Clinical trial NCT04316013: Volatile Anaesthesia and Perioperative Outcomes Related to Cancer: the VAPOR-C Trial
Official title: Volatile Anaesthesia and Perioperative Outcomes Related to Cancer: the VAPOR-C Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Colonic Cancer
Rectal Cancer
Non Small Cell Lung Cancer
Lead sponsor: Peter MacCallum Cancer Centre, Australia
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: Australian and New Zealand College of Anaesthetists
name: Victorian Comprehensive Cancer Centre
First posted: 2020-03-20
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 .
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Comparison of disease free survival (DFS) with propofol-TIVA versus sevoflurane
timeFrame: Until 3 years from participant index surgery date
measure: Comparison of disease free survival (DFS) with lidocaine compared with no lidocaine
timeFrame: Until 3 years from participant index surgery date
Secondary outcomes:
measure: Comparison of overall survival (OS) with propofol-TIVA versus sevoflurane
timeFrame: Until 3 years from participant index surgery date
measure: Days alive and at home with propofol-TIVA versus sevoflurane
timeFrame: 30 days post surgery
measure: Overall survival with intravenous lidocaine versus no lidocaine
timeFrame: Until 3 years from participant index surgery date
measure: Days alive and at home with intravenous lidocaine versus no lidocaine
timeFrame: 30 days post surgery
measure: Comparison of post-operative complications with propofol-TIVA versus sevoflurane
timeFrame: 5 days post surgery or at discharge if earlier
measure: Comparison of post-operative complications with intravenous lidocaine versus no lidocaine
timeFrame: 5 days post surgery or at discharge if earlier
measure: Comparison of chronic post surgical pain with propofol-TIVA versus sevoflurane
timeFrame: At 90 days and 12 months post surgery
measure: Comparison of chronic post surgical pain with intravenous lidocaine versus no lidocaine
timeFrame: At 90 days and 12 months post surgery
measure: Safety profile of propofol-TIVA versus sevoflurane
timeFrame: during surgery until discharge from Post Anaesthetic Care Unit (PACU) or within the first 4 hours of ICU admission
measure: Safety Profile intravenous lidocaine versus no lidocaine
timeFrame: during surgery until discharge from Post Anaesthetic Care Unit (PACU) or within the first 4 hours of ICU admission
measure: Concomitant medication use with propofol-TIVA versus sevoflurane
timeFrame: 5 days post anaesthesia
measure: Concomitant medications use with intravenous lidocaine versus no lidocaine
timeFrame: 5 days post anaesthesia
measure: Health utility with propofol-TIVA versus sevoflurane
timeFrame: At 30 days, 90 days and every 12 months post surgery up to 3 years
measure: Health utility with intravenous lidocaine versus no lidocaine
timeFrame: At 30 days, 90 days and every 12 months post surgery up to 3 years
Other outcomes:
measure: Comparison of return to intended oncological treatment (RIOT) with propofol-TIVA versus sevoflurane
timeFrame: At 90 days and 12 months post surgery
measure: Comparison of return to intended oncological treatment (RIOT) with intravenous lidocaine versus no lidocaine
timeFrame: At 90 days and 12 months post surgery
measure: Correlative blood studies
timeFrame: Preop, Day 1, 3 and 5 (if still an inpatient) and at recurrence
measure: Correlative breath biopsy studies
timeFrame: Preop, Day 1, 3 and 5 (if still an inpatient) and at recurrence
measure: MINS Substudy
timeFrame: Day 0 to day 30
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Centre
state: Texas
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Mackay
country: Australia
facility: Mackay Base Hospital
state: Queensland
city: Redcliffe
country: Australia
facility: RedCliffe Hospital
state: Queensland
city: Rockhampton
country: Australia
facility: Rockhampton Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Ballarat Central
country: Australia
facility: Ballarat Base Hospital
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Epping
country: Australia
facility: Northern Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital, Melbourne
state: Victoria
city: Footscray
country: Australia
facility: Western Health Footscray Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Shepparton
country: Australia
facility: Goulburn Valley Health
state: Victoria
city: Wangaratta
country: Australia
facility: Northeast Health, Wangaratta
state: Victoria
city: Auckland
country: New Zealand
facility: North Shore Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
affiliation: Peter MacCallum Cancer Centre, Australia
name: Bernhard Riedel, MB.ChB
role: PRINCIPAL_INVESTIGATOR
References: