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Female Breast CancerNCT03005860

Effect of TIVA Propofol vs Sevoflurane Anaesthetic on Serum Biomarkers and on PBMCs in Breast Cancer Surgery

A study testing 2,6-Diisopropylphenol, Fluoromethyl hexafluoroisopropyl ether and Fentanyl Citrate in people with Female Breast Cancer, run by Tata Memorial Centre at 1 site in India.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Surgery, perioperative stress, anaesthetics and analgesics may modulate the immunosurveillance mechanisms and overwhelm host defences that normally maintain a balance between immunity \& carcinogenesis. This may lead to escape of cancer cells and tilt the scales toward a more protumorigenic microenvironment. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Female Breast Cancer
What is being tested?
2,6-Diisopropylphenol, Fluoromethyl hexafluoroisopropyl ether and Fentanyl Citrate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteIndia
Study dates
1 Jan 2017to Dec 2020
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Women with histopathologically (biopsy/FNAC) proven breast carcinoma with Resectable disease (T 1-4, N 0-1, M 0) [Stage I-III].
  • Willing for upfront modified radical mastectomy.
  • ASA Physical Status 1-2

Who cannot join

  • use of morphine or on steroid therapy upto 3 months before surgery;
  • history of substance abuse or cognitive dysfunction;
  • endocrine disorders- diabetes, hypothyroid;
  • history of HIV, Hep-B or Hep-C infections;
  • Contraindication to analgesics or anaesthetic drugs;
  • Pregnant \& lactating women

Trial locations and contacts

1 site in 1 country.

India1 site

  • Tata Memorial Centre

    Mumbai, Maharashtra, 400012

Other trials in India

About this study

Official title: A Prospective, Randomized, Controlled Trial to Compare the Effect of TIVA Propofol vs Sevoflurane Anaesthetic on Serumserum Biomarkers and on PBMCs in Patients Undergoing Breast Cancer Resection Surgery

Surgery, perioperative stress, anaesthetics and analgesics may modulate the immunosurveillance mechanisms and overwhelm host defences that normally maintain a balance between immunity \& carcinogenesis. This may lead to escape of cancer cells and tilt the scales toward a more protumorigenic microenvironment. Volatile agents, in particular, have been shown to exhibit profound immunosuppressive effects. In comparison, propofol has a favorable profile and inhibits cancer cell activity. Determining "cancer-protective" role of TIVA with propofol presents an exciting window of opportunity that has potential to improve outcomes in cancer patients undergoing resection surgery

Read the detailed description

For the current study, consenting patients planned for upfront surgery, will be randomly allocated to 2 groups- 20 patients each group: Propofol TCI-based Total Intravenous Anesthesia group (Propofol group) and Sevoflurane group (Sevoflurane group), according to computer generated randomization number.

Patients will be monitored routinely with ECG, non invasive blood pressure, and a pulse- oximetery (SPO2), every 5 min. An intravenous access will be established with 20- 22 G cannula. A perioperative antibiotic prophylaxis will be given to all patients. None of the patients will receive any premedication.

After preoxygenation with 100% O2 for 3 min: group specific separate interventions will be performed.

Patient will be ventilated with TV of 6-8ml/kg,respiratory rate will be adjusted to maintain end-tidal CO2 value between 40 - 45 mmHg. Crystalloids will be used for hydration (4-6 ml/kg/h), and intraoperative volume deficits will be replaced by additional administration of a solution according to clinical needs. For TIVA group, the depth of anaesthesia will be monitored using Bispectral Index, with target BIS value between 40 and 60. For Sevoflurane group, the depth of anaesthesia will be monitored using MAC, with target MAC value between 0.8 and 1. Half hour before conclusion of surgery, all patients will receive 0.1mg/kg of ondansetron as prophylaxis for PONV. At the end of surgery, muscle relaxation will be reversed by glycopyrrolate (10mcg/kg) and neostigmine (50mcg/kg).

Patients in both groups will receive intra-venous non-steroidal anti-inflammatory drug 1-1.5mg/kg diclofenac + Paracetamol 1gm just before conclusion of surgery for postoperative analgesia. Postoperative pain \& PONV will be managed as per institutional protocols.

ASSAY Peripheral blood (5ml) will be collected from patients in EDTA vaccutainer and (5ml) in another vaccutainer containing clot activator. The sample will be collected at following time points.

  1. before anaesthesia (Tpre)
  2. after removal of tumor intraoperative (Ti)
  3. 2 h after surgery (T2h) , and
  4. (T24h) 24 hours after surgery

Estimation of serum cytokines : by sandwich ELISA and by cytokine bead array (CBA) method.

Expression of various lymphocyte subsets (CD3+ T cells, CD4+ helper T cells, CD8+ cytotoxic T cells, γδT cells, NK cells and B cells) by flow cytometry

Being tested
2,6-Diisopropylphenol, Fluoromethyl hexafluoroisopropyl ether, Fentanyl Citrate, Atracurium Besylate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 2,6-DiisopropylphenolDrug

    Also called Fresofol 1%, Fresenius Kabi

    In Propofol group, anesthesia will be induced with Propofol TCI using Schneider model to achieve a target site concentration of 4 - 6 mcg/ml. Propofol TCI to achieve BIS (Bispectral Index) between 40-60.

  • Fluoromethyl hexafluoroisopropyl etherDrug

    Also called Sevoflurane

    In Sevoflurane group, anesthesia will be induced with 5 - 7mg/kg thiopental, maintenance with O2 with air 50:50%, sevoflurane 2-2.5 %, Further fentanyl, in increments of 1 mcg/kg - and atracurium 0.15 mg/kg, will be given as indicated by the clinical signs and hemodynamic changes.

  • Fentanyl CitrateDrug

    Also called Verfen 100mcg/2ml, Verve

    Inj. fentanyl 2 mcg/kg will be used as an adjunct during anaesthetic induction.

  • Atracurium BesylateDrug

    Also called Atrapure 25mg/2.5ml, Samarth Life Sciences Pvt. Ltd.

    Inj. atracurium 0.5 mg/kg for will be administered for facilitating LMA placement

Study groups in NCT03005860
Study groupRoleWhat they receive
Fluoromethyl hexafluoroisopropyl etherActive comparatorIn Sevoflurane group, anaesthesia will be induced with Thiopental 5 - 7mg/kg, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with sevoflurane 2-2.2 % to maintain a target MAC value between 0.8 \& 1.0.
Receives: Drug: Fluoromethyl hexafluoroisopropyl ether; Drug: Fentanyl Citrate; Drug: Atracurium Besylate
2,6 diisopropylphenolExperimentalIn Propofol group, anesthesia will be will be induced with Propofol TCI [target controlled infusion pump - Injectomat® TIVA Agilia (Fresenius Kabi)] using Schneider model to achieve target site concentration of 4-6mcg/ml, fentanyl citrate 2mcg/kg and atracurium besylate 0.5mg /kg to facilitate LMA placement. Anaesthesia will be maintained with TCI propofol at 3 - 6 mcg/ml as effect site concentration to maintain BIS 40-60.
Receives: Drug: 2,6-Diisopropylphenol; Drug: Fentanyl Citrate; Drug: Atracurium Besylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in baseline levels versus 24 hour postoperative levels (Tpre vs T24h ) of serum HIF-1a and VEGF-C in both groups.

    The primary objective of this study is to compare the potential effects of inhalation anesthetic (Sevoflurane) with intravenous anesthetic agent (Propofol) on preoperative levels versus 24hour postoperative levels (Tpre vs T24h ) of serum Hypoxia Inducible Factor-1 alpha (HIF-1a) and Vascular Endothelial Growth Factor -C (VEGF-C) in patients with breast cancer undergoing resection surgery.

    Measured: Baseline levels versus 24 hour postoperative levels (Tpre vs T24h )

Secondary outcomes (3)

  1. Change in levels of serum biomarkers HIF-1a & VEGF-C in patients with breast cancer undergoing resection surgery at other time points - intraoperative, at 2hr postoperative. Ti, T2h in both groups.

    Change in levels of serum biomarkers HIF-1a \& VEGF-C in patients with breast cancer undergoing resection surgery at other time points - intraoperative, at 2hr postoperative. Ti, T2h in both groups

    Measured: after removal of tumor intraoperative (Ti) and 24 hours after surgery (T24h)

  2. Change in levels of serum biomarkers TGF-β, IL-17 IFN-g, TNF-a, IL-6 and MMP-2 at the four time points in both groups.

    Transforming Growth Factor -beta (TGF-β), Interleukin - 17 (IL-17), Inferferon - gamma (IFN-g), Tumor Necrosis Factor - alpha (TNF-a), Interleukin - 6 (IL-6), Matrix Metalloproteinase - 2 (MMP-2)

    Measured: preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.

  3. Measure expression of various lymphocyte subsets (CD3+ T cells, CD4+ helper T cells, CD8+ cytotoxic T cells, γδT cells, NK cells and B cells peripheral blood lymphocytes at four time points

    Measure expression of various lymphocyte

    Measured: preoperative, intraoperative, at 2hr postoperative and at 24hr postoperative.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Dec 2016 (estimated)
  2. Study start1 Jan 2017 (estimated)
  3. Primary completionOct 2020 (estimated)
  4. Study completionDec 2020 (estimated)

Why it stopped: Funding could not be arranged, so the study was prematurely terminated

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03005860
Sponsor's protocol ID
PN 219
Status last verified
Mar 2020
First submitted
20 Dec 2016
Last updated
21 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Dikshit RP, Yeole BB, Nagrani R, Dhillon P, Badwe R, Bray F. Increase in breast cancer incidence among older women in Mumbai: 30-year trends and predictions to 2025. Cancer Epidemiol. 2012 Aug;36(4):e215-20. doi: 10.1016/j.canep.2012.03.009. Epub 2012 Apr 20.

    PubMed 22521561

  • Weigelt B, Peterse JL, van 't Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005 Aug;5(8):591-602. doi: 10.1038/nrc1670.

    PubMed 16056258

  • Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004 Aug;21(2):137-48. doi: 10.1016/j.immuni.2004.07.017.

    PubMed 15308095

  • 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.

    PubMed 21935924

  • Tsuchiya Y, Sawada S, Yoshioka I, Ohashi Y, Matsuo M, Harimaya Y, Tsukada K, Saiki I. Increased surgical stress promotes tumor metastasis. Surgery. 2003 May;133(5):547-55. doi: 10.1067/msy.2003.141.

    PubMed 12773983

  • Boomsma MF, Garssen B, Slot E, Berbee M, Berkhof J, Meezenbroek Ede J, Slieker W, Visser A, Meijer S, Beelen RH. Breast cancer surgery-induced immunomodulation. J Surg Oncol. 2010 Nov 1;102(6):640-8. doi: 10.1002/jso.21662.

    PubMed 20677220

  • Camara O, Kavallaris A, Noschel H, Rengsberger M, Jorke C, Pachmann K. Seeding of epithelial cells into circulation during surgery for breast cancer: the fate of malignant and benign mobilized cells. World J Surg Oncol. 2006 Sep 26;4:67. doi: 10.1186/1477-7819-4-67.

    PubMed 17002789

  • 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.

    PubMed 24803747

  • 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.

    PubMed 23242747

  • Melamed R, Bar-Yosef S, Shakhar G, Shakhar K, Ben-Eliyahu S. Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures. Anesth Analg. 2003 Nov;97(5):1331-1339. doi: 10.1213/01.ANE.0000082995.44040.07.

    PubMed 14570648

  • Mammoto T, Mukai M, Mammoto A, Yamanaka Y, Hayashi Y, Mashimo T, Kishi Y, Nakamura H. Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett. 2002 Oct 28;184(2):165-70. doi: 10.1016/s0304-3835(02)00210-0.

    PubMed 12127688

  • Looney M, Doran P, Buggy DJ. Effect of anesthetic technique on serum vascular endothelial growth factor C and transforming growth factor beta in women undergoing anesthesia and surgery for breast cancer. Anesthesiology. 2010 Nov;113(5):1118-25. doi: 10.1097/ALN.0b013e3181f79a69.

    PubMed 20930611

  • Xu YJ, Chen WK, Zhu Y, Wang SL, Miao CH. Effect of thoracic epidural anaesthesia on serum vascular endothelial growth factor C and cytokines in patients undergoing anaesthesia and surgery for colon cancer. Br J Anaesth. 2014 Jul;113 Suppl 1:i49-55. doi: 10.1093/bja/aeu148. Epub 2014 Jun 25.

    PubMed 24966150

  • 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.

    PubMed 26556730

  • Gisterek I, Matkowski R, Kozlak J, Dus D, Lacko A, Szelachowska J, Kornafel J. Evaluation of prognostic value of VEGF-C and VEGF-D in breast cancer--10 years follow-up analysis. Anticancer Res. 2007 Jul-Aug;27(4C):2797-802.

    PubMed 17695450

Questions about this trial

What is this clinical trial studying?

A study testing 2,6-Diisopropylphenol, Fluoromethyl hexafluoroisopropyl ether and Fentanyl Citrate in people with Female Breast Cancer, run by Tata Memorial Centre at 1 site in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in baseline levels versus 24 hour postoperative levels (Tpre vs T24h ) of serum HIF-1a and VEGF-C in both groups. (time frame: Baseline levels versus 24 hour postoperative levels (Tpre vs T24h )). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03005860, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2023.

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