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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join 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 cannot join 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.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

Treatments listed in the registry

• 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.
• 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.

Randomized · Parallel · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• questionnaires: Part of the study plan
• endoscopy: Part of the study plan
• surgery: Part of the study plan

Main goals

• Complete response (CR) rates (At treatment discontinuation, up to 12 weeks)

Other goals

• Change in minimal residual disease (MRD)
• Overall survival (OS)
• Change in systemic immune response
• Change in dysphagia
• Change in quality of life (QoL)
• LNSC-related adverse events

Planned enrollment: 40 (estimated).

• Cleveland Clinic Florida, Weston, Florida

Site status as of Oct 30, 2026. Check the live record before contacting a site.

These papers are listed in the registry record. Unless a paper is marked as about this trial, it is background research on the treatment or disease, not results from this study.

• Background research, not results from this trialvan 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.
• Background research, not results from this trialKachaamy 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.
• Background research, not results from this trialShah 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.
• Background research, not results from this trial

  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 research, not results from this trial

  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.

• ClinicalTrials.gov NCT07222657

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Aug 17, 2026. Public record; not medical advice.