KIT/PDGFR wild type GastroIntestinal Stromal Tumor (GIST) MedDRA version: 20.0 Level: HLGT Classification code 10017991 Term: Gastrointestinal neoplasms malignant and unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Stivarga
Product Name: regorafenib
Product Code: [regorafenib]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: REGORAFENIB
Current Sponsor code: REGORAFENIB
Other descriptive
Sponsors
GRUPO ESPAñOL DE INVESTIGACIóN EN SARCOMAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female subjects =18 years of age - Histologically confirmed GIST KIT/PDGFR wild-type, unresectable or metastatic GIST (confirmed by central laboratory). Paraffin-embedded tumor block must be provided by all subjects during screening period. - Screening of mutations done in exon 11, 9, 13 and 17 in KIT gene and in 12 and 18 exons of PDGFR gene - Subjects must have at least one measurable lesion according to RECIST v1.1 criteria. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion prior to study enrolment. - Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Total Bilirubin = 1.5 x the upper normal limit (UNL). Documented Gilbert Syndrome is allowed if total bilirubin is mildly elevated (=6mg/dl). Alanine Aminotransferase (ALT) and aspartate aminotransferase (AST) = 3.0 x UNL (=5xUNL for subjects with liver involvement of GIST) Lipase =1.5 x UNL Serum Creatinine = 1.5 x UNL Glomerular filtration rate (GFR) = 30ml/mn/1.73 m2 according to the Modified Diet in Renal Disease (MDRD) abbreviated formula. International Normalized Ratio (INR) =1.5xUNL and partial thromboplastin time (PTT) or activated partial thromboplastine time (aPTT) =1.5xUNL. Subjects who are being treated with an anti-coagulant, such as warfarin or heparin, will be allowed to participate provided that no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standards of care. Platelet count =100000mm3, hemoglobin (Hb) = 9.0 g/dl, absolute neutrophil count (ANC) =1500/mm3. Blood transfusions to meet the inclusion criteria will not be allowed. Alkaline phosphatase limit = 2.5 x UNL (= 5x UNL for subjects with disease involving the liver) - Women of childbearing potential and men must agree to use adequate contraception from the moment of signing the Informed Consent Form until at least 3 months after the last study drug administration. The investigator or a designated associate is requested to advise the subject on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care. - Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1. Prior systemic treatment for GIST. However, patients that have relapsed after receiving imatinib during adjuvant setting are eligible . 2. Cancer other than GIST within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, and superficial bladder tumors (Ta (Non Invasive tumor), and Tis (Carcinoma In situ)). 3. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before the start of study medication. 4. Congestive Heart Failure New York Heart Association (NYHA) = class 2. 5. Unstable angina (angina symptoms at rest, new-onset angina, ie, within the lasts 3 months prior to entering study) or myocardial infarction (MI) within the past 6 months before the start of study medication. 6. Cardiac arrhythmias requiring anti-arrhytmic therapy (beta blockers or digoxin are permitted). 7. Uncontrolled hypertension (Systolic blood pressure > 140 mmHg or diastolic pressure > 90mmHg despite optimal medical management). 8. Subjects with pheochromocytoma. 9. Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months from start of study treatment. 10. Venous thrombotic events such as deep vein thrombosis within the 3 months before the start of study treatment. 11. Ongoing infection > grade 2 National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 12. Known history of human immunodeficiency virus (HIV) infection. 13. Subjects with seizure disorder requiring medication 14. Symptomatic metastasis in brain or meningeal tumors. 15. History of organ allograft. 16. Subjects with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event = NCI-CTCAE version 4.03 grade 3 or higher within 4 weeks prior to start of study treatment. 17. Non-healing wound, ulcer, or bone fracture. 18. Renal failure requiring hemo- or peritoneal dialysis. 19. Dehydration NCI-CTCAE version 4.03 grade = 1 20. Substance abuse or medical, psychological, or social conditions that may interfere with the subject´s participation in the study or evaluation of the study results. 21. Known hypersensitivity to the study drug, study drug class, or excipients in the formulation. 22. Any illness or medical conditions that are unstable or could jeopardize the safety of the subject and his/her compliance in the study 23. Interstitial lung disease with ongoing signs and symptoms at the time of screening. 24. Subjects unable to swallow oral medication 25. Persistent proteinuria of NCI-CTCAE version 4.03 grade 3 or higher (>3.5g/24hrs), measured by urine protein creatinine ratio on a random urine sample) 26. Any malabsorption condition. 27. Left Ventricular Ejection Fraction (LVEF) < 50% or below the LLN for the institution (whichever is higher). 28. Pleural effusion or ascites that causes respiratory compromise (= NCI-CTCAE version 4.03 grade 2 dyspnea)
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time that patients remains free of disease progression; Disease evalutaion by CHOI measured in terms of tumor size and density; Evaluation of metabolic response by PET; Safety evaluation;Timepoint(s) of evaluation of this end point: Tumor imaging assessment will be performed every 8 weeks; Every 8 weeks from start of regorafenib treatment; After 1 month of treatment; Every 28 days, up to 30 days from last regorafenib administration | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Disease Control Rate (DCR);Secondary Objective: Progression Free Survival (PFS) Overall Survival (OS) Responses determined by CHOI Correlation with Translational Research Safety (Adverse events CTCAE v4.03) Early metabolic response by PET scan Quality of Life: EQ-ED-5L and QLQ-C30;Primary end point(s): Disease Control Rate (DCR);Timepoint(s) of evaluation of this end point: Imaging assessment will be performed every 8 cycles during study. | — |
Countries
France, Italy, Spain
Contacts
Public ContactClinical Trial Unit
Italian Sarcoma Group
Outcome results
None listed