Metastatic soft tissue sarcoma MedDRA version: 20.0 Level: PT Classification code 10075333 Term: Soft tissue sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: stivarga
Product Name: regorafenib
Pharmaceutical Form: Tablet
INN or Proposed INN: REGORAFENIB
CAS Number: 755037-03-7
Other descriptive name: REGORAFENIB
Pharmaceutical form of the place
Sponsors
Centre Oscar Lambret
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years 2. Histologically proven soft tissue sarcoma including leiomyosarcoma, synovial sarcoma and other sarcomas (confirmation of diagnosis by expert pathologist from the RRePS network) 3. Patients in partial response or stable disease after 6 cycles of doxorubicin-based first-line chemotherapy for metastatic/locally advanced soft tissue sarcoma 4. Metastatic/locally advanced disease not amenable to surgical resection with curative intent 5. Eastern Cooperative Oncology Group (ECOG) Performance Status =0 or 1 6. Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST 1.1. 7. Available tumor tissue for translational research program 8. Adequate bone marrow, renal, and hepatic function, as evidenced by the following tests performed within 7 days of study treatment initiation: - Absolute neutrophil count (ANC) =1,500/mm3 - Platelets =100,000/mm3 - Hemoglobin =9.0 g/dL - Serum creatinine =1.5 x upper limit of normal (ULN) - Glomerular filtration rate (GFR) =30 mL/min/1.73m2 - AST and ALT =2.5 x ULN (=5.0 × ULN for patients with liver involvement of their cancer) - Bilirubin =1.5 X ULN - Alkaline phosphatase =2.5 x ULN (=5 x ULN with liver involvement of their cancer) - Amylase and/or lipase =1.5 x ULN 9. Spot urine must not show 1+ or more protein in urine or the patient will require a repeat urine analysis. If repeated urine analysis 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 26
Exclusion criteria
Exclusion criteria: 1. Prior adjuvant or neoadjuvant chemotherapy not allowing at least 6 cycles of doxorubicin-based chemotherapy at metastatic stage 2. Complete response to 1st line chemotherapy 3. Disease progression during the 1st line of chemotherapy 4. Time interval between the last cycle of doxorubicin-based chemotherapy superior to 8 weeks 5. Primary bone sarcoma 6. All forms of liposarcoma 7. Some particular histologic types, i.e., PNET/Ewing, alveolar or embryonal rhabdomyosarcoma, Perivascular epithelioid cell sarcoma (PEComa), low grade endometrial stromal tumor, desmoid tumor 8. Prior treatment with tyrosine kinase inhibitor 9. Known history of or concomitant malignancy likely to affect life expectancy in the judgment of the investigator 10. Pregnant or breastfeeding patients. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment 11. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of Day 1 of treatment 12. 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) 13. Uncontrolled hypertension (Systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg despite optimal medical management) 14. Arterial or venous thrombotic or embolic events such as myocardial infarction, cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months of starting on study drug 15. Any hemorrhage or bleeding event > Grade 4 within 4 weeks of start of treatment 16. Ongoing infection >Grade 2 according to NCI Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v. 5.0) 17. Known history of human immunodeficiency virus (HIV) infection 18. Known history of chronic hepatitis B or C 19. Patients with seizure disorder requiring medication 20. History of organ allograft 21. Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event > Grade 4 within 4 weeks of start of treatment 22. Non-healing wound, ulcer, or bone fracture 23. Renal failure requiring hemo- or peritoneal dialysis 24. Dehydration according to NCI-CTCAE v. 5.0 Grade >1 25. Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results 26. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation 27. Interstitial lung disease with ongoing signs and symptoms at the time of informed consent 28. Inability to swallow oral medications, Any mal-absorption condition 29. Pleural effusion or ascites that causes respiratory compromise (Grade 2 dyspnea)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal objective of the trial is to assess the efficacy, in terms of PFS, of regorafenib compared to placebo as maintenance therapy in metastatic soft-tissue, non-adipocytic sarcomas experiencing stable disease or partial tumor response after 6 cycles of doxorubicin-based chemotherapy as 1st line chemotherapy;Secondary Objective: • To assess the efficacy of regorafenib compared to placebo in terms of overall survival, best response, and time to start subsequent line of anticancer therapy • To assess the safety of regorafenib compared to placebo • To assess the relative benefit/risk ratio using the Q-TWiST approach ;Primary end point(s): progression-free survival according to RECIST 1.1 ;Timepoint(s) of evaluation of this end point: From date of randomization until the date of first documented progression or date of death from any cause | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Overall survival, defined as the time interval from the date of randomization to the date death from any cause. Patient data will be censored at the date of last follow-up visit for patients alive at last follow-up visit. 2) Overall best response according to RECIST 1.1 evaluated by central radiological review: Complete Response, CR, or Partial Response, PR achieved during the maintenance therapy 3) Time to start a further cancer therapy 4) Safety and toxicity according to NCI-CTC AE V4 5) Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) 6) Additional exploratory objective, this Phase II trial will be used with the aim of assessing the predictive value of SUMSCAN signature (genomic signature established on initial diagnostic biopsies or resection specimen and identifying sarcoma patients benefitting from anti-angiogenetic agents) ;Timepoint(s) of evaluation of this end point: From date of randomization until the date of first documented progression or date of death from any cause | — |
Countries
France
Contacts
Public ContactSponsor unit
Centre Oscar lambret
Outcome results
None listed