Vactosertib for Esophageal Cancer

Overseen By Sakti Chakrabarti, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jennifer Eva Selfridge, MD

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Active malignancy, Uncontrolled illness, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new pill called vactosertib to determine its effectiveness in treating esophageal cancer. The pill targets a protein that may kill cancer cells and is administered before patients begin their standard chemotherapy and radiation treatment. Participants take vactosertib for two weeks before the usual treatment and again for four weeks after, to assess its impact on their cancer. Individuals with esophageal adenocarcinoma who are preparing for chemotherapy and radiation might be suitable candidates, especially if they haven't undergone previous cancer treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires stopping certain medications that interact with vactosertib, specifically those that are strong CYP3A4 inhibitors or inducers, and some other drugs with narrow therapeutic indices. A washout period (time without taking certain medications) of 5 half-lives is recommended before starting the trial.

Is there any evidence suggesting that vactosertib is likely to be safe for humans?

Research has shown that vactosertib, an oral medication, was safe and well tolerated in earlier studies. One study found that the most common side effect was fatigue. Importantly, the highest safe dose was not reached, suggesting high tolerability. In another study, vactosertib was tested alongside other cancer treatments and revealed no unexpected safety issues. These findings suggest that vactosertib is generally safe for humans. However, as with any treatment, side effects can vary from person to person. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for esophageal cancer?

Unlike the standard treatments for esophageal cancer, such as chemotherapy and radiation, Vactosertib offers a novel approach by targeting a specific pathway involved in cancer progression. Researchers are excited because Vactosertib is designed to inhibit the TGF-beta pathway, which plays a crucial role in tumor growth and metastasis. This targeted action has the potential to enhance the effectiveness of traditional chemoradiotherapy, offering a new hope for improving patient outcomes with potentially fewer side effects.

What evidence suggests that vactosertib might be an effective treatment for esophageal cancer?

Research has shown that vactosertib targets a protein called TGF-beta, which aids cancer cell growth and spread. By blocking this protein, vactosertib may halt or slow the growth of esophageal cancer cells. Early lab studies suggest that vactosertib can kill these cancer cells, especially when combined with standard treatments like chemoradiation. In this trial, participants will receive vactosertib alongside standard chemoradiotherapy. Although more human studies are necessary, early evidence appears promising for those with localized esophageal adenocarcinoma. ^{2 5 6 7 8}

Who Is on the Research Team?

Sakti Chakrabarti, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with localized esophageal adenocarcinoma who haven't had prior treatments for this cancer. They must be fit enough for surgery, have normal liver and kidney function tests, acceptable blood counts, and an ECOG performance status of ≤2 (able to carry out light activity).

Inclusion Criteria

I have not had chemo, immunotherapy, or radiation for this cancer (except for treatments targeting Barrett's metaplasia).

I can take care of myself but might not be able to do heavy physical work.

My bilirubin levels are below 2 mg/dl, or below 3 mg/dl if I have Gilbert syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment with Vactosertib

Participants take vactosertib orally, 200 mg twice daily for five days a week for 2 weeks

2 weeks

1 visit (in-person) for PET CT scan and endoscopy with biopsy

Chemoradiotherapy

Participants undergo standard of care chemoradiotherapy

6 weeks

Post-Chemoradiotherapy Treatment with Vactosertib

Participants take vactosertib for 4 weeks after standard of care chemoradiotherapy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vactosertib

Trial Overview The study tests if a pill called vactosertib can improve outcomes when taken before and after standard chemoradiation therapy in esophageal cancer patients. The effects are monitored using PET CT scans and biopsies.

How Is the Trial Designed?

Group I: Vactosertib + Chemoradiotherapy Experimental Treatment 3 Interventions

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

Who Is Running the Clinical Trial?

Jennifer Eva Selfridge, MD

Lead Sponsor

Trials

2

Recruited

40+

Sakti Chakrabarti

Lead Sponsor

Trials

1

Recruited

30+

Jennifer Eva Selfridge

Lead Sponsor

Trials

2

Recruited

40+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06044311

Oral TGF-beta Receptor I Inhibitor Vactosertib in SOC ... This interventional clinical trial aims to find ways of improving treatments for individuals with esophageal cancer. Laboratory-based studies show that ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11756299/

Is it time to retire preoperative radiation for localized ... Esophageal cancer outcomes are poor, with the relative 5-year survival rate for all stages of 21.6%. For microsatellite stable tumors ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06044311/oral-tgf-beta-receptor-i-inhibitor-vactosertib-in-soc-chemoradiotherapy-for-esophageal-adenocarcinoma

Oral TGF-beta Receptor I Inhibitor Vactosertib in SOC ... This interventional clinical trial aims to find ways of improving treatments for individuals with esophageal cancer.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02160106

First in Human Dose Escalation Study of Vactosertib (TEW- ... The study will investigate the safety, tolerability, and pharmacokinetics of TEW-7197, and will define the maximum tolerated dose (MTD) of TEW-7197 using a 3 + ...

5. meetings.asco.org meetings.asco.org/abstracts-presentations/159220/abstracts

Abstract Vactosertib (TEW-7197) is a potent, highly selective, oral inhibitor of TGFBR1. The safety, anti-tumor effect of vactosertib and its association with TBRS ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02160106?term=TEW-7197&viewType=Table&rank=4

First in Human Dose Escalation Study of Vactosertib (TEW ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

7. medpacto.com medpacto.com/uploadata/publication/12/12_2022-10-18

Safety and Preliminary Clinical Activity of Vactosertib, a ... vactosertib with pembrolizumab in metastatic colorectal cancer (mCRC) or diffuse gastric cancer (GC) and gastro-esophageal junction cancer. (GEJC). • Here we ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11337916/

Oral transforming growth factor‐beta receptor 1 inhibitor ... Oral TGF-βR1 inhibitor Vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity.