Clinical trial NCT06330038: Anesthesia and Non-small Cell Lung Cancer Recurrence
Official title: Recurrence Free Survival After Curative Resection of Non-small Cell Lung Cancer Between Inhalational Gas Anesthesia and Propofol-based Total IntraVenous Anesthesia: a Multicenter, Randomized, Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Non-small Cell Lung Cancer
Surgery
Anesthesia
Keywords: Anesthesia
Desflurane
Inhalational anesthesia
Isoflurane
Lung neoplasm
Metastasis
Propofol
Recurrence
Sevoflurane
Surgery
Non-small cell lung cancer
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Seoul National University Hospital
name: Asan Medical Center
name: Severance Hospital
name: Seoul St. Mary's Hospital
name: Korea University Guro Hospital
name: DongGuk University
name: Inha University Hospital
name: Konkuk University Medical Center
name: Ewha Womans University
name: Chungnam National University Hospital
name: University of Virginia
name: Memorial Sloan Kettering Cancer Center
name: Yale University
name: Mayo Clinic
name: University of Texas Southwestern Medical Center
name: University Hospitals Coventry and Warwickshire NHS Trust
name: Khon Kaen University
name: King Chulalongkorn Memorial Hospital
name: The Affiliated Hospital of Qingdao University
name: Beijing Hospital
name: All India Institute of Medical Sciences
First posted: 2024-03-26
Enrollment: 5384
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: There has been ongoing debate about the relationship between cancer recurrence and anesthetic management. Therefore, the investigators will test the hypothesis that the recurrence free survival (RFS) after curative resection of NSCLC is higher in patient who received total intravenous anesthesia (TIVA) than volatile anesthetics in this multi-center randomized trials.

Detailed description: Surgery is the primary treatment for non-small cell lung cancer (NSCLC), but microscopic residual disease may be unavoidable. Preclinical studies have shown that volatile anesthetics might suppress host immunity and promote a pro-malignant environment which supports cancer cell proliferation, migration, and angiogenesis, whereas propofol may preserve cell-mediated immunity and inhibits tumor angiogenesis. However, clinical evidence that propofol-based total intravenous anesthesia (TIVA) can reduce tumor recurrence after curative resection remains inconsistent due to retrospective observational nature of previous studies. Therefore, the investigators will test the hypothesis that the recurrence free survival (RFS) after curative resection of NSCLC is higher in patient who received TIVA than volatile anesthetics in this multi-center randomized trials.

This double-blind, randomized trial will enroll patients at 22 international sites, subject to study registration, institutional review board approval, and patient written informed consent. Eligible patients are adult patients undergoing lung resection surgery with curative intent for NSCLC. At each study site, enrolled subjects will be randomly allocated into the TIVA and GAS group with a 1:1 ratio. A centralized, password-protected, and encrypted web-based electronic case report form will be used for randomization and data upload. This pragmatic trial does not standardize any aspect of patient care. However, potential confounders will be balanced between the study arms.

The primary outcome will be recurrence free survival (RFS). Secondary outcomes will be overall survival and complications within postoperative 7 days. Enrollment of 5384 patients will provide 80% power to detect a 3% treatment effect (hazard ratio of 0.83) at alpha 0.05 for RFS at 3 years.

Confirmation of the study hypothesis would demonstrate that a relatively minor and low cost alteration in anesthetic management has the potential to reduce cancer recurrence risk in NSCLC, an ultimately fatal complication. Rejection of the hypothesis would end the ongoing debate about the relationship between cancer recurrence and anesthetic management.

Eligibility criteria: Inclusion Criteria:

* American Society of Anesthesiologists physical status (ASA) Ⅰ-Ⅲ
* The Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Lung resection surgery (segmentectomy, lobectomy, bilobectomy, pneumonectomy; video-assisted, robot-assisted, or open) with curative intent for NSCLC (clinical Tumor, Node, Metastasis (TNM) stage Ⅰ- ⅢA).

Exclusion Criteria:

* Distant metastasis or malignant tumor in other organs that according to the attending surgeon is not in long-term remission
* Severe neurologic conditions
* Severe hepatic disease (Child-Pugh classification C)
* Renal failure requiring renal replacement therapy
* History of anesthesia and/or surgery within 1 yr
* Previous surgery due to lung cancer (except diagnostic biopsies)
* Contraindications to any study medication (history of allergy, hypersensitivity reaction, or any other contraindication)
* Planned joint extrapulmonary procedure
* Surgery under cardiopulmonary bypass or extracorporeal membrane oxygenation
* Postoperative sedation
* Pregnancy, or lactation
* Patient refusal.

Primary outcomes:
measure: Recurrence free survival
timeFrame: Within 3 year after curative resection for NSCLC
Secondary outcomes:
measure: Overall survival
timeFrame: Within 3 year after curative resection for NSCLC
measure: Postoperative complications
timeFrame: within 7 days post-surgery or at discharge if earlier
Other outcomes:
Locations:
Study officials:
affiliation: Department of Anesthesiology and Pain Medicine, Samsung Medical Center
name: Hyun Joo Ahn
role: PRINCIPAL_INVESTIGATOR
References: