14 Participants Needed

Cryotherapy for Esophageal Cancer

SR
AD
BP
Overseen ByBhaumik Patel, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

Background: In published studies, complete response (CR) to chemoradiation occurs in only 25-30% of patients with locally advanced esophageal cancer. Liquid nitrogen spray cryotherapy (LNSC) is postulated to stimulate an anti-tumor immune response. In a preliminary study, the investigators documented CR rate of 56% with a single session of LNSC administered prior to chemoradiation. Before proceeding with larger trials to corroborate these findings, the maximally tolerated dose (MTD) of neoadjuvant LNSC must be determined. The aims of this study are: (1) To determine safety and MTD of LNSC during neoadjuvant chemoradiation in locally advanced esophageal cancer. (2) To assess whether LNSC results in immunogenic cell death. (3) To assess changes in tumor micro-environment with LNSC. Methods: Eligible adult patients with locally advanced esophageal cancer will receive LNSC at the following dose frequencies: Patient 1, 2, and 3: 2 sessions of LNSC prior to chemoradiation (chemoXRT); Patients 4, 5, and 6: 2 sessions LNSC prior to chemoXRT, then 1 session during week 4 of chemoXRT; Patients 7, 8, and 9: 2 sessions LNSC prior to chemoXRT, then 1 session during week 2 and 1 session during week 4 of chemoXRT. If no dose limiting toxicity (DLT) occurs, the investigators will enroll an additional 3 patients to confirm MTD. The investigators will contact patients at 48-hours and 1-week post-procedure to evaluate for adverse events (AEs) and DLTs, and assess for improvements in dysphagia and quality of life (QOL) using the Mellow-Pinkas and EORTC QLQ-OES18 instruments respectively. The investigators will obtain peripheral blood for ELISA and biopsies from the tumor to assess tumor-infiltrating lymphocytes (TILs) and T cell subtypes before the 1st session of LNSC, before the 2nd session of LNSC, and after chemoradiation is completed. Expected results: (1) Dose limiting toxicity (DLT) does not occur when patients received 2 session of LNSC prior to chemoXRT, and 2 sessions during chemoXRT (2) LNSC results in immunogenic cell death, as assessed by increased levels of HMGB1 in serum, and calreticulin in biopsy specimens (CRT) (3) LNSC is associated with increased T cell infiltration and activation (increased TILs, CD8+, CD3+ T cells, and granzyme B), and decrease in regulatory T cells (CD45R0, FOXP3).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Cryotherapy for Esophageal Cancer?

Research shows that cryotherapy, which involves freezing cancer cells, is effective and safe for treating esophageal cancer, especially in early stages and when combined with other treatments like chemotherapy. Studies have demonstrated longer survival rates and fewer complications compared to traditional chemotherapy alone.12345

Is cryotherapy safe for treating esophageal conditions?

Cryotherapy, including endoscopic cryotherapy using liquid nitrogen, has been shown to be generally safe for treating esophageal conditions like Barrett's esophagus and early-stage esophageal cancer. Common side effects include chest pain, difficulty swallowing, and sore throat, but these are usually short-lived. Serious complications are rare, but can include esophageal strictures and, very rarely, gastric perforation.14678

How is cryotherapy different from other treatments for esophageal cancer?

Cryotherapy is unique because it uses extreme cold to destroy cancer cells in the esophagus, offering a non-surgical option that can be used for both early-stage and advanced esophageal cancer. It involves cycles of freezing and thawing, which cause cell death and can be applied endoscopically, making it less invasive than traditional surgery.1291011

Research Team

TS

Tilak Shah, MD

Principal Investigator

McGuire VA Medical Center

Eligibility Criteria

Adults with locally advanced esophageal cancer, confirmed by specific tests and without distant metastases. They must be able to undergo procedures required for the trial and not have severe coagulopathy, a very poor performance status (ECOG ≥3), or be pregnant.

Inclusion Criteria

I have esophageal cancer without spread to distant parts, confirmed by tests.
My cancer is one of the specified types affecting the esophagus or where the stomach meets the esophagus.
My esophageal cancer is advanced but hasn't spread to distant parts of my body.
See 1 more

Exclusion Criteria

I am under 18 years old.
My cancer is located in the early stages of the esophagus.
I cannot have a tube passed into my stomach through my mouth.
See 4 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cryotherapy

Participants receive 2 sessions of liquid nitrogen spray cryotherapy prior to chemoradiation

4 weeks
2 visits (in-person)

Chemoradiation

Participants undergo concurrent chemoradiation for 5 weeks, with additional cryotherapy sessions depending on the group

5 weeks
Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and quality of life

3 weeks
2 visits (in-person), 1 visit (virtual)

Treatment Details

Interventions

  • Cryotherapy
Trial Overview The study is testing Liquid Nitrogen Spray Cryotherapy (LNSC) given before and during standard chemoradiation therapy. It aims to find the highest dose patients can take without serious side effects and see if LNSC helps the immune system fight cancer better.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Cryotherapy before chemoradiation and duringExperimental Treatment1 Intervention
Patients receive 2 sessions of liquid nitrogen spray cryotherapy prior to chemoradiation and one session during chemoradiation
Group II: Cryotherapy before chemoradiationExperimental Treatment1 Intervention
Patients receive 2 sessions of liquid nitrogen spray cryotherapy prior to chemoradiation

Cryotherapy is already approved in European Union, United States, Canada for the following indications:

🇪🇺
Approved in European Union as Cryotherapy for:
  • Pain relief
  • Inflammation reduction
  • Muscle spasm treatment
  • Rheumatoid arthritis
  • Stress and anxiety relief
🇺🇸
Approved in United States as Cryotherapy for:
  • Pain management
  • Muscle soreness reduction
  • Recovery after exercise
  • Fibromyalgia treatment
  • Skin health improvement
🇨🇦
Approved in Canada as Cryotherapy for:
  • Pain relief
  • Inflammation reduction
  • Muscle spasm treatment
  • Arthritis management
  • Postpartum recovery

Find a Clinic Near You

Who Is Running the Clinical Trial?

Hunter Holmes Mcguire Veteran Affairs Medical Center

Lead Sponsor

Trials
37
Recruited
21,600+

McGuire Research Institute

Collaborator

Trials
10
Recruited
380+

References

Updates in Cryotherapy for Barrett's Esophagus. [2021]
Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy. [2021]
Percutaneous comprehensive cryoablation for metastatic esophageal cancer after failure of radical surgery. [2018]
Endoscopic cryotherapy: Indications, techniques, and outcomes involving the gastrointestinal tract. [2022]
Long-Term Survival in Stage IV Esophageal Adenocarcinoma with Chemoradiation and Serial Endoscopic Cryoablation. [2020]
Safety, tolerability, and efficacy of endoscopic low-pressure liquid nitrogen spray cryotherapy in the esophagus. [2021]
Cryotherapy for Barrett's esophagus: Who, how, and why? [2013]
Cryotherapy for Barrett's Esophagus. [2018]
Cryotherapy in the management of premalignant and malignant conditions of the esophagus. [2019]
10.United Statespubmed.ncbi.nlm.nih.gov
Cryotherapy in the management of esophageal dysplasia and malignancy. [2017]
Freezing of the esophagus: histological changes and immunological response. [2009]