Liquid Nitrogen Spray Cryotherapy Prior to Neoadjuvant Systemic Therapy in Esophageal Adenocarcinoma

NCT07222657 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: CASE14225
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is for people who have locally advanced esophageal adenocarcinoma and are expected to receive chemotherapy. The purpose of this study is to compare the effectiveness of Liquid Nitrogen Spray Cryotherapy (LNSC) in addition to chemotherapy versus chemotherapy alone in the treatment of esophageal adenocarcinoma. LNSC is an FDA approved device that works by using liquid nitrogen to rapidly cool cancerous tissue causing cell damage. Participants in this study will be randomly assigned to either the "LNSC group" or the "No-LNSC group." Participants in the "LNSC group" will undergo 2 sessions of LNSC through an upper endoscopy. Participants in the "No-LNSC group," may undergo an endoscopy if needed for symptoms such as difficulty swallowing. Participation in the research will last about 4 months.

Conditions

Esophageal Adenocarcinoma; Esophageal Cancer

Keywords

Liquid Nitrogen Spray Cryotherapy; LNSC

Outcome Measures

Primary Outcomes (1)

• Complete response (CR) rates

  CR is defined as the absence of tumor on re-staging scans and explant or mucosal biopsies (if applicable).

  At treatment discontinuation, up to 12 weeks

Secondary Outcomes (6)

• Change in minimal residual disease (MRD)

  Week 4 of chemotherapy, 2-4 weeks post-chemotherapy (up to 16 weeks)

• Overall survival (OS)

  1 year

• Change in systemic immune response

  Baseline, 4 weeks post-chemotherapy, up to 16 weeks

• Change in dysphagia

  Baseline, up to 2 weeks

• Change in quality of life (QoL)

  Baseline, up to 2 weeks

Study Arms (2)

Liquid Nitrogen Spray Cryotherapy (LNSC) + Standard of care chemotherapy

EXPERIMENTAL

Participants will receive a standard of care chemotherapy, neoadjuvant FLOT +/- durvalumab WITH LNSC.

Other: Standard of care chemotherapy; Procedure: LNSC

Standard of care chemotherapy

OTHER

Participants will receive a standard of care chemotherapy, neoadjuvant FLOT +/- durvalumab WITHOUT LNSC.

Other: Standard of care chemotherapy

Interventions

Standard of care chemotherapy OTHER

Participants will receive neoadjuvant therapy per FLOT protocol +/- Durvalumab for up to 6 cycles. Each cycle is two weeks. The FLOT protocol is a standard of care protocol involving chemotherapy before and after esophagectomy with fluorouracil, leucovorin, oxaliplatin, and docetaxel. Durvalumab is administered intravenously (IV) and dosed at 1500 milligrams (mg). It is given on Day 1 of each cycle.

Liquid Nitrogen Spray Cryotherapy (LNSC) + Standard of care chemotherapy; Standard of care chemotherapy

LNSC PROCEDURE

LNSC will be administered via endoscopy. LNSC will be performed with liquid nitrogen (\<5 psi) at 25 watts using a cryotherapy catheter passed through the working channel of the endoscope. Up to three cycles of 20 to 40 seconds of cryotherapy will be administered and each directed at the bulkiest aspect of the tumor. During each cycle, a surface area of approximately 2 to 3 cm2 is targeted, and up to three sites are targeted during each session. Participants will receive two sessions of LNSC. The first will be upon entry into the study. The second will be 1-2 weeks after the first session.

Liquid Nitrogen Spray Cryotherapy (LNSC) + Standard of care chemotherapy

Eligibility Criteria

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

You may qualify if:

• Adults with locally advanced EAC who are expected to receive FLOT +/-Durvalumab will be eligible to participate.
• Locally advanced esophageal cancer is defined as TNM stages T1N+M0 or T2-T4aNanyM0, as defined by endoscopic ultrasound (EUS) and PET-CT.

You may not qualify if:

• Inability to pass the orogastric decompression tube into the stomach
• Coagulopathy (INR \> 2 or platelet count \< 50,000 per cubic millimeter)
• Inability to provide informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status \> 2
• Risk of thrombosis is determined to be too high to hold anti-platelets (other than aspirin) or anticoagulants prior to the procedure.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• Salgi Foundation: collaborator

Study Sites (1)

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Related Publications (5)

• van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.

  PMID: 22646630 BACKGROUND

• Kachaamy T, Sharma N, Shah T, Mohapatra S, Pollard K, Zelt C, Jewett E, Garcia R, Munsey R, Gupta S, Rojas-DeLeon M, Gupta D, Kaul V, Pannala R, Vashi P. A prospective multicenter study to evaluate the impact of cryotherapy on dysphagia and quality of life in patients with inoperable esophageal cancer. Endoscopy. 2023 Oct;55(10):889-897. doi: 10.1055/a-2105-2177. Epub 2023 Jun 2.

  PMID: 37268010 BACKGROUND

• Shah T, Kushnir V, Mutha P, Majhail M, Patel B, Schutzer M, Mogahanaki D, Smallfield G, Patel M, Zfass A. Neoadjuvant cryotherapy improves dysphagia and may impact remission rates in advanced esophageal cancer. Endosc Int Open. 2019 Nov;7(11):E1522-E1527. doi: 10.1055/a-0957-2798. Epub 2019 Oct 31.

  PMID: 31681831 BACKGROUND

• Shah T, Koblinski J, Boothello R, Haneefa SM, Massey HD, Patel BB. Changes in Local Tumor Immune Microenvironment with Neoadjuvant Cryotherapy and Chemoradiation for Locally Advanced Esophageal Cancer. Foregut. 2024;0(0).

  BACKGROUND

• Shah T, Spataro J, Mutha P et al. Phase 1 dose frequency escalation study of neoadjuvant cryotherapy in locally advanced esophageal cancer. Gastrointestinal Endoscopy, Volume 97, Issue 6, AB1106 - AB1107.

  BACKGROUND

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Tilak Shah, MD

  Case Comprehensive Cancer Center, Cleveland Clinic Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tilak Shah, MD

CONTACT

561-497-8859; shaht3@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2025
• First Posted: October 30, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Within 6 months of study completion
• Access Criteria: Public

Locations

US (1)