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

NCT04316013 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: 18/044
• Study Type: interventional
• Target: 254
• Locations: 3 countries
• Sites: 27

Brief Summary

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.

Conditions

Colonic Cancer; Rectal Cancer; Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (14)

• Comparison of overall survival (OS) with propofol-TIVA versus sevoflurane

  Until 3 years from participant index surgery date

• Days alive and at home with propofol-TIVA versus sevoflurane

  30 days post surgery

• Overall survival with intravenous lidocaine versus no lidocaine

  Until 3 years from participant index surgery date

• Days alive and at home with intravenous lidocaine versus no lidocaine

  30 days post surgery

• Comparison of post-operative complications with propofol-TIVA versus sevoflurane

  5 days post surgery or at discharge if earlier

Other Outcomes (5)

• Comparison of return to intended oncological treatment (RIOT) with propofol-TIVA versus sevoflurane

  At 90 days and 12 months post surgery

• Comparison of return to intended oncological treatment (RIOT) with intravenous lidocaine versus no lidocaine

  At 90 days and 12 months post surgery

• Correlative blood studies

  Preop, Day 1, 3 and 5 (if still an inpatient) and at recurrence

Study Arms (4)

A

ACTIVE COMPARATOR

Sevoflurane + intravenous lidocaine

Drug: Sevoflurane; Drug: Lidocaine IV

B

ACTIVE COMPARATOR

Sevoflurane

Drug: Sevoflurane

C

ACTIVE COMPARATOR

Propofol TIVA + intravenous lidocaine

Drug: Propofol; Drug: Lidocaine IV

D

ACTIVE COMPARATOR

Propofol TIVA

Drug: Propofol

Interventions

Sevoflurane DRUG

Inhaled anaesthetic used for maintenance of anaesthesia, dosed as per standard practice

A; B

Propofol DRUG

Intravenous anaesthetic used for induction and maintenance of anaesthesia

C; D

Lidocaine IV DRUG

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.

A; C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 years or older at screening
• Has provided written informed consent for the trial
• 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.
• Patient has an American Society of Anaesthesiologists (ASA) score of 1 to 3
• Scheduled to receive elective, surgical resection with curative intent
• Surgery expected to last ≥2 hours and expected to require ≥2 nights hospital stay
• Able to comply with protocol requirements and follow-up procedures

You may not qualify if:

• Confirmed or suspected allergy to propofol, sevoflurane or intravenous lidocaine
• Patient with significant liver disease (with elevated International Normalised Ratio (INR) or bilirubin and/or low albumin; i.e. Childs-Pugh Score \>Class A;
• Patient at personal or familial risk of malignant hyperthermia or porphyria
• 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
• Patient has distant metastases
• Patient with an actual body weight less than 45kg
• 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.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• National Health and Medical Research Council, Australia: collaborator
• Australian and New Zealand College of Anaesthetists: collaborator
• Victorian Comprehensive Cancer Centre: collaborator

Study Sites (27)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

The University of Texas MD Anderson Cancer Centre

Houston, Texas, 77030, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Mackay Base Hospital

Mackay, Queensland, 4740, Australia

Location

RedCliffe Hospital

Redcliffe, Queensland, 4020, Australia

Location

Rockhampton Hospital

Rockhampton, Queensland, 4700, Australia

Location

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Ballarat Base Hospital

Ballarat Central, Victoria, 3350, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Northern Hospital

Epping, Victoria, 3076, Australia

Location

St Vincent's Hospital, Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Western Health Footscray Hospital

Footscray, Victoria, 3011, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Goulburn Valley Health

Shepparton, Victoria, 3630, Australia

Location

Northeast Health, Wangaratta

Wangaratta, Victoria, 3677, Australia

Location

North Shore Hospital

Auckland, 0620, New Zealand

Location

Auckland City Hospital

Auckland, 2023, New Zealand

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Sevoflurane; Propofol

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Bernhard Riedel, MB.ChB

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The propofol-TIVA/sevoflurane element of each arm will have a single blind (patient blinded), as the administering anesthesiologist cannot be blinded to allocation. The lidocaine infusion or no lidocaine infusion element of each ARM will be blinded to the patient . The anaesthetic team and research team caring for the patient will not be blinded to the lidocaine infusion/no lidocaine infusion element of the randomisation ARM
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an event-driven, international multicentre, randomised controlled trial with a 2x2 factorial design. Patients with stage I-III colorectal cancer or stage I-IIIa NSCLC are eligible and will be randomised in the ratio of 1:1:1:1 using permuted block randomisation with stratification by cancer type (Colon, Rectal or NSCLC), and by site to receive either 1) sevoflurane maintenance anaesthesia and lidocaine infusion or 2) sevoflurane maintenance anaesthesia; or 3), propofol maintenance anaesthesia and lidocaine infusion or 4), propofol maintenance anaesthesia .

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: March 20, 2020
• Study Start: July 31, 2020
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (22); US (3); NZ (2)