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.
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 receiving any other investigational agents. Proton-beam radiation is acceptable, if it is considered standard of care in the opinion of the treating radiation oncologist
Subjects with active malignancy within the past 3 years, except if locally curable cancers that have been apparently cured such as non-melanoma cutaneous malignancy, superficial bladder cancer, or carcinoma in situ of the breast or cervix
History of allergic reactions to carboplatin, paclitaxel (if planned for patient as per SOC) or fluorouracil, oxaliplatin, or docetaxel (if planned for patient as per SOC) or vactosertib
Subjects with contraindication to radiation therapy, unless the standard of care plan is to receive peri-operative FLOT
Single group
Vactosertib
Drug300 mg orally, twice daily for five days a week, for 2 weeks and again for 2 weeks after completion of preoperative therapy.
Standard of Care Preoperative Therapy
DrugPreoperative 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.
Metabolic Response
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.
Pathological Response
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
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.
Ability to take vactosertib before and after standard of care therapy
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.
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Melissa Lumish
Lead sponsor
Case Comprehensive Cancer Center
Sponsor institution
