Melissa Lumish
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 therapy. 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 standard of care therapy, participants will take vactosertib again for two 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…
Inclusion Criteria: * Subjects must have histologically or cytologically confirmed poorly differentiated or Grade 3 adenocarcinoma of the esophagus or gastroesophageal junction, clinical stage II or III and must be appropriate for standard of care preoperative therapy with concurrent chemoradiotherapy with carboplatin and paclitaxel or FOLFOX OR with FLOT +/- durvalumab as per standard of care. Clinical staging appropriate: * cT2 N0 with high-risk lesions including lymphovascular invasion, tumors ≥ 3cm in size, or poorly differentiated histology, or * cT1b-cT2, N+, or * cT3-cT4a, any N…
300 mg orally, twice daily for five days a week, for 2 weeks and again for 2 weeks after completion of preoperative therapy.
Preoperative therapy will NOT be determined by the clinical trial protocol. It will be determined per standard of care by the treating physician and participant. Preoperative therapy will either be FLOT for 8 weeks OR concurrent radiation and chemotherapy (carboplatin and paclitaxel or FOLFOX) for 5-6 weeks, per standard of care.