Those studies demonstrate strong rationale to combine a multikinase inhibitor targeting VEGFR, PDGFR with mTOR inhibitor. Moreover, another multi-targeted TKI, lenvatinib monotherapy showed promising activity in osteosarcoma. Therefore, clinical trial with Lenvatinib in combined with everolimus is ongoing for solid tumors (NCT03245151). Considering lenvatinib and everolimus (18 mg/day and 5 mg/day) already approved as standard treatment for renal cell carcinoma based on the powerful ORR, PFS, and OS14, these noteworthy findings advance the treatment paradigm for bone sarcoma patients. Because all those trials for sarcoma were done in the absence of a control group, based on such clinical studies, a confirmatory trial comparing mTOR inhibitor and a multi-targeted tyrosine kinase inhibitor (multi-TKI) combination versus monotherapy is essential. Therefore, we planned to conduct the randomized phase II trial of everolimus in combination with lenvatinib for advanced/metastatic bone sarcomas. In addition, we will explore predictive biomarkers by repeated biopsies and blood samplings during the treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
94
Everolimus (5 mg) and Lenvatinib (14 mg) will be administered orally once daily (QD) in continuous 28-day cycles. In subjects who maintain toxicity at Grade ≤2 during the initial 4-week period (Cycle 1), the Lenvatinib dose may be escalated to 18 mg QD beginning in Cycle 2, at the discretion of the investigator
Everolimus (10 mg) will be administered orally once daily (QD) as monotherapy in continuous 28-day cycles. Upon radiologic or clinical disease progression, subjects may switch to Lenvatinib (24 mg) monotherapy, administered orally once daily (QD) in 28-day cycles.
Progression free rate (PFR6)
Progression free rate (PFR-6) at 24 weeks will be based on RECIST version 1.1
Time frame: up to 3 years
Progression-free survival (PFS)
The earlier of the date of first documented progressive disease or death from the date of enrollment
Time frame: up to 3 years
Overall survival (OS)
From the date of treatment initiation to the date of death or last follow-up
Time frame: up to 3 years
Number of participants with treatment-related adverse events
Number of participants with treatment-related adverse events: Adverse events considered related to study treatment will be assessed according to CTCAE version 5.0.
Time frame: up to 3 years
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