Metastatic soft tissue sarcoma MedDRA version: 15.1 Level: HLGT Classification code 10041299 Term: Soft tissue sarcomas System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: regorafenib
Pharmaceutical Form: Tablet
INN or Proposed INN: regorafenib
CAS Number: 755037-03-7
Current Sponsor code: regorafenib
Other descriptive name: REGORAFENIB
Concentration unit:
Sponsors
Centre Oscar Lambret
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years of age 2. Histological documentation of soft tissue (including uterus) sarcoma with available FFPE blocks obtained. After amendment 4: eligible soft tissue sarcomas are non-adipocytic soft tissue sarcomas. 3. Prior treatment with doxorubicin or other anthracyclin. Moreover, Patients eligible in the Cohort E must have received pazopanib 4. Metastatic disease not amenable to surgical resection with curative intent 5. Documentation of progression before study entry 6. Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST 1.1. 7. Eastern Cooperative Oncology Group (ECOG) performance status =1 Life expectancy of at least 3 months 8. Adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation: a. Absolute neutrophil count (ANC) =1,500/mm3 b. Platelets =100,000/mm3 c. Hemoglobin =9.0 g/dL d. Serum creatinine =1.5 x upper limit of normal (ULN) e. Glomerular filtration rate (GFR) =30 ml/min/1.73m2 f. AST and ALT =2.5 x ULN ( =5.0 × ULN for patients with liver involvement of their cancer g. Bilirubin =1.5 X ULN h. Alkaline phosphatase =2.5 x ULN (=5 x ULN with liver involvement of their cancer) i. Amylase and lipase =1.5 x ULN j. Spot urine must not show 1+ or more protein in urine or the patient will require a repeat urine analysis. If repeat urinanalysis shows 1+ protein or more, a 24-hour urine collection will be required and must show total protein excretion =65 years) yes F.1.3.1 Number of subjects for this age range 192
Exclusion criteria
Exclusion criteria: 1. More than 4 lines of systemic treatment for metastatic sarcoma 2. Histological subtypes listed in Appendix C (especially GIST, osseous sarcoma, embryonnal or alveolar rhabdomyosarcoma) Patients with liposarcoma are not eligible in the cohort E 3. Primary bone sarcoma 4. Prior treatment with regorafenib 5. Known history of or concomitant malignancy likely to affect life expectancy in the judgment of the investigator 6. Pregnant or breastfeeding patients. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment 7. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of Day 1 of treatment 8. Active cardiac disease including any of the following: Congestive heart failure (New York Heart Association [NYHA]) =Class 2, Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) 9. Uncontrolled hypertension. (Systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg despite optimal medical management) 10. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism 11. Ongoing infection >Grade 2 according to NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v. 4.0) 12. Known history of human immunodeficiency virus (HIV) infection 13. Known history of chronic hepatitis B or C 14. Patients with seizure disorder requiring medication 15. History of organ allograft 16. Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event > Grade 3 within 4 weeks of start of treatment 17. Non-healing wound, ulcer, or bone fracture 18. Renal failure requiring hemo- or peritoneal dialysis 19. Dehydration according to NCI-CTC v 4.0 Grade >1 20. Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results 21. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation 22. Interstitial lung disease with ongoing signs and symptoms at the time of informed consent 23. Inability to swallow oral medications, Any malabsorption condition 24. Pleural effusion or ascites that causes respiratory compromise (Grade 2 dyspnea)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the progression-free survival (PFS) ;Secondary Objective: - To evaluate progression-free rate at 3 and 6 months (PFR-3 and PFR-6), time to progression, response rate, duration of response and overall survival - To explore the growth modulation index in patients receiving regorafenib after randomization - To evaluate toxicity according to NCI-CTC AE V4.0. Exploratory - To identify potential predictive factors for regorafenib response.;Primary end point(s): Progression-free survival (PFS) according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and after central radiological review;Timepoint(s) of evaluation of this end point: Disease progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free rate at 3 and 6 months (PFR-3 and PFR-6), time to progression, response rate and duration of response, overall survival according to RECIST 1.1 criteria 2. Toxicity according to NCI-CTC AE V4.0 3. Growth modulation index 4. Potential predictive factors for regorafenib response …. Formalin fixed, paraffin embedded (FFPE) or fresh frozen tissue samples collected either from the primary tumor or from metastatic sites, or both will be analyzed. ;Timepoint(s) of evaluation of this end point: 1. 3 to 6 months 2. LVLS 3. Disease progression | — |
Countries
Austria
Contacts
Public ContactProject manager
Centre Oscar Lambret
Outcome results
None listed