Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03802084 |
Other study ID # |
4-2018-0807 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 1/Phase 2
|
First received |
|
Last updated |
|
Start date |
April 15, 2019 |
Est. completion date |
March 26, 2024 |
Study information
Verified date |
May 2024 |
Source |
Yonsei University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This is a phase I/II, open-label, non-randomized, multicentre study to evaluate the clinical
activity of vactosertib plus imatinib in desmoid tumor. Based on the background, TGF-β
inhibition as a potential therapeutic target for desmoid tumor and convey significant
implications for the clinical development. Therefore, investigator will conduct the phase II
trial of vactosertib in combined with imatinib in desmoid tumor.
Description:
Desmoid tumor (aggressive fibromatosis) is a mesenchymal neoplasm associated with mutations,
resulting in -catenin-mediated transcriptional activation. It is composed of a clonal
proliferation of mesenchymal, fibroblast-like cells occurred sporadic or as a part of
familial adenomatosis polyposis. This tumor has high local recurrence rate after complete
excision (~40%). Therefore, although lacking metastatic capability, patients experience
repeated recurrence with attendant severe morbidity. Various systemic therapy using NSAID,
cytotoxic agent (doxorubicin and vinblastine), biologic agents (tamoxifen, low-dose
interferon), and tyrosine kinase inhibitors (imatinib) are recommended with modest activity.
Among them, imatinib has shown promising activity and approved as standard treatment for
desmoid tumor. However, still there is modest response (10-15% responses) and further
combination strategy is warranted to improve antitumor efficacy.
The transforming growth factor-β (TGF-β) family of cytokines has 33 members in humans,
including TGF-β isoforms, activins, bone morphogenetic proteins (BMPs), and growth and
differentiation factors (GDFs). These factors regulate growth, survival, differentiation and
migration of cells, and have important roles during embryonal development and in the control
of adult tissue homeostasis. During carcinogenesis, TGF-β has a dual role; initially it
suppresses tumorigenesis by inducing growth arrest and promoting apoptosis, however, in
advanced cancers, where TGF-β often is overexpressed. In addition, TCGA (the cancer genome
atlas) pan-cancer also demonstrated high expression of TGF-β responsive signature in desmoid
tumor. Regarding the combination, TEW-7197 (vactosertib), a TGF-β inhibitor and imatinib
demonstrated synergistic effect in vitro and xenograft model. Compared to imatinib alone,
administration of imatinib plus vactosertib to mice significantly delayed disease relapse and
prolonged survival. Collectively, these results indicate that vactosertib may be a promising
candidate for a new therapeutic strategy.
Based on the background, TGF-β inhibition as a potential therapeutic target for desmoid tumor
and convey significant implications for the clinical development. Therefore, investigator
will conduct the phase II trial of vactosertib in combined with imatinib in desmoid tumor.