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

Non Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04316013
• Other study ID #: 18/044
• Status: Recruiting
• Phase: Phase 3
• Start date: July 31, 2020
• Est. completion date: June 2028

Study information

• Verified date: March 2023
• Source: Peter MacCallum Cancer Centre, Australia
• Contact: Bernhard Riedel, MB.ChB
• Phone: +61385597663
• Email: bernhard.riedel[@]petermac.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3500
• Est. completion date: June 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colonic Cancer
• Colonic Neoplasms
• Non Small Cell Lung Cancer
• Rectal Cancer

Intervention

Drug:
• Sevoflurane
Inhaled anaesthetic used for maintenance of anaesthesia, dosed as per standard practice
• Propofol
Intravenous anaesthetic used for induction and maintenance of anaesthesia
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Ballarat Base Hospital	Ballarat Central	Victoria
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Northern Hospital	Epping	Victoria
Australia	St Vincent's Hospital, Melbourne	Fitzroy	Victoria
Australia	Western Health Footscray Hospital	Footscray	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Mackay Base Hospital	Mackay	Queensland
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	RedCliffe Hospital	Redcliffe	Queensland
Australia	Rockhampton Hospital	Rockhampton	Queensland
Australia	Goulburn Valley Health	Shepparton	Victoria
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Northeast Health, Wangaratta	Wangaratta	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
New Zealand	Auckland City Hospital	Auckland
New Zealand	North Shore Hospital	Auckland
United States	Cleveland Clinic	Cleveland	Ohio
United States	The University of Texas MD Anderson Cancer Centre	Houston	Texas
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
Peter MacCallum Cancer Centre, Australia	Australian and New Zealand College of Anaesthetists, National Health and Medical Research Council, Australia, Victorian Comprehensive Cancer Centre

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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