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Liquid Nitrogen Spray Cryotherapy prior to Neoadjuvant Therapy for the Treatment of Locally Advanced Esophageal Adenocarcinoma
Trial Status: active
This phase II trial tests liquid nitrogen spray cryotherapy prior to chemotherapy consisting of fluorouracil, leucovorin, oxaliplatin, and docetaxel with or without durvalumab, given before surgery (neoadjuvant) for the treatment of esophageal adenocarcinoma that has spread to nearby tissue or lymph nodes (locally advanced). Cryotherapy kills tumor cells by freezing them using liquid nitrogen spray. Fluorouracil is in a class of medications called antimetabolites. It works by stopping or slowing the growth of cancer cells. Leucovorin is used to lessen the toxic effects of substances that block the action of folic acid, such as fluorouracil. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell’s DNA and may kill cancer cells. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving liquid nitrogen spray cryotherapy prior to neoadjuvant chemotherapy may work well for the treatment of locally advanced esophageal adenocarcinoma.
Inclusion Criteria
Adult patients 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 positron emission tomography (PET)-computed tomography (CT)
Exclusion Criteria
Inability to pass the orogastric decompression tube into the stomach
Coagulopathy (International normalization ratio [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 determined to be too high to hold anti-platelets (other than aspirin) or anticoagulants prior to the procedure
Microsatellite unstable on biopsy specimen
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07222657.
I. To compare clinical and pathologic complete response (CR) rates with liquid nitrogen spray cryotherapy (LNSC) + neoadjuvant systemic therapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] +/- durvalumab) compared to neoadjuvant systemic therapy alone in locally advanced esophageal adenocarcinoma (EAC).
SECONDARY OBJECTIVES:
I. To compare rates of minimal residual disease (MRD) after neoadjuvant therapy in patients who received LNSC + neoadjuvant systemic therapy versus (vs.) neoadjuvant systemic therapy alone.
II. To compare overall survival (OS) at 1-year with LNSC + neoadjuvant systemic therapy (FLOT +/- durvalumab) compared to neoadjuvant systemic therapy alone in locally advanced EAC.
III. To compare systemic immune response with LNSC + systemic neoadjuvant therapy vs. systemic neoadjuvant therapy alone.
IV. Assess improvement in dysphagia, quality of life (QoL) (European Organization for Research and Treatment of Cancer [EORTC]-18 instrument), and LNSC-related adverse events with spray cryotherapy.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo standard of care endoscopic ultrasound (EUS) and receive cryotherapy with liquid nitrogen spray at time of staging and 1-2 weeks later in the absence of disease progression or unacceptable toxicity. Patients may begin chemotherapy 48 hours later. Patients receive fluorouracil, leucovorin, oxaliplatin, and docetaxel with or without durvalumab for 6-8 cycles in the absence of disease progression or unacceptable toxicity. Patients then proceed to esophagectomy surgery at the discretion of their care team. Patients undergo diagnostic imaging on study and blood sample collection throughout the study.
ARM II: Patients undergo standard of care EUS at time of staging. Patients receive fluorouracil, leucovorin, oxaliplatin, and docetaxel with or without durvalumab for 6-8 cycles in the absence of disease progression or unacceptable toxicity. Patients then proceed to esophagectomy surgery at the discretion of their care team. Patients undergo diagnostic imaging on study and blood sample collection throughout the study.
