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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• 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
• 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 vactosertib in subjects ≤18 years of age, children are excluded from this study.
• ECOG Performance status ≤2
• Subjects must have adequate 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 chemotherapy as per standard of care
• Subjects must have no contraindication to receiving radiation as per standard of care, unless the standard of care plan is to receive peri-operative FLOT +/- durvalumab
• 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

You cannot join if

• 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
• Subjects with contraindication to the planned chemotherapy medications (FLOT = fluorouracil, oxaliplatin, docetaxel) or the planned chemoradiation medications (carboplatin and paclitaxel or fluorouracil and oxaliplatin) as per standard of care
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding women are excluded from this study because cytotoxic agents and radiation therapy have the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued if the mother participates in the trial. These potential risks may also apply to other agents used in this study
• HIV-positive patients are ineligible because of the potential for pharmacokinetic interactions with chemotherapeutic agents and because of a potential risk of worsening HIV viral load in response to TGFβ signaling inhibition. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy
• Chronic active untreated hepatitis B or C infection. (Assessments should include Hepatitis B Surface AB, Hepatitis B Surface AG, Hepatitis B Core AB - Total, Hepatitis B Core AB, IGM, Hepatitis C AB)
• Treated viral hepatitis patients with undetectable viral load are excluded because there is an enhanced risk of reactivation of the virus. Apart from the potential reactivation risk, the hepatitis-induced liver damage may delay or even cause discontinuation of chemotherapy
• Viral hepatitis patients receiving antiviral therapy are ineligible because of the potential for pharmacokinetic interactions with chemotherapeutic agents
• Subject who is taking prohibited medications when using vactosertib. A minimal washout period of 5 half-lives for the following drugs is recommended prior to the first dosing
• Concurrent use of drugs or foods that are known strong CYP3A4 inhibitors including but not limited to grapefruit juice, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, voriconazole. The topical use of these medications (if applicable), such as 2% ketoconazole cream, may be allowed
• Concurrent use of drugs that are known potent CYP3A4 inducers including but not limited to phenytoin, rifampin, St. John's wort
• Concurrent use of drugs that are CYP3A4, CYP1A2, CYP2B6 substrates with narrow therapeutic indices including but not limited to theophylline, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, sirolimus, tacrolimus, terfenadine (astemizole, cisapride, and terfenadine have been withdrawn from the US market)
• Concurrent use of drugs that are sensitive CYP3A4, CYP1A2, CYP2B6 substrates including but not limited to efavirenz, darunavir, dasatinib, everolimus, lopinavir, midazolam, sirolimus, ticagrelor
• QTc interval ≥470 ms calculated from 12-lead ECG at baseline.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

Treatments listed in the registry

• Vactosertib (Drug): 300 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 (Drug): 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.

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• surgery: Part of the study plan

Main goals

• Metabolic Response (At two weeks post treatment)

Other goals

• Pathological Response
• Correlate baseline expression
• Ability to take vactosertib before and after standard of care therapy

Planned enrollment: 25 (estimated).

• University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, Ohio

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT06044311

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 4, 2026. Public record; not medical advice.