Cryodevitalization for the Treatment of Early Stage Lung Cancer, CRYSTAL Trial

PRIMARY OBJECTIVE:

I. To identify the maximum tolerated dose (MTD) for cryodevitalization cycle duration.

OUTLINE: This is a dose-escalation study.

Patients undergo 3 freeze-thaw cycles of cryodevitalization over 30 seconds or 3, 5, or 7 minutes each during standard of care robotic bronchoscopy with biopsy on study. Patients then undergo standard of care surgical resection on study. Patients also undergo a chest radiography (x-ray) on study as well as computed tomography (CT) and tissue sample collection throughout the study.

After completion of study treatment, patients are followed up at 3 and 7 days and are then followed as clinically required per standard of care for 24 months.

Inclusion criteria

• Patients with a single pulmonary nodule with a size less than or equal to three centimeters (average long and short axis) confirmed as malignant intraprocedurally (rapid on-site evaluation with pathology assessment showing lung cancer or oligometastatic disease) without evidence of mediastinal involvement who require nodule biopsy prior to proceeding with surgical resection
• Nodules must be located in the outer 2/3 of the periphery of the lung, greater than 10 mm from the pleura and from large blood vessels or mediastinal structures to avoid injury to other visceral organs
• Patients deemed to have a surgical resection treatment option based on preoperative staging computed tomographic (CT), postoperative predicted forced expiratory volume in 1 second (FEV1) > 40% and evaluation of medical comorbidities after discussion at multidisciplinary tumor board
• Age > 18 years old

Exclusion criteria

• Target nodule is within the International Association for the Study of Lung Cancer (IASLC) "central zone" (including bronchial tree, major vessels, heart, esophagus, spinal cord and phrenic & laryngeal nerves), or are < 10 mm from the pleura
• Patients with an expected survival less than 6 months
• Patients with endobronchial lesions, concerning for malignancy, visualized during the initial bronchoscopic evaluation of the airways
• Patients with medically uncorrectable coagulopathy: abnormal platelet count < 100 × 10^9/L or an international normalized ratio > 1.5
• Patients with known pulmonary hypertension (PASP [pulmonary artery systolic pressure] > 50mmHg)
• Patients who are currently prescribed anticoagulants, clopidogrel, or other platelet aggregation inhibitors
• Patients with medical comorbidities deemed high-risk for surgical resection
• Pregnant women
• Inability to provide informed consent