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

NCT06044311 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CASE1223
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Adenocarcinoma Esophagus; Locally Advanced Adenocarcinoma; Siewert Type I Adenocarcinoma of Esophagogastric Junction; Siewert Type II Adenocarcinoma of Esophagogastric Junction

Outcome Measures

Primary Outcomes (1)

• 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.

  At two weeks post treatment

Secondary Outcomes (3)

• Pathological Response

  At approximately 14 weeks from starting treatment

• Correlate baseline expression

  At approximately 14 weeks from starting treatment

• Ability to take vactosertib before and after standard of care chemoradiation

  At approximately 14 weeks from starting treatment

Study Arms (1)

Vactosertib + Chemoradiotherapy

EXPERIMENTAL

Vactosertib orally, 200 mg twice daily for five days a week for 2 weeks, followed by standard of care chemoradiotherapy, followed by Vactosertib for 4 weeks after standard of care chemoradiotherapy

Drug: Vactosertib; Drug: Standard of Care Chemotherapy; Radiation: Concurrent Radiation

Interventions

Vactosertib DRUG

200 mg orally, twice daily for five days a week, for 2 weeks and again for 4 weeks after chemoradiotherapy.

Also known as: Oral TGF-beta Receptor I Inhibitor

Vactosertib + Chemoradiotherapy

Standard of Care Chemotherapy DRUG

Neoadjuvant chemotherapy treatment as per standard of care.

Also known as: Carboplatin, Paciltaxel

Vactosertib + Chemoradiotherapy

Concurrent Radiation RADIATION

Neoadjuvant radiation treatment as per standard of care.

Vactosertib + Chemoradiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify 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 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

You may not qualify 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 or fluorouracil, oxaliplatin, or vactosertib.
• Subjects with contraindication to radiation therapy.
• Subjects with contraindication to carboplatin and paclitaxel or FOLFOX chemotherapy 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 as following (refer to APPENDIX III). 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).

Sponsors & Collaborators

• Sakti Chakrabarti: lead

Study Sites (1)

University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

vactosertib; Carboplatin

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Sakti Chakrabarti, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sakti Chakrabarti, MD

CONTACT

216-983-3227; Sakti.Chakrabarti@uhhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: September 21, 2023
• Study Start: September 30, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Compiled and analyzed patient data will be published upon study completion. Publisher may request Protocol and Statistical Analysis Plan

Locations

US (1)