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

Peter MacCallum Cancer Centre, Australia

Status and phase: Terminated; Phase 3

Conditions: Colonic Cancer; Non Small Cell Lung Cancer; Rectal Cancer

Treatments: Drug: Sevoflurane; Drug: Lidocaine IV; Drug: Propofol

Study type: Interventional

Funder types: Other

Identifiers

NCT04316013

18/044

Details and patient eligibility

About

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.

Full 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.

Enrollment: 254 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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254 participants in 4 patient groups

A

Active Comparator group

Description:

Sevoflurane + intravenous lidocaine

Treatment:

Drug: Lidocaine IV

Drug: Sevoflurane

B

Active Comparator group

Description:

Sevoflurane

Treatment:

Drug: Sevoflurane

C

Active Comparator group

Description:

Propofol TIVA + intravenous lidocaine

Treatment:

Drug: Propofol

Drug: Lidocaine IV

D

Active Comparator group

Description:

Propofol TIVA

Treatment:

Drug: Propofol