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

August 17, 2026 updated by: Fabien Maldonado, Vanderbilt-Ingram Cancer Center

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

Active, not recruiting

Conditions

Intervention / Treatment

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 (Actual)

13

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Vanderbilt University/Ingram Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: At time of surgery
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
Time Frame: At time of surgery
Proportion of procedures that can be safely completed with full dose delivered
At time of surgery
Incidence of adverse events
Time Frame: Up to 7 days post-cryosurgery
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
Time Frame: At time of surgical resection
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
Time Frame: From day 8 post-cryosurgery to surgical resection
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

This is where you will find people and organizations involved with this study.

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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 27, 2024

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

August 31, 2027

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)

August 18, 2026

Last Update Submitted That Met QC Criteria

August 17, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe