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- Conditions
- Metastatic bone sarcomas: conventional high grade osteosarcoma, Ewing sarcoma of bone, intermediate or high-grade chondrosarcomas.MedDRA version: 17.0Level: PTClassification code 10008736Term: Chondrosarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.0Level: PTClassification code 10015562Term: Ewing's sarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 17.0Level: PTClassification code 10031294Term: Osteosarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003910-42-FR
- Lead Sponsor
- ICANCER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method