Study to Assess Safety and Efficacy of Vactosertib in Adolescents and Adults With Recurrent, Refractory or Progressive Osteosarcoma

NCT05588648 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MP-VAC-209
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 3

Brief Summary

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 12 years of age and older who meet the criteria for study enrollment.

Conditions

Osteosarcoma

Outcome Measures

Primary Outcomes (1)

• Dose finding associated with the overall nature and severity of AEs associated with treatment.

  Maximum tolerated dose (MTD) and recommended dose (RD)

  Assessment of adverse events and laboratory abnormalities. through study completion, an average of 1 year

Secondary Outcomes (2)

• Overall survival.

  Acquiring the measures associated with phase I/phase II primary endpoints.

• Time to response(TTR)

  Post two cycle of treatment, evaluation. through study completion, an average of 1 year.

Study Arms (1)

Single Arm

EXPERIMENTAL

Single arm, open-label, no blinding or randomization procedure will be involved.

Drug: Vactosertib

Interventions

Vactosertib DRUG

Vactosertib is given twice a day, five days on and two days off in four-week cycles. Vactosertib is a transforming growth factor-beta (TGF-β) type 1 receptor inhibitor.

Also known as: TEW-7197

Single Arm

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent/Assent Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Age ≥12 years at the time of screening
• Type of Subject and Disease Characteristics
• Subjects may be male or female and must be equal to or greater than 12 years of age. No large studies have evaluated the use of vactosertib in younger pediatric subjects, for this reason, children younger than 12 years of age are excluded from this study.
• Subjects must have histologic verification of Osteosarcoma (OS)
• Subjects must have measurable disease per RECIST 1.1 (Appendix C), documented by clinical, radiographic and histologic criteria, and have progressed, relapsed or become refractory to conventional therapy.
• Subjects must have recovered from the acute toxic effects with ≤ Grade 1 as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 of all prior chemotherapy and immunotherapy with the exception of alopecia, anorexia, bone pain, and tumor pain prior to entering this study.
• Myelosuppressive chemotherapy: Must have adequate recovery of counts from previous treatment prior to entry onto this study.
• Subjects must have normal organ and marrow function as defined below:
• a. Adequate bone marrow function defined as: i. Peripheral absolute neutrophil count (ANC) ≥ 750/mcL ii. Platelet count ≥ 75,000/mcL (transfusion independent) iii. Hemoglobin ≥ 8.0 g/dL (may receive packed red blood cell transfusions) b. Adequate liver function defined as: i. Total bilirubin ≤ 1.5 times the upper limit of normal for age ii. AST (SGOT) and ALT (SGPT) 2.5 X institutional upper limit of normal iii. Albumin (serum or plasma) \> 2 g/dL c. Adequate cardiac function defined as: i. Ejection fraction of ≥ 50% by echocardiogram or MUGA
• Subjects must have the ability to understand and the willingness to sign a written informed consent document if ≥ 18 years of age and an assent document if \< 18 years of age (per country).
• Relapsed osteosarcoma (first, second, third or any relapse, subject who have recovered from chemotherapy and any other investigational drug/agent treatment, radiotherapy or surgical procedure), with histological confirmed diagnosis of osteosarcoma at original presentation, and progressive disease documented by imaging within 3 months of entry into the trial.

You may not qualify if:

• The subject must be excluded from participating in the trial if:
• Subjects who have moderate or severe cardiovascular disease
• Subjects who have uncontrolled intercurrent illness, including but not limited to, ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure (New York Heart Association Class III/IV), uncontrolled hypertension (≥150/90mmHg), unstable angina pectoris or myocardial infarction (≤ 6 months prior to screening), uncontrolled cardiac arrhythmia, clinically significant cardiac valvulopathy requiring treatment, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent
• Subjects who have major abnormalities at the Investigator's discretion based on electrocardiogram (ECG)and Doppler ECHO and MUGA results at screening or within 14 days before screening. QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms in both male and female calculated from 12-lead ECGs.
• Subjects who have increase in brain natriuretic peptide (BNP) or increase in troponin (over 99th percentile upper reference limit) at Screening (based on the normal range of relevant study center)
• Subjects who have risk factors for ascending aortic aneurysm such as genetic disorder and trauma and risk factors for aortic stenosis
• Subjects who have a history of heart or aorta surgery
• Subjects who have clinically significant gastrointestinal bleeding within 4 weeks before screening
• Subjects who have a known history or suspected hypersensitivity to any excipients of the investigational product.
• Subjects who have received prior treatment targeting the signaling pathway of TGF-β
• Subjects who have a disease or condition that affects the mechanism of the investigational product, or are currently using or planning to use:
• Drugs that are exclusively or primarily eliminated by cytochrome P-450 isozyme (CYP) including CYP1A2, CYP2D6, CYP2B6, or CYP3A4 (Concurrent use of drugs that are known potent CYP3A4 inducers including but not limited to Phenytoin, Rifampin, and St. John's wort. Concurrent use of foods that are known strong CYP3A4 inhibitors including but not limited to grapefruit juice, Itraconazole, Ketoconazole, Lopinavir/ritonavir, Mibefradil, and Voriconazole. The topical use of these medications (if applicable), such as 2% ketoconazole cream, may be allowed.)
• Drugs that are exclusively or primarily eliminated by UDP glucuronyltransferase (UGT) 1A1 (UGT1A1)
• Drugs that are substrates for the drug transporter multidrug resistance protein 1 (MDR1) have a narrow therapeutic window or are strong inhibitors of drug transporter MDR1
• Subjects who are unable to swallow tablets

Sponsors & Collaborators

• MedPacto, Inc.: lead

Study Sites (3)

UH Rainbow Babies & Children's Hospital

Cleveland, Ohio, 44106, United States

RECRUITING

National Cancer Center

Gyeonggi-do, South Korea

RECRUITING

Korea Institute of Radiological & Medical Sciences

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Osteosarcoma

Interventions

vactosertib

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Central Study Contacts

Kristen VanHeyst, DO

CONTACT

(216) 844-3345; Kristen.VanHeyst@UHhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: October 20, 2022
• Study Start: May 1, 2023
• Primary Completion: September 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 10, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); KR (2)