinal Stromal Tumors MedDRA version: 21.1 Level: PT Classification code 10051066 Term: Gastrointestinal stromal tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: QINLOCK® (ripretinib)
Product Name: QINLOCK® (ripretinib)
Pharmaceutical Form: Tablet
INN or Proposed INN: DCC-2618
CAS Number: 1442472-39-0
Current Sponsor code: DCC-2618
Concentration un
Sponsors
Deciphera Pharmaceuticals, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients = 18 years of age at the time of informed consent. 2. Histologic diagnosis of GIST and must be able to provide an archival tumor tissue sample, otherwise, a fresh biopsy is required. 3. Molecular pathology report with mutational status of KIT/PDGFRA must be available. Mutation status must be identified using a tissue based PCR/sequencing assay. Molecular pathology report with mutation status of KIT/PDGFRA must be provided to the Sponsor for review prior to randomization. If the molecular pathology report is not available or insufficient, an archival tumor tissue sample or fresh biopsy is required for mutation status confirmation by the central laboratory prior to randomization. 4. Patients must have progressed on imatinib or have documented intolerance to imatinib. Imatinib treatment must have been discontinued 10 days prior to the first dose of study drug. All prior imatinib treatment will count as one line of therapy (e.g. adjuvantimatinib and dose escalation of imatinib). 5. Eastern Cooperative Oncology Group (ECOG) PS of = 2 at screening. 6. Female patients of childbearing potential must have a negative serum beta-human chorionic gonadotrophin (ß-hCG) pregnancy test at screening and 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 contraception requirements outlined in the Protocol. 8. Patients must have at least 1 measurable lesion according to mRECIST Version 1.1 (non-nodal lesions must be = 1.0 cm in the long axis or = double the slice thickness in the long axis) within 21 days prior to the first dose of study drug. 9. Adequate organ function and bone marrow reserve as indicated by the following central laboratory assessments performed at screening: a. Absolute Neutrophil Count (ANC) = 1000/µL b. Hemoglobin = 8 g/dL c. Platelet count = 75,000/µL d. Total bilirubin = 1.5 x the upper limit of normal (ULN) e. Aspartate transaminase (AST) and alanine transaminase (ALT) = 3 x ULN (= 5x ULN in the presence of hepatic metastases) f. Creatinine clearance = 50 ml/min based on Cockcroft Gault estimation g. Prothrombin time (PT), international normalized ratio (INR) and partial thromboplastin time (PTT) = 1.5 x ULN. Patients on a stable regimen of anticoagulant therapy for at least one month prior to the first dose of study drug 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. 10. Resolution of all toxicities from prior therapy to = Grade 1 (or patient baseline) within 1 week prior to the first dose of study drug (excluding alopecia and = Grade 3 clinically asymptomatic lipase, amylase, and creatine phosphokinase (CPK) laboratory abnormalities). 11. The patient is capable of understanding and complying with the protocol and the patient has signed the informed consent document. Signed informed consent form (ICF) must be obtained before any study-specific procedures are performed and the patient must agree to not participate in any other interventional clinical trial while on treatment in this clinical trial. Participation in a noninterventional study (including observational studies) is permitted. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 286 F.1.3 Elderly (>=65 years) yes F.1.3.1 Nu
Exclusion criteria
Exclusion criteria: 1. Treatment with any other line of therapy in addition to imatinib for advanced GIST. Imatinib-containing combination therapy in the first-line setting is not allowed. 2. Patients with a prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical trial are not eligible. For example, patients receiving adjuvant cancer treatment are not eligible if those medications are potentially active against GIST or excluded per protocol. NOTE: Patients with a history of breast cancer, requiring continued hormonal treatment (e.g. anti-estrogen or an aromatase inhibitor) may continue treatment. Patients with a history of prostate cancer, requiring continued support with luteinizing hormone-releasing hormone (LHRH)agonists, with or without androgens, may continue treatment. NOTE: Patients may not be part of an ongoing or have prior participation in an investigational drug study within 30 days of screening. 3. Patient has known active central nervous system metastases. 4. New York Heart Association class II-IV heart disease, myocardial infarction within 6 months of cycle 1 day 1, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure. 5. Left ventricular ejection fraction (LVEF) 450 ms in males or > 470 ms in females at screening or history of long QT syndrome. 9. Use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A4, including certain herbal medications (e.g. St. John's Wort) within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of study drug, and consumption of grapefruit or grapefruit juice within 14 days prior to the first dose of study drug. Please refer to the Indiana University Department of Medicine website (http://medicine.iupui.edu/clinpharm/ddis/maintable/) for guidance on medications that inhibit/induce CYP3A4 enzymes. See Section 5.12.3.3 in the Protocol. 10. Use of known substrates or inhibitors of 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 for inhibitors and substrates (https://www.fda.gov/Drugs/DevelopmentApprovalProcess/Developme ntResources/DrugInteractionsLabeling/ucm093664.htm). See Section 5.12.3.2. 11. Major surgeries (e.g. abdominal laparotomy) within 4 weeks of the first dose of study drug. All major surgical wounds must be healed and free of infection or dehiscence before the first dose of study drug. 12. 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. 13. Known human immunodeficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy (progression-free survival [PFS]) of DCC-2618 by independent radiologic review in patients with advanced gastrointestinal stromal tumors (GIST) who have previously received first-line therapy with imatinib;Secondary Objective: • To assess objective response rate (ORR) by independent radiologic review using modified RECIST (mRECIST) criteria • To assess Overall Survival (OS);Primary end point(s): Efficacy PFS based on independent radiologic review using modified RECIST (mRECIST) (Appendix 17.1). mRECIST criteria includes: • No lymph nodes chosen as target lesions; enlarged lymph nodes followed as non-target lesions; • No bone lesions chosen as target lesions; • PET 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 (e.g. 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.;Timepoint(s) of evaluation of this end point: The primary endpoint of PFS (reported in weeks) is defined as the interval between the date of randomization and the earliest documented evidence of disease progression based on the independent radiologic review, or death due to any cause. Patients who undergo surgical resection of target or non-target lesions, who have received other anticancer treatments, or patients who do not have a documented date of progression or death due to any cause will be censored at the date of the last assessment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy • ORR (confirmed CR + confirmed PR) based on independent radiologic review using mRECIST criteria • OS The primary and secondary endpoints will be analyzed for both the KIT Exon 11 (Exon 11 ITT) and the All Patients (AP ITT) population. Safety Safety endpoints that will be evaluated include treatment-emergent adverse events (TEAEs), AESIs, SAEs, dose reduction or discontinuation of study drug due to toxicity; and changes from baseline in ECOG PS, vital signs, ECGs, LVEF, dermatologic examinations, and clinical laboratory parameters. Pharmacokinetics • Correlation of PK exposure with efficacy/safety • Population-based PK parameters ;Timepoint(s) of evaluation of this end point: Objective response rate: to be assigned a status of a CR or PR, changes in tumor measurements must be confirmed by repeat assessments that must be performed at least 4 weeks after the criteria for response are first met. Patients with unknown or missing response will be treated as non responders, that is, they will be included in the denominator when calculating the proportion. Time to confirmed response (CR or PR) (reported in weeks) is defined as the interval between the date of first dose of study medication and the earliest date of first documented confirmed CR or confirmed PR. Patients who do not have a confirmed PR or CR will be censored at the date of the last adequate assessment. | — |
Countries
Argentina, Australia, Belgium, Canada, Chile, Czechia, Czech Republic, France, Germany, Hungary, Israel, Italy, Korea, Democratic People's Republic of, Netherlands, Norway, Poland, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactSophie Higgins
Deciphera Pharmaceuticals, LLC
Outcome results
None listed