Phase II study of regorafenib as salvage therapy in metastatic soft tissue sarcoma
- Conditions
- Metastatic soft tissue sarcomaMedDRA version: 15.1Level: HLGTClassification code 10041299Term: Soft tissue sarcomasSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-005743-24-AT
- Lead Sponsor
- Centre Oscar Lambret
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 192
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 <1000 mg/24 hours
9. INR/PTT =1.5 x ULN
10. Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care.
11. Women of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 3 months following completion of therapy. Adequate contraception is defined as any medically recommended method (or combination of methods) as per standard of care.
12. Recovery to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure related toxicity (except alopecia, anemia, and hypothyroidism).
13. In the assessment of the investigator, patient is able to comply with study requirements
14. Signed, IRB-approved written informed consent
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 192
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 192
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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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<br>- To explore the growth modulation index in patients receiving regorafenib after randomization <br>- To evaluate toxicity according to NCI-CTC AE V4.0. <br>Exploratory<br>- 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 Outcome Measures
Name Time Method 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<br>2. Toxicity according to NCI-CTC AE V4.0<br>3. Growth modulation index<br>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. <br>;Timepoint(s) of evaluation of this end point: 1. 3 to 6 months<br>2. LVLS<br>3. Disease progression<br>