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
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.
• Subjects must have histologically or cytologically confirmed poorly differentiated or Grade 3 adenocarcinoma of the esophagus or gastroesophageal junction, clinical Stage II or III who are appropriate for concurrent chemoradiotherapy with carboplatin and paclitaxel or FOLFOX 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
• Subjects must be deemed a potential surgical candidate by a thoracic surgeon, surgical oncologist, or surgeon who is qualified to perform an esophagectomy.
• Subjects must NOT have received prior chemotherapy, immunotherapy, or radiation therapy for management of this malignancy (prior ablations or localized therapies for Barrett's metaplasia are acceptable).
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of vVactosertib in subjects ≤18 years of age, children are excluded from this study.
• ECOG Performance status ≤2
• Subjects must have normal organ and marrow function as defined below:
‣ Serum total bilirubin \<2 mg/dl. If known Gilbert syndrome, total bilirubin must be \<3mg/dl
⁃ AST (SGOT) ≤ 2.5 X institutional upper limit of normal
⁃ ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
⁃ Serum Creatinine ≤ 1.5 X institutional upper limit of normal
⁃ Hemoglobin ≥ 7.5 g/dL
⁃ Absolute neutrophil count ≥ 1,500/mcL
⁃ Platelet count ≥ 100,000/mcL
• Subjects must have no contraindication to receiving recommended concurrent chemotherapy as per standard of care.
• Subjects must have no contraindication to receiving radiation as per standard of care.
• Women of child-bearing potential and sexually active men with female partners of child-bearing potential must agree to abstain from sexual intercourse for the duration of their participation in the study or agree to use highly effective methods of contraception. This is expected for the entire duration of the study period and up to 6 months after the last dose. Highly effective methods of contraception include: female sterilization (tubal ligation, bilateral oophorectomy, and/or hysterectomy); male sterilization (at least 6 months prior to screening); intrauterine device; and oral, injected, or implanted hormonal contraception AND barrier methods of contraception. Women of child-bearing potential must have documented negative pregnancy test prior to start of investigational treatment regimen.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.
• Subjects must be able to swallow oral medication.
• Subjects must be willing to undergo endoscopic biopsy and PET CT on trial.