About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed advanced Osteosarcoma, Ewing sarcoma, Chondrosarcoma with 1-2 prior chemotherapy
Age ≥19 years, <80 years
ECOG performance status of 0-1
Has at least 1 measurable lesion (as defined by Response Evaluation Criteria in Solid Tumors Version 1.1).
Disqualifiers
Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment within 2 weeks prior to entering the study. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
Any previous treatment to lenvatinib or mTOR inhibitor
Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
Major surgical procedure (as defined by the Investigator) within 14 days prior to the first dose of IP ⑤Active or prior documented autoimmune or inflammatory disorders
Trial design
Parallel
Treatments tested in this trial
Everolimus and Lenvatinib
DrugEverolimus (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
DrugEverolimus (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.
Treatment groups
Trial outcomes
Primary outcomes
Progression free rate (PFR6)
Progression free rate (PFR-6) at 24 weeks will be based on RECIST version 1.1
Secondary outcomes
Progression-free survival (PFS)
The earlier of the date of first documented progressive disease or death from the date of enrollment
Overall survival (OS)
From the date of treatment initiation to the date of death or last follow-up
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.
Locations
Sponsors and contacts
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