Cryotherapy for Locally Advanced Esophageal Cancer

NCT04248582 | Active Not Recruiting Phase 1 DMC FDA Device

• 1 other identifier: SHAH 008
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Esophageal Cancer

Keywords

Cryotherapy; Cryoablation

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  We hypothesize that 1) DLT will not occur when patients receive 2 sessions of LNSC prior to chemoradiation, and 2 sessions during chemoradiation (i.e. - a total of 4 sessions) for locally advanced esophageal cancer

  12 weeks

Study Arms (2)

Cryotherapy before chemoradiation

EXPERIMENTAL

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

Device: Cryotherapy

Cryotherapy before chemoradiation and during

EXPERIMENTAL

Patients receive 2 sessions of liquid nitrogen spray cryotherapy prior to chemoradiation and one session during chemoradiation

Device: Cryotherapy

Interventions

Cryotherapy DEVICE

LNSC will be performed with low-pressure liquid nitrogen (\<5 psi) at 25 watts using a cryotherapy catheter passed through the working channel of the endoscope.We will plan to administer LNSC as follows: up to three cycles of 20 to 40 seconds each directed at the bulkiest aspect of the tumor. During each cycle, a surface area of approximately 2 to 3 cm2 is targeted. Up to three sites are treated during each session. Tissue thawing is verified between cycles by waiting at least 60 seconds before re-treatment, and by observing a return to baseline color of the tissue and complete disappearance of ice crystals after reperfusion. After the procedure is completed, patients will be monitored in the recovery unit for at least 30 minutes. Patients will be discharged after monitoring if they meet the endoscopy unit's standard discharge criteria.

Also known as: Cryoablation

Cryotherapy before chemoradiation; Cryotherapy before chemoradiation and during

Eligibility Criteria

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

You may qualify if:

• Adult patients with locally advanced esophageal cancer will be eligible to participate in the study. Eligible patients must have a histologically proven diagnosis of esophageal adenocarcinoma, esophageal squamous cell carcinoma, adenosquamous carcinoma, or gastro-esophageal junctional adenocarcinoma. Locally advanced esophageal cancer will be defined as absence of distant metastases on positron emission tomography-computed tomography (PET-CT) and a TNM stage of IIA to IIIC, as defined by endoscopic ultrasound and PET-CT

You may not qualify if:

• Pediatric patients (age less than 18 years)
• Superficial esophageal cancer
• Inability to pass the orogastric decompression tube into the stomach
• Coagulopathy (INR \> 2 or platelet count \< 50,000/cubic millimeter).
• Inability to provide informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status ≥3
• Pregnancy

Sponsors & Collaborators

• McGuire Research Institute: collaborator
• Hunter Holmes Mcguire Veteran Affairs Medical Center: lead

Study Sites (1)

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Cryotherapy; Cryosurgery

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Tilak Shah, MD

  McGuire VA Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 28, 2020
• First Posted: January 30, 2020
• Study Start: February 11, 2020
• Primary Completion: March 8, 2023
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)