NCT04475705

Brief Summary

Background: Retrospective studies and meta-analyses have shown a reduction in 5-year survival following inhalational based compared to propofol based total intravenous (TIVA) anaesthesia for cancer surgery. To date there have been no prospective trials published which evaluate the effect of anaesthetic technique on circulating tumour cells (CTC), oxidative stress, and recurrence rate following cancer surgery. Children with cancer often require surgery for tumour excision as well as for other diagnostic and therapeutic procedures. To date there has been no prospective randomized controlled trial evaluating the optimal anaesthetic technique for surgery on children with cancer. Aim: This is a pilot study in paediatric patients who require surgery for tumour excision. The aim is to investigate the effect of sevoflurane inhalational versus propofol intravenous anaesthesia on expression of hypoxia-inducible factor 1 (HIF-1), circulating tumour cells, DNA damage and biomarkers of immunity and inflammation in patients before and after tumour surgery. The patients will be followed up for up to 5 years for tumour recurrence after surgery. Method: This will be a single-blinded randomized controlled trial. One hundred children undergoing tumour excision surgery at the Hong Kong Children's Hospital will be recruited and randomized to receive TIVA or inhalational anaesthesia. Baseline, intraoperative and postoperative blood will be taken for tests of immunity and inflammatory markers, DNA damage and circulating tumour cells. Patients would be followed up to 3 years for tumour recurrence and survival.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for phase_4

Timeline
26mo left

Started Jan 2021

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress71%
Jan 2021Jul 2028

First Submitted

Initial submission to the registry

July 7, 2020

Completed
10 days until next milestone

First Posted

Study publicly available on registry

July 17, 2020

Completed
6 months until next milestone

Study Start

First participant enrolled

January 11, 2021

Completed
7.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2028

Last Updated

March 16, 2022

Status Verified

March 1, 2022

Enrollment Period

7.5 years

First QC Date

July 7, 2020

Last Update Submit

March 14, 2022

Conditions

Solid TumorCarcinomaMalignancyCancer

Keywords

propofolsevofluranecancer surgerycirculating tumor cellspaediatric

Outcome Measures

Primary Outcomes (1)

  • difference in Hypoxia Inducible Factor-1 gene expression

    pg/mL

    intraoperative to postoperative 24 hours

Secondary Outcomes (10)

  • difference in levels of Interleukin-6

    intraoperative to postoperative 24 hours

  • difference in levels of Tumor Necrosis Factor-alpha

    intraoperative to postoperative 24 hours

  • difference in levels of high sensitivity C reaction protein

    intraoperative to postoperative 24 hours

  • difference in levels of DNA damage (Comet Assay)

    intraoperative to postoperative 24 hours

  • difference in levels of Glutathione Peroxidase

    intraoperative to postoperative 24 hours

  • +5 more secondary outcomes

Study Arms (2)

Sevoflurane group

ACTIVE COMPARATOR

patients in this group will receive inhalation anaesthesia with sevoflurane at Minimal Alveolar Concentration 0.7-1.3 as the main anaesthetic to achieve Bispectral Index 40-60. Other anaesthetic management will be standardised.

Drug: sevoflurane

propofol group

ACTIVE COMPARATOR

patients in this group will receive intravenous propofol using Target Controlled Infusion 'Paedfusor' model 2-5 as the main anaesthetic to achieve Bispectral Index 40-60. Other anaesthetic management will be standardised.

Drug: propofol

Interventions

propofolDRUG

intravenous propofol using Target Controlled Infusion 'Paedfusor' model 2-5 as the main anaesthetic to achieve Bispectral Index 40-60

Also known as: Diprivan
propofol group
sevofluraneDRUG

sevoflurane at Minimal Alveolar Concentration 0.7-1.3 as the main anaesthetic to achieve Bispectral Index 40-60.

Also known as: ultane, sevorane
Sevoflurane group

Eligibility Criteria

Age6 Months - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • patients coming for elective primary solid tumor resection for curative intent in Hong Kong Children's Hospital
  • AND patients \> 5kg
  • AND patients within age limit

You may not qualify if:

  • Autoimmune / Chronic inflammatory diseases e.g. Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) etc.
  • Current Steroid therapy
  • Surgery for tumour removal in the past year
  • Allergy to Propofol
  • intraoperative use of nitrous oxide
  • Patient susceptible to Malignant Hyperthermia
  • Patients / parents / legal guardians showing preference in anaesthetic techniques during recruitment process

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hong Kong Children's Hospital

Hong Kong, Hong Kong

RECRUITING

Related Publications (9)

  • Divatia JV, Ambulkar R. Anesthesia and cancer recurrence: What is the evidence? J Anaesthesiol Clin Pharmacol. 2014 Apr;30(2):147-50. doi: 10.4103/0970-9185.129990. No abstract available.

    PMID: 24803747BACKGROUND

  • Heaney A, Buggy DJ. Can anaesthetic and analgesic techniques affect cancer recurrence or metastasis? Br J Anaesth. 2012 Dec;109 Suppl 1:i17-i28. doi: 10.1093/bja/aes421.

    PMID: 23242747BACKGROUND

  • Vinay DS, Ryan EP, Pawelec G, Talib WH, Stagg J, Elkord E, Lichtor T, Decker WK, Whelan RL, Kumara HMCS, Signori E, Honoki K, Georgakilas AG, Amin A, Helferich WG, Boosani CS, Guha G, Ciriolo MR, Chen S, Mohammed SI, Azmi AS, Keith WN, Bilsland A, Bhakta D, Halicka D, Fujii H, Aquilano K, Ashraf SS, Nowsheen S, Yang X, Choi BK, Kwon BS. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin Cancer Biol. 2015 Dec;35 Suppl:S185-S198. doi: 10.1016/j.semcancer.2015.03.004. Epub 2015 Mar 25.

    PMID: 25818339BACKGROUND

  • Demicheli R, Retsky MW, Hrushesky WJ, Baum M, Gukas ID. The effects of surgery on tumor growth: a century of investigations. Ann Oncol. 2008 Nov;19(11):1821-8. doi: 10.1093/annonc/mdn386. Epub 2008 Jun 10.

    PMID: 18550576BACKGROUND

  • Tavare AN, Perry NJ, Benzonana LL, Takata M, Ma D. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. Int J Cancer. 2012 Mar 15;130(6):1237-50. doi: 10.1002/ijc.26448. Epub 2011 Nov 9.

    PMID: 21935924BACKGROUND

  • Benzonana LL, Perry NJ, Watts HR, Yang B, Perry IA, Coombes C, Takata M, Ma D. Isoflurane, a commonly used volatile anesthetic, enhances renal cancer growth and malignant potential via the hypoxia-inducible factor cellular signaling pathway in vitro. Anesthesiology. 2013 Sep;119(3):593-605. doi: 10.1097/ALN.0b013e31829e47fd.

    PMID: 23774231BACKGROUND

  • Kushida A, Inada T, Shingu K. Enhancement of antitumor immunity after propofol treatment in mice. Immunopharmacol Immunotoxicol. 2007;29(3-4):477-86. doi: 10.1080/08923970701675085.

    PMID: 18075859BACKGROUND

  • Huitink JM, Heimerikxs M, Nieuwland M, Loer SA, Brugman W, Velds A, Sie D, Kerkhoven RM. Volatile anesthetics modulate gene expression in breast and brain tumor cells. Anesth Analg. 2010 Dec;111(6):1411-5. doi: 10.1213/ANE.0b013e3181fa3533. Epub 2010 Oct 1.

    PMID: 20889943BACKGROUND

  • Wigmore TJ, Mohammed K, Jhanji S. Long-term Survival for Patients Undergoing Volatile versus IV Anesthesia for Cancer Surgery: A Retrospective Analysis. Anesthesiology. 2016 Jan;124(1):69-79. doi: 10.1097/ALN.0000000000000936.

    PMID: 26556730BACKGROUND

MeSH Terms

Conditions

CarcinomaNeoplasmsNeoplastic Cells, Circulating

Interventions

PropofolSevoflurane

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasm MetastasisNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsMethyl EthersEthersHydrocarbons, FluorinatedHydrocarbons, Halogenated

Study Officials

  • Sau Man Lee, MBBS

    Hong Kong Children's Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Sau Man Lee, MBBS

CONTACT

+85257413327lsm335@gmail.com

Vivian Yuen, MBBS

CONTACT

+85235133752yuenmyv@ha.org.hk

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: single blind controlled trial
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 7, 2020

First Posted

July 17, 2020

Study Start

January 11, 2021

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

July 1, 2028

Last Updated

March 16, 2022

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will not share

Locations

HK(1)