NCT06044311

Oral TGF-beta Receptor I Inhibitor Vactosertib in SOC Chemoradiotherapy for Esophageal Adenocarcinoma

A Window of Opportunity Trial Evaluating the Oral TGF-beta Receptor I Inhibitor Vactosertib in Patients Undergoing Standard of Care Chemoradiotherapy for Locally Advanced Esophageal Adenocarcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Sakti Chakrabarti · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This interventional clinical trial aims to find ways of improving treatments for individuals with esophageal cancer. Laboratory-based studies show that using medicines that affect a protein called TGF-beta (TGFβ) can kill esophageal cancer cells in individuals who have localized esophageal adenocarcinoma and are being considered for standard-of-care chemoradiation prior to surgery. Participants of this study will take a pill called vactosertib for two weeks before starting standard of care chemoradiation. At the end of the two weeks of taking vactosertib, participants will have a Positron Emission Tomography Computer Assisted Tomography (PET CT) scan and undergo an endoscopy with a biopsy to determine if the vactosertib is working. After chemoradiation, participants will take vactosertib again for four weeks and then be considered for surgery.

Detailed description

Esophageal adenocarcinoma (EAC) is an aggressive malignancy with limited effective treatment options. In localized EAC (clinical stages II and III), the standard of care is pre-operative concurrent chemoradiation (CRT) followed by surgical resection, which results in pathologic complete response (pCR) in approximately 20% of participants, but with high rates of post-operative recurrence. It was recently discovered that EACs are driven by signaling through TGFβ Receptor I (TGFβRI), and in vivo models of EAC show tumor reduction by targeting this pathway with a novel small molecule inhibitor of TGFβRI called vactosertib. In this study, participants who have locally advanced EAC will be treated with vactosertib before and after standard of care chemoradiation to take advantage of natural windows of opportunity during which participants are being planned for their standard of care treatments.

Conditions

• Adenocarcinoma Esophagus
• Locally Advanced Adenocarcinoma
• Siewert Type I Adenocarcinoma of Esophagogastric Junction
• Siewert Type II Adenocarcinoma of Esophagogastric Junction

Interventions

Type	Name	Description
DRUG	Vactosertib	200 mg orally, twice daily for five days a week, for 2 weeks and again for 4 weeks after chemoradiotherapy.
DRUG	Standard of Care Chemotherapy	Neoadjuvant chemotherapy treatment as per standard of care.
RADIATION	Concurrent Radiation	Neoadjuvant radiation treatment as per standard of care.

Timeline

• Start date: 2024-09-30
• Primary completion: 2026-12-31
• Completion: 2027-06-01
• First posted: 2023-09-21
• Last updated: 2025-02-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study