Volatile Anaesthesia and Perioperative Outcomes Related to Cancer: the VAPOR-C Trial

VAPOR-C is a randomised study of the impact of IV versus inhaled anaesthesia (propofol versus sevoflurane) and lidocaine versus no lidocaine on duration of disease free survival inpatients with either colorectal or non small cell lung cancer.

Study Overview

• Status: Terminated
• Conditions: Rectal Cancer; Non Small Cell Lung Cancer; Colonic Cancer
• Intervention / Treatment: Drug: Sevoflurane; Drug: Lidocaine IV; Drug: Propofol

Detailed Description

VAPOR-C is a pragmatic, event-driven, randomised controlled trial, with a single blind 2x2 factorial design for sevoflurane/propofol and for intravenous lidocaine infusion / no lidocaine infusion.

This trial is designed to test for superiority in disease free survival (DFS) of propofol (total intravenous anaesthesia -TIVA) over sevoflurane (inhalational volatile anaesthesia) and intravenous lidocaine over no lidocaine in patients undergoing surgery for colorectal or non small cell lung cancer (NSCLC). The combination of two cancer types will help address the need to demonstrate the effects of anaesthetic technique across cancers to inform generalisable anaesthesia guidelines. Both NSCLC and colorectal cancer are important for this study due to high incidence rate, many longer-term survivors, and importantly the high risk of local or distant recurrence despite complete surgical resection. In addition, the study will collect additional data in a nested cohort related to the exploratory objectives.

The study aims to recruit 3,500 patients in Australia, New Zealand, Canada, United States and Europe.

• Study Type: Interventional
• Enrollment (Actual): 254
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • Mackay, Queensland, Australia, 4740
      • Mackay Base Hospital
    • Redcliffe, Queensland, Australia, 4020
      • Redcliffe Hospital
    • Rockhampton, Queensland, Australia, 4700
      • Rockhampton Hospital
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Ballarat Central, Victoria, Australia, 3350
      • Ballarat Base Hospital
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Epping, Victoria, Australia, 3076
      • Northern Hospital
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital, Melbourne
    • Footscray, Victoria, Australia, 3011
      • Western Health Footscray Hospital
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
    • Shepparton, Victoria, Australia, 3630
      • Goulburn Valley Health
    • Wangaratta, Victoria, Australia, 3677
      • Northeast Health, Wangaratta
• New Zealand
  • Auckland, New Zealand, 0620
    • North Shore Hospital
  • Auckland, New Zealand, 2023
    • Auckland City Hospital
• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients aged 18 years or older at screening
2. Has provided written informed consent for the trial
3. Patient with American Joint committee on Cancer (AJCC) 8th edition Stage I-III colorectal cancer or Stage I-IIIa NSCLC, as confirmed by histological or cytological diagnosis. In cases where a histological diagnosis is not possible, suspected diagnosis through imaging techniques is acceptable.
4. Patient has an American Society of Anaesthesiologists (ASA) score of 1 to 3
5. Scheduled to receive elective, surgical resection with curative intent
6. Surgery expected to last ≥2 hours and expected to require ≥2 nights hospital stay
7. Able to comply with protocol requirements and follow-up procedures

Exclusion Criteria:

1. Confirmed or suspected allergy to propofol, sevoflurane or intravenous lidocaine
2. Patient with significant liver disease (with elevated International Normalised Ratio (INR) or bilirubin and/or low albumin; i.e. Childs-Pugh Score >Class A;
3. Patient at personal or familial risk of malignant hyperthermia or porphyria
4. Patient with a history of other malignancies within the past 5 years. However, patients with malignancies managed with curative therapy and considered to be at low risk of recurrence such as treated skin basal cell carcinoma, squamous cell carcinoma, malignant melanoma ≤1.0mm without ulceration, localised thyroid cancer, cervical carcinoma in situ or prior malignancies with high likelihood of cure (e.g. low grade prostate and breast cancer) may be included in the study
5. Patient has distant metastases
6. Patient with an actual body weight less than 45kg
7. Patients taking the following drugs that are moderate-strong inhibitors of the CYP1A2 and CYP3A4 metabolic pathways within 72 hours prior to surgery: Antibiotics - 'mycin' class: Clarithromycin, Telithromycin, Azithromycin, Erythromycin Antibiotics - 'floxacin' class Ciprofloxacin (exception: can be used preoperatively within a bowel prep regime), Norfloxacin, Levofloxacin, Sparfloxacin Antibiotics - other: Chloramphenicol, Isoniazid Antifungals: Fluconazole, Itraconazole, Ketoconazole, Posaconazole, Voriconazole Antiretrovirals: Atazanavir; Darunavir; Indinavir; Lopinavir; Nelfinavir; Ombitasvir, Paritaprevir, Ritonavir and Saquinavir. Antidepressants/ADHD: Fluvoxamine, Enoxacine. Calcium-channel blockers: Diltiazem, Verapamil Monoclonal Antibodies: Ceritinib, Idelalisib, Lonafarnib, Tucatinib. Other strong cytochrome P450 3A4 inhibitors: Cimetidine, Cobicistat; grapefruit juice, Mifepristone, Nefazodone.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Sevoflurane + intravenous lidocaine	Drug: Sevoflurane; Inhaled anaesthetic used for maintenance of anaesthesia, dosed as per standard practice; Drug: Lidocaine IV; 1.5mg/kg loading dose over 20 minutes, followed by an infusion of 2mg/kg/hr up to 4 hours and 1.5mg/kg/hour thereafter. Bolus and maintenance dosages of lidocaine will be per actual body weight and capped at a maximum of 100 kg.
Active Comparator: B; Sevoflurane	Drug: Sevoflurane; Inhaled anaesthetic used for maintenance of anaesthesia, dosed as per standard practice
Active Comparator: C; Propofol TIVA + intravenous lidocaine	Drug: Lidocaine IV; 1.5mg/kg loading dose over 20 minutes, followed by an infusion of 2mg/kg/hr up to 4 hours and 1.5mg/kg/hour thereafter. Bolus and maintenance dosages of lidocaine will be per actual body weight and capped at a maximum of 100 kg.; Drug: Propofol; Intravenous anaesthetic used for induction and maintenance of anaesthesia
Active Comparator: D; Propofol TIVA	Drug: Propofol; Intravenous anaesthetic used for induction and maintenance of anaesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of disease free survival (DFS) with propofol-TIVA versus sevoflurane	The study will collect endpoint data for each participant on time of disease progression. This will be used to compare disease free survival across arms.	Until 3 years from participant index surgery date
Comparison of disease free survival (DFS) with lidocaine compared with no lidocaine	The study will collect endpoint data for each participant on time of disease progression. This will be used to compare disease free survival across arms.	Until 3 years from participant index surgery date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of overall survival (OS) with propofol-TIVA versus sevoflurane	The study will collect endpoint data for each participant on survival status. This will be used to compare overall survival across arms.	Until 3 years from participant index surgery date
Days alive and at home with propofol-TIVA versus sevoflurane	Data will be collected at thirty days post surgery regarding date of discharge from hospital and survival status. This is then used to calculate number of days alive and at home (i.e. out of hospital) and compare across arms.	30 days post surgery
Overall survival with intravenous lidocaine versus no lidocaine	The study will collect endpoint data for each participant on survival status. This will be used to compare overall survival across arms.	Until 3 years from participant index surgery date
Days alive and at home with intravenous lidocaine versus no lidocaine	Data will be collected at thirty days post surgery regarding date of discharge from hospital and survival status. This is then used to calculate number of days alive and at home (i.e. out of hospital) and compare across arms.	30 days post surgery
Comparison of post-operative complications with propofol-TIVA versus sevoflurane	Short term postoperative morbidity assessed by the Post Operative Morbidity Scale (POMS) with Clavien-Dindo severity grading. POMS is an 18-item tool that addresses nine domains of morbidity relevant to the post-surgical patient . The severity in each POMS domain will then be graded according to the Clavien-Dindo Classification on the basis of treatment applied to correct each respective complication , and captures complications within 5 grades.	5 days post surgery or at discharge if earlier
Comparison of post-operative complications with intravenous lidocaine versus no lidocaine	Short term postoperative morbidity assessed by the Post Operative Morbidity Scale (POMS) with Clavien-Dindo severity grading. POMS is an 18-item tool that addresses nine domains of morbidity relevant to the post-surgical patient . The severity in each POMS domain will then be graded according to the Clavien-Dindo Classification on the basis of treatment applied to correct each respective complication , and captures complications within 5 grades.	5 days post surgery or at discharge if earlier
Comparison of chronic post surgical pain with propofol-TIVA versus sevoflurane	Pain measured using the Brief Pain Inventory Short Form. Patient reported pain on a scale of 0 to 10 where 0 is no pain and 10 is worst pain. Pain measured using the Neuropathic Pain Questionnaire. Patient reported neuropathic pain on a scale of 0 to 100 where 0 is no pain and 100 is worst pain.	At 90 days and 12 months post surgery
Comparison of chronic post surgical pain with intravenous lidocaine versus no lidocaine	Pain measured using the Brief Pain Inventory Short Form. Patient reported pain on a scale of 0 to 10 where 0 is no pain and 10 is worst pain. Pain measured using the Neuropathic Pain Questionnaire. Patient reported neuropathic pain on a scale of 0 to 100 where 0 is no pain and 100 is worst pain.	At 90 days and 12 months post surgery
Safety profile of propofol-TIVA versus sevoflurane	Toxicities measured using CTCAE V 5 .0	during surgery until discharge from Post Anaesthetic Care Unit (PACU) or within the first 4 hours of ICU admission
Safety Profile intravenous lidocaine versus no lidocaine	Toxicities measured using CTCAE V 5 .0	during surgery until discharge from Post Anaesthetic Care Unit (PACU) or within the first 4 hours of ICU admission
Concomitant medication use with propofol-TIVA versus sevoflurane	From 2 weeks prior to surgery up to Day 5 post-surgery administration of relevant medications will be recorded	5 days post anaesthesia
Concomitant medications use with intravenous lidocaine versus no lidocaine	From 2 weeks prior to surgery up to Day 5 post-surgery administration of relevant medications will be recorded	5 days post anaesthesia
Health utility with propofol-TIVA versus sevoflurane	The EQ-5D-5L is a standardised instrument for use as a measure of health outcome and is applicable to a wide range of health conditions and treatments. This five item scale covers the following dimensions (5D): mobility, self-care, usual activities, pain/discomfort and anxiety/depression, with each dimension having five levels (5L). The use of the EQ-5D-5L will enable utility valuations to be estimated for health states experienced.	At 30 days, 90 days and every 12 months post surgery up to 3 years
Health utility with intravenous lidocaine versus no lidocaine	The EQ-5D-5L is a standardised instrument for use as a measure of health outcome and is applicable to a wide range of health conditions and treatments. This five item scale covers the following dimensions (5D): mobility, self-care, usual activities, pain/discomfort and anxiety/depression, with each dimension having five levels (5L). The use of the EQ-5D-5L will enable utility valuations to be estimated for health states experienced	At 30 days, 90 days and every 12 months post surgery up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of return to intended oncological treatment (RIOT) with propofol-TIVA versus sevoflurane	Data will be collected post surgery regarding post treatment adjuvant therapy given according to plan. A comparison will be made between number of participants receiving post surgery oncological treatment as planned and the number of patients deviating from the plan in each arm of the study.	At 90 days and 12 months post surgery
Comparison of return to intended oncological treatment (RIOT) with intravenous lidocaine versus no lidocaine	Data will be collected post surgery regarding post treatment adjuvant therapy given according to plan. A comparison will be made between number of participants receiving post surgery oncological treatment as planned and the number of patients deviating from the plan in each arm of the study.	At 90 days and 12 months post surgery
Correlative blood studies	Inflammatory markers - Neutrophil to lymphocyte ratio (NLR), Platelet to lymphocyte ratio (PLR), C-reactive protein (CRP) Circulating tumour deoxyribonucleic acid (ctDNA), DNA/RNA, Circulating tumour cells (CTCs), immune profile using flow cytometry and plasma for cytokines These are exploratory transnational research outcomes levels of these biomarkers will be measured over the course of the study and analysed for correlation the study outcomes.	Preop, Day 1, 3 and 5 (if still an inpatient) and at recurrence
Correlative breath biopsy studies	To characterise the effect of anaesthetic agents on perioperative inflammatory changes will measure Targeted Volatile Organic Compounds of the eicosanoid pathway by sampling patients breath (breath biopsy) to monitor inflammatory changes within the pulmonary compartment.	Preop, Day 1, 3 and 5 (if still an inpatient) and at recurrence
MINS Substudy	At sites who agree to participate: Blood Specimens and 12-Lead ECG - 12 Lead ECGS will be done and blood specimens collected to measure Troponin levels at baseline, Day 1 and Day 2 post op. Assessment of the predefined diagnostic criteria for MINS and perioperative myocardial infarction on Day 5 or Discharge if earlier Assessment of predefined diagnostic criteria for MINS and myocardial infarction at 30 days post op.	Day 0 to day 30

Collaborators and Investigators

• Sponsor: Peter MacCallum Cancer Centre, Australia
• Collaborators: National Health and Medical Research Council, Australia; Australian and New Zealand College of Anaesthetists; Victorian Comprehensive Cancer Centre
• Investigators: Principal Investigator: Bernhard Riedel, MB.ChB, Peter MacCallum Cancer Centre, Australia

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2020
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): February 28, 2025

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Colonic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Anesthetics, Inhalation; Sevoflurane; Lidocaine; Propofol
• Other Study ID Numbers: 18/044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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