Study evaluating the efficacy and safety of regorafenib as maintenance therapy after first-line treatment in patients with bone sarcomas
- Conditions
- Patients with bone sarcomas other than Ewing sarcoma or chondrosarcoma or chordoma, who have no residual disease after neoadjuvant chemotherapy, surgery and/or adjuvant chemotherapy.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004045-16-FR
- Lead Sponsor
- Centre Léon Bérard
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 168
I1. Age = 16 years at the day of consenting to the study;
I2. Patients must have histologically confirmed diagnosis of primary bone sarcoma of one of the following histotypes:
• Osteosarcomas (conventional-intramedullary/central high grade, small cell, telangiectatic or high-grade surface osteosarcomas);
• Bone sarcomas other than Ewing sarcoma, chondrosarcoma and chordoma.
I3. Availability of archival Formalin-Fixed Paraffin Embedded (FFPE) block.
I4. Prior treatment for localized or metastatic disease for bone sarcoma must have been completed. It should include:
• Neoadjuvant chemotherapy with documented assessment of histological response,
• Local procedure: Surgery (or radiotherapy if tumour is unresectable)
• Adjuvant chemotherapy (Nota Bene: patients with histotype different from osteosarcoma may not have received adjuvant treatment).
For OS, (excepted head and neck localisations), neoadjuvant and/or adjuvant chemotherapy should include methotrexate-based regimen for patients < 18 years old or anthracycline and cisplatin-based regimen for patients = 18 years old.
For head and neck OS, neoadjuvant and adjuvant chemotherapy should include adriamycin, cisplatin or ifosfamide-based regimen.
For non-OS, neoadjuvant and/or adjuvant chemotherapy should include adriamycine and/or cisplatine-based regimen.
I5. Recovery to NCI-CTCAE v5 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure related toxicity (except alopecia, anaemia, and hypothyroidism);
I6. Interval between the last chemotherapy administration and the date of randomisation: at least 4 weeks but no longer than 2 months;
...See the protocol
Are the trial subjects under 18? yes
Number of subjects for this age range: 68
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
E1. Prior treatment with any VEGFR inhibitor (thus, any prior exposure to sunitinib, sorafenib, pazopanib, bevacizumab, or other VEGFR inhibitor);
E2. All soft tissue sarcomas (including but not limited to soft tissue osteosarcoma and Ewing soft tissue sarcoma), and Ewing sarcoma, chondrosarcoma and chordoma;
E3. Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) within 3 years prior to randomization;
E4. Cardiovascular dysfunction:
• Left ventricular ejection fraction (LVEF) < 50%,
• Congestive heart failure = New York Heart Association (NYHA) class 2,
• Myocardial infarction < 6 months prior to first study drug administration,
• Cardiac arrhythmias requiring therapy (beta blockers or digoxin are permitted),
• Unstable (angina symptoms at rest) or new-onset angina within the last 3 months prior to first study drug administration;
E5. Uncontrolled hypertension (systolic blood pressure > 150mmHg or diastolic pressure > 90 mmHg despite optimal treatment);
E6. 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 the first study drug administration;
...See the protocol
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to compare the antitumor efficacy of regorafenib versus placebo as maintenance treatment in patients with bone sarcomas. ;Secondary Objective: • The Time to Treatment Failure (TTF),<br>• The Overall Survival,<br>• The Quality of Life (EORTC QLQ-C30),<br>• The tolerance profile (NCI-CTC AE version 5),<br>• Compliance to study treatment<br>;Primary end point(s): the Relapse-Free Survival (RFS).;Timepoint(s) of evaluation of this end point: assessment according to the RECISTv1.1.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • the Time to Treatment Failure (TTF),<br>• the Overall Survival,<br>• the Quality of Life (EORTC QLQ-C30),<br>• the tolerance profile (NCI-CTC AE version 5).<br>;Timepoint(s) of evaluation of this end point: • Throughout the study<br>• Each tumor assessment<br>