Neoplasms

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Digestive System Diseases

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Adenocarcinoma

Esophageal Neoplasms

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Gastrointestinal Neoplasms

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Gastrointestinal Diseases

Esophageal Diseases

Camurati-Engelmann Disease

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Vactosertib

Protein Kinase Inhibitors

Enzyme Inhibitors

Vactosertib orally, 200 mg twice daily for five days a week for 2 weeks, followed by standard of care chemoradiotherapy, followed by Vactosertib for 4 weeks after standard of care chemoradiotherapy

200 mg orally, twice daily for five days a week, for 2 weeks and again for 4 weeks after chemoradiotherapy.

Neoadjuvant chemotherapy treatment as per standard of care.

Standard of Care Chemotherapy

Neoadjuvant radiation treatment as per standard of care.

Concurrent Radiation

Jennifer E Selfridge, MD, PhD

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.

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.

This study is a phase 2, single-arm, Simon two-stage design. 15 participants will be enrolled in the first stage, with the potential of expanding to an additional 10 participants.

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

Determine if two-week treatment with single agent vactosertib induces metabolic response by PET CT imaging in primary EAC tumors. This will be measured as the rate of tumors that have decreased FDG tracer uptake by \>= 35% SUV on PET CT after 2 week treatment with vactosertib.

Evaluate the pathological response at the time of surgery after the combination therapy of CRT followed by vactosertib in patients with locally advanced EAC. This will be defined by the rate of pathological complete response at the time of surgical resection.

Correlate baseline expression of HNF4A with clinical response to vactosertib. HNF4A expression will be measured by immunohistochemistry and positive or negative expression will be correlated with rate of pathological complete response and metabolic response.

Determine if oral vactosertib is feasible in treatment of locally advanced EAC prior to and after CRT. Feasibility will be measured as the rate of patients able to complete \>= 75% of planned doses of vactosertib.

Spots Global Cancer Trial Database for locally advanced adenocarcinoma