A Study to Evaluate the Safety and Efficacy of Vactosertib and Imatinib in Patients With Advanced Desmoid Tumor
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|ClinicalTrials.gov Identifier: NCT03802084|
Recruitment Status : Recruiting
First Posted : January 14, 2019
Last Update Posted : January 14, 2020
|Condition or disease||Intervention/treatment||Phase|
|Desmoid Tumor||Drug: vactosertib/imatinib combination||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b/2a, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib in Combination With Imatinib in Patients With Advanced Desmoid Tumor (Aggressive Fibromatosis)|
|Actual Study Start Date :||April 15, 2019|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2020|
|Experimental: vactosertib/imatinib combination||
Drug: vactosertib/imatinib combination
Phase 1 : Imatinib 400mg QD P q28days Vactosertib 1 cohort 200mg bid (D1-5, 8-12, 15-19, 22-26)
- adverse event [ Time Frame: 4 weeks ]to evaluate the safety and tolerability
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03802084
|Contact: Hyo Song Kim, Ph.Dfirstname.lastname@example.org|
|Korea, Republic of|
|Severance Hospital, Yonsei University Health System||Recruiting|
|Seoul, Korea, Republic of, 03722|
|Contact: Hyo Song Kim 82-2-2228-8124 email@example.com|