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• Register: EUCTR
• Last refreshed on: 7 September 2015
• Main ID: EUCTR2013-003910-42-FR
• Date of registration: 24/08/2015
• Prospective Registration: No
• Primary sponsor: UNICANCER
• Public title: _
• Scientific title: A Randomized Phase II, placebo-controlled , multicenter study evaluating efficacy and safety of regorafenib in patients with metastatic bone sarcomas. - REGOBONE
• Date of first enrolment: 06/05/2014
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003910-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

France

Contacts

• Name: Karine BUFFARD, Project Manager
• Affiliation: UNICANCER

• Name: Karine BUFFARD, Project Manager
• Affiliation: UNICANCER

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients must have histologically confirmed diagnosis of bone sarcoma (osteosarcoma, Ewing sarcoma of bone, chondrosarcoma) with available Formalin Fixed Paraffin Embedded (FFPE) blocks obtained for centralized review;
2. Patients with confirmed disease progression at study entry. The “baseline” radiological evaluation should demonstrate disease progression by RECIST V 1.1 when compared to a prior disease assessment done within a prior period of 3 month for osteosarcoma and Ewing sarcomas and within 6 month period for chondrosarcomas prior to screening
Note: radiographic progression of disease will be based on at least 2 sets of scans (either MRI or CT) in the 3-month (for osteosarcomas and Ewing sarcoma) or 6-month period for chondrosarcoma prior to or during screening in which radiographic progression of disease , as defined by RECIST , is demonstrated. No central review of scans (either MRIs or CTs) will be required for study eligibility; these scans must be sent for central review within 10 days after randomization;
3. Metastatic disease not amenable to surgical resection or radiation with curative intent;
4. Patients must have measurable disease (outside any previous irradiated field) defined as at least one unidimensionally lesion that can be accurately measured as = 10 mm with CT scan according to RECIST V1.1;
5. Prior treatment :
at least one, but no more than two prior (combination) chemotherapy regimen for metastatic disease; neo-adjuvant /maintenance therapy are not counted towards this requirement. At least 4 weeks since last chemotherapy (6 weeks in case of nitrosoureas and mitomycin C), immunotherapy or any other pharmacological treatment and/or radiotherapy;
6. Age = 18 years;
7. Life expectancy of greater than 3 months;
8. ECOG performance status < 2 (Karnofsky = 60%);
9. Patients must have adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation : normal organ function as defined below :
a. Absolute neutrophil count = 1.5 Giga/L
b. Platelets = 100 Giga/L
c. Hemoglobin= 9 d/dL
d. Serum creatinin = 1.5 x ULN
e. Glomerular filtration rate (GFR) =30 ml/min/1.73m2 according to the modified Diet in Renal Disease (MDRD) abbreviated formula
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 or 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 urinalysis shows 1+ protein or more, a 24-hour urine collection will be required and must show total protein excretion <1000 mg/24 hours
10. INR/PTT =1.5 x ULN;
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. 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);
12. Women of childbearing potent
Exclusion criteria:
1. Prior treatment with any VEGFR inhibitor (thus, any prior exposure to sunitinib, sorafenib, pazopanib, bevacizumab, or other VEGFR inhibitor would render the patient ineligible for this study);
2. Low grade histological subtypes: low grade chondrosarcomas, low grade osteosarcoma, paraosteal/periosteal osteosarcoma;
3. Soft tissue sarcoma (including Ewing soft tissue sarcoma);
4. Other cancer (different histology) within 5 years prior to randomization;
5. Major surgical procedure, open biopsy, significant trauma, within the last 28 days before randomization;
6. Cardiovascular dysfunction:
- Congestive heart failure (New York Heart Association [NYAH]) = 2,
- Myocardial infarction <6 months before study
- Cardiac arrhythmias requiring therapy (beta blockers or digoxin are permitted)
- Uncontrolled hypertension (systolic blood pressure > 150mmHg or diastolic pressure > 90mmHg despite optimal treatment)
- Unstable (angina symptoms at rest) or new-onset angina (begun within the last 3 months);
7. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the last 6 months before randomization;
8. Severe hepatic impairment (Child-Pugh C);
9. Ongoing infection > Grade 2 according to NCI-CTCAE v4.0;
10. Known history of human immunodeficiency virus (HIV) infection;
11. Known history of chronic hepatitis B or C;
12. Difficulties with swallowing study tablets;
13. Prior anticancer therapy, including radiotherapy, endocrine therapy, immunotherapy, chemotherapy (CT) within the last 4 weeks (6 weeks for nitrosoureas and mitomycin C), or other investigational agents ; Concomitant antalgic palliative radiotherapy allowed.
14. Concurrent enrolment in another clinical trial in which investigational therapies are administered;
15. Known hypersensitivity to the active substance or to any of the excipients;
16. Pregnant women, women who are likely to become pregnant or are breast-feeding;
17. Individual deprived of liberty or placed under the authority of a tutor;
18. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
19. Patients with history of non compliance to medical regimens or unwilling or unable to comply with the protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Metastatic bone sarcomas: conventional high grade osteosarcoma, Ewing sarcoma of bone, intermediate or high-grade chondrosarcomas.
MedDRA version: 17.0 Level: PT Classification code 10008736 Term: Chondrosarcoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0 Level: PT Classification code 10015562 Term: Ewing's sarcoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0 Level: PT Classification code 10031294 Term: Osteosarcoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: STIVARGA
Pharmaceutical Form: Coated tablet
INN or Proposed INN: REGORAFENIB
Current Sponsor code: REGORAFENIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: _

Primary end point(s): The primary efficacy endpoint is PFS [defined using RECIST 1.1] after central radiological review Progression-Free Survival will be measured from the date of randomization until the date of radiological progression or death whatever the cause (if death occurs before progression).

Main Objective: The principal objective of the trial is to investigate the antitumor activity of regorafenib in terms of progression Free Survival (PFS) according to modified RECIST (RECIST 1.1) after central radiological review.

Secondary Objective: 1. Objective response rate [defined as complete response (CR) or partial response according to RECIST 2009, version 1.1] ;
2. Disease control rate at 6 months (defined as the proportion of patients who a best response rating of CR, PR or stable disease [SD]), SD should be at least 8 weeks ;
3. Overall survival (defined as the time from the date of randomization until the date of death due to any cause); if the patients is alive at the date of data base cut off then he will be censored at the data base cut off date;
4.Duration of response (defined as the time from date of first documented objective response of CR or PR, whichever is noted earlier, to first disease progression or death before progression ;

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: _

Secondary end point(s): 1. Objective response rate [defined as complete response (CR) or partial response (PR) according to RECIST 2009, version 1.1] ;
2. Disease control rate at 6 months (defined as the proportion of patients who a best response rating of CR, PR or stable disease [SD]), SD should be at least 8 weeks ;
3. Overall survival (defined as the time from the date of randomization until the date of death due to any cause); if the patients is alive at the date of data base cut off then he will be censored at the data base cut off date;
4. Duration of response (defined as the time from date of first documented objective response of CR or PR, whichever is noted earlier, to first disease progression or death before progression ;
5. Progression-free rate at 3 and 6 months (PFR-3 and PFR-6), defined as the proportion of patients without progression at 3 and 6 months post randomization;
6. Time to progression (measured from date of randomization until the date of first observation of progression );
7. Growth Modulation Index defined as ratio of time to PD under regorafenib to TTP under previous treatment. The GMI will be explored in patients receiving regarafenib after randomization.
8. Identification and characterization of biomarkers
Toxicity according to NCI-CTC V4.0.

Secondary ID(s)

UC-0150/1309_SARCOME_12

Source(s) of Monetary Support

BAYER HealthCare AG