Overall Design:~This is a Phase I/II, open label, single arm, proof of concept, multi-center study to assess safety, tolerability, pharmacokinetics and antitumor activity of vactosertib as a Single Agent in Adolescents and Adults with Recurrent, Refractory or Progressive Osteosarcoma. During the Phase I part of the trial, dose limiting toxicity will be determined by a standard 3+3 dose escalation design. Data from the Phase I part of the trial will be reviewed by the Data Safety and Toxicity Committee before transitioning to Phase II. During Phase I, at least 6 patients will be enrolled at the maximum tolerated dose (MTD) level. To evaluate efficacy during Phase II, 42 patients will be enrolled at the maximum dose level; this includes the patients enrolled at this dose level during Phase I.~This study has been designed to allow for an investigation of the optimal dose of vactosertib. This clinical study consists of two parts:~Phase I: Vactosertib dose-escalation study: To determine the recommended phase II dose (RP2D) and evaluate the safety and tolerability of vactosertib in subjects with recurrent, refractory, or progressive OS; and~● Initially, the dose limiting toxicity and maximum tolerated dose (MTD) of vactosertib in adolescence and young adult age population (14 and older) will be evaluated using a standard 3 + 3 design for adult equivalent doses of 150 mg BID, 5 days on and two days off, 200 mg BID, five days on and two days off and 250 mg, BID, five days on and two days off for one week.~Phase I/II: Vactosertib PK/PD and efficacy study: to characterize the pharmacokinetics (PK) of vactosertib and to determine the efficacy of vactosertib by evaluating the antitumor activity of vactosertib, the overall response rate of subjects treated with vactosertib and by assessing the effect of vactosertib on Pharmacodynamic (PD) biomarkers on baseline and serial tumor tissues and blood samples.~● Once the safety and MTD of vactosertib in adolescence and young adult age population (14 and older) is established, the study will then enroll a total of 42 evaluable patients, including the patients enrolled at MTD level during Phase I with the following treatment regimen:~o Vactosertib twice a day, five days on and two days off in a four-week cycle with confirmed treatment dose as per run in (phase I).~Number of patients: Phase I: At least 6 and Phase II: 42~Treatments and Treatment Duration:~Vactosertib will be administered orally 5 days per week (5D/W) approximately at the same time twice daily (BID; morning and evening approximately 12 hours apart). Vactosertib should be taken orally with food.
MP-VAC-209 is a Phase I/II, open label, single arm, multi-center study to assess safety, tolerability, and antitumor activity of vactosertib as a single agent in adolescents and adults with recurrent, refractory, or progressive osteosarcoma. Vactosertib is given orally, twice a day, to people 14 years of age and older who meet the criteria for study enrollment.