Cryotherapy for Esophageal Cancer

Recruiting in Palo Alto (17 mi)

Overseen byTilak Shah, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center

Stay on Your Current Meds

No Placebo Group

Approved in 3 Jurisdictions

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).

Research Team

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

Treatment Details

Interventions

Cryotherapy (Other)

Trial OverviewThe 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: