Adenocarcinoma EsophagusPhase 2NCT06044311
Oral TGF-beta Receptor I Inhibitor Vactosertib in SOC Chemoradiotherapy for Esophageal Adenocarcinoma
A Phase 2 study testing Vactosertib in people with Adenocarcinoma Esophagus and Locally Advanced Adenocarcinoma, run by Melissa Lumish at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma Esophagus, Locally Advanced Adenocarcinoma, Siewert Type I Adenocarcinoma of Esophagogastric Junction
- What is being tested?
- Vactosertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2024to Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Melissa Lumish, MD, 216-844-3951, CTUGIMedOncTeam@UHhospitals.org
About this study
Official title: 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 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.
Read the detailed description
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.
- Conditions
- Adenocarcinoma Esophagus, Locally Advanced Adenocarcinoma, Siewert Type I Adenocarcinoma of Esophagogastric Junction, Siewert Type II Adenocarcinoma of Esophagogastric Junction
- Being tested
- Vactosertib, Standard of Care Preoperative Therapy
- Medical subject headings
- Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VactosertibDrug
Also called Oral TGF-beta Receptor I Inhibitor
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 TherapyDrug
Also called Carboplatin, Paciltaxel, FLOT, FOLFOX
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.
| Study group | Role | What they receive |
|---|---|---|
| Vactosertib + Preoperative therapy | Experimental | Vactosertib orally, 300 mg twice daily for five days a week for 2 weeks, followed by standard of care preoperative therapy, followed by Vactosertib for 2 weeks after standard of care preoperative therapy Receives: Drug: Vactosertib; Drug: Standard of Care Preoperative Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At two weeks post treatment
Secondary outcomes (3)
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.
Measured: At approximately 14 weeks from starting treatment
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.
Measured: At approximately 14 weeks from starting treatment
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.
Measured: At approximately 14 weeks from starting treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start30 Sep 2024
- Primary completionMar 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adenocarcinoma EsophagusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Melissa Lumish
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Melissa Lumish, Case Comprehensive Cancer Center
- Investigators
- Melissa Lumish, MD, Principal investigator, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06044311
- Sponsor's protocol ID
- CASE1223
- Status last verified
- Sep 2026
- First submitted
- 7 Sep 2023
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06044311
- Acronym / sponsor ID
- CASE1223
- Conditions
- Adenocarcinoma Esophagus, Locally Advanced Adenocarcinoma, Siewert Type I Adenocarcinoma of Esophagogastric Junction, Siewert Type II Adenocarcinoma of Esophagogastric Junction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Melissa LumishUniversity, hospital or other
- Study start
- 30 Sep 2024 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 21 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Vactosertib + Preoperative therapy | Experimental | Drug: Vactosertib, Drug: Standard of Care Preoperative TherapyVactosertib orally, 300 mg twice daily for five days a week for 2 weeks, followed by standard of care preoperative therapy, followed by Vactosertib for 2 weeks after standard of care preoperative therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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:
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VactosertibAlso: Oral TGF-beta Receptor I Inhibitor300 mg orally, twice daily for five days a week, for 2 weeks and again for 2 weeks after completion of preoperative therapy. | Drug | Vactosertib + Preoperative therapy |
| Standard of Care Preoperative TherapyAlso: Carboplatin, Paciltaxel, FLOT, FOLFOXPreoperative 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. | Drug | Vactosertib + Preoperative therapy |
Primary outcome
Metabolic Response
Time frame: At two weeks post treatment
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.
3 secondary outcomes
Pathological Response
Time frame: At approximately 14 weeks from starting treatment
Correlate baseline expression
Time frame: At approximately 14 weeks from starting treatment
Ability to take vactosertib before and after standard of care therapy
Time frame: At approximately 14 weeks from starting treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Melissa Lumish, MD principal investigator
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vactosertib in people with Adenocarcinoma Esophagus and Locally Advanced Adenocarcinoma, run by Melissa Lumish at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Melissa Lumish, MD (216-844-3951, Melissa.Lumish@uhhospitals.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolic Response (time frame: At two weeks post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.