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

The CRYSTAL Study: Cryodevitalization Study for the Treatment of Early-Stage Lung Cancer

This clinical trial studies side effects and best treatment time of cryodevitalization in treating patients with early stage (stage I or stage II) lung cancer. Cryodevitalization is a type of cryosurgery that uses a flexible probe (cryoprobe) to kill tumor cells by freezing them. It is delivered at the time of standard diagnostic robotic bronchoscopy. Using cryodevitalization may be safe, tolerable and/or effective in treating patients with early stage lung cancer.

Study Overview

• Status: Recruiting
• Conditions: Stage I Lung Cancer; Stage II Lung Cancer
• Intervention / Treatment: Procedure: Chest Radiography; Other: Electronic Health Record Review; Procedure: Resection; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Procedure: Cryosurgery; Procedure: Robotic Bronchoscopy; Procedure: Bronchoscopy with Biopsy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vanderbilt-Ingram Services for Timely Access; Phone Number: 800-811-8480; Email: cip@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Vanderbilt University/Ingram Cancer Center
      • Principal Investigator: Fabien Maldonado, MD
      • Contact: Vanderbilt-Ingram Service for Timely Access; Phone Number: 800-811-8480; Email: cip@vumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; 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 x-ray on study as well as CT and tissue sample collection throughout the study.

Procedure: Chest Radiography; Undergo chest x-ray; Other: Electronic Health Record Review; Ancillary studies; Procedure: Resection; Undergo standard of care surgical resection; Procedure: Computed Tomography; Undergo Computed Tomography; Procedure: Biospecimen Collection; Undergo tissue sample collection; Procedure: Cryosurgery; Undergo cryodevitalization; Procedure: Robotic Bronchoscopy; Undergo standard of care robotic bronchoscopy with biopsy; Procedure: Bronchoscopy with Biopsy; Undergo standard of care robotic bronchoscopy with biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose for cryodevitalization cycle duration	Will implement a modified Toxicity Probability Interval design. Each dose will be modeled using a Beta-Binomial model with the prior distribution, Beta (1,1). For each dose level, a 95% credible interval for the toxicity probability will be computed.	At time of surgery
Feasibility of bronchoscopically delivered cryodevitalization	Proportion of procedures that can be safely completed with full dose delivered	At time of surgery
Incidence of adverse events	Will be modeled using a Beta-Binomial model with the prior distribution, Beta (1,1). For each dose level, a 95% credible interval for the toxicity probability will be computed.	Up to 7 days post-cryosurgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic response	Pathologic response will be assessed comparing the confirmed devitalization zone determined by intraprocedural cone-beam computed tomography imaging (percent tumor treated by cryodevitalization) and remaining tumor viability by histopathologic examination of resected specimens.	At time of surgical resection
Incidence of adverse events	Will be modeled using a Beta-Binomial model with the prior distribution, Beta (1,1). For each dose level, a 95% credible interval for the toxicity probability will be computed.	From day 8 post-cryosurgery to surgical resection

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI); Swim Across America
• Investigators: Principal Investigator: Fabien Maldonado, MD, Vanderbilt University/Ingram Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2024
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: September 5, 2024
• First Submitted That Met QC Criteria: September 9, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Cytological Techniques; Cytodiagnosis; Physical Phenomena; Diagnostic Techniques, Surgical; Endoscopy; Diagnostic Techniques, Respiratory System; Electromagnetic Phenomena; Magnetic Phenomena; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Thoracic Surgical Procedures; Ablation Techniques; Pulmonary Surgical Procedures; Biopsy; X-Rays; Cryosurgery; Bronchoscopy
• Other Study ID Numbers: VICC-VCTHO24099; P30CA068485 (U.S. NIH Grant/Contract); NCI-2024-07299 (Registry Identifier: NCI, Clinical Trials Reporting Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No