Regional Anesthesia and Breast Cancer Recurrence

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Outcomes Research Consortium
Sponsor:
Information provided by (Responsible Party):
Daniel I. Sessler, M.D., Outcomes Research Consortium
ClinicalTrials.gov Identifier:
NCT00418457
First received: January 3, 2007
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

In this multi-center trial, Stage 1-3 patients having mastectomies or isolated lumpectomy with axillary node dissection will be randomly assigned to thoracic epidural or paravertebral anesthesia/analgesia, or to general anesthesia and morphine analgesia. Participants will be followed for up to 10 years to determine the rate of cancer recurrence or metastasis.


Condition Intervention Phase
Breast Neoplasms
Drug: Sevoflurane
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Regional Anesthesia and Breast Cancer Recurrence

Resource links provided by NLM:


Further study details as provided by Outcomes Research Consortium:

Primary Outcome Measures:
  • Cancer recurrence rate [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • post-surgical pain [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]
    Chronic post-surgical pain is reduced by paravertebral or thoracic epidural analgesia.


Estimated Enrollment: 1100
Study Start Date: January 2007
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
General anesthesia followed by opioid administration
Drug: Sevoflurane
Sevoflurane
Other Name: General anesthesia
Active Comparator: 2
Regional anesthesia and analgesia (either epidural or paravertebral), combined with deep sedation or general anesthesia
Drug: Sevoflurane
Regional anesthesia and analgesia (either epidural or paravertebral), combined with deep sedation or general anesthesia

Detailed Description:

Surgery is the primary and most effective treatment of breast cancer, but residual disease in the form of scattered micrometastases and tumor cells are usually unavoidable. Whether minimal residual disease results in clinical metastases is a function of host defense and tumor survival and growth. At least three perioperative factors shift the balance toward progression of minimal residual disease:

  1. Surgery per se depresses cell-mediated immunity, reduces concentrations of tumor-related anti-angiogenic factors (e.g., angiostatin and endostatin), increases concentrations of pro-angiogenic factors such as VEGF, and releases growth factors that promote local and distant growth of malignant tissue.
  2. Anesthesia impairs numerous immune functions, including those of neutrophils, macrophages, dendritic cells, T-cell, and natural killer cells.
  3. Opioid analgesics inhibit both cellular and humoral immune function in humans, increase angiogenesis, and promote breast tumor growth in rodents.

However, regional analgesia attenuates or prevents each of these adverse effects by largely preventing the neuroendocrine surgical stress response, eliminating or reducing the need for general anesthesia, and minimizing opioid requirement. Animal studies indicate that regional anesthesia and optimum postoperative analgesia independently reduce the metastatic burden in animals inoculated with breast adenocarcinoma cells following surgery. Preliminary data in cancer patients are also consistent: paravertebral analgesia for breast cancer surgery reduced risk of recurrence or metastasis approximately four-fold (95% CI of estimated hazard ratio is 0.71 - 0.06) during a 2.5 to 4-year follow-up period compared to opioid analgesia. The investigators will thus test the hypothesis that recurrence after breast cancer surgery is lower with regional anesthesia/analgesia than with general anesthesia and opioid analgesia.

In this multi-center trial, Stage 1-3 patients having mastectomies will be randomly assigned to thoracic epidural or paravertebral anesthesia/analgesia, or to general anesthesia and opioid analgesia. Enrolling 1,100 patients over 5 years will provide an 85% power for detecting a 30% treatment effect at an alpha of 0.05 with a total of four potential stopping points. Confirming our hypothesis will indicate that a minor modification to anesthetic management, one that can be implemented with little risk or cost, will reduce the risk of cancer recurrence — a complication that is often ultimately lethal.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Primary breast cancer without known extension beyond the breast and axillary nodes (i.e. believed to be Tumor Stage 1-3, Nodes 0-2)
  • Scheduled for unilateral or bilateral mastectomy with or without implant (isolated "lumpectomy" will not qualify)
  • Isolated "lumpectomy" with axillary node dissection (anticipated removal of at least five nodes)
  • Written informed consent, including willingness to be randomized to morphine or regional analgesia

Exclusion Criteria:

  • Previous surgery for breast cancer (except diagnostic biopsies)
  • Inflammatory breast cancer
  • Age < 18 or > 85 years old
  • Scheduled free flap reconstruction
  • ASA Physical Status ≥ 4
  • Any contraindication to epidural or paravertebral anesthesia and analgesia (including coagulopathy, abnormal anatomy)
  • Any contraindication to midazolam, propofol, sevoflurane, fentanyl, or morphine
  • Other cancer not believed by the attending surgeon to be in long-term remission
  • Systemic disease believed by the attending surgeon to present ≥ 25% two-year mortality
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00418457

Contacts
Contact: Gretchen Upton, BA 216-444-3289 uptong@ccf.org

Locations
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Gretchen Upton, BA    216-444-3289    uptong@ccf.org   
Principal Investigator: Douglas Mayers, MD, PhD         
Sub-Investigator: Mark Krantz, MD         
Sub-Investigator: Michael Ritchie, MD         
Sub-Investigator: Alan Kuhel, MD         
Austria
Medical University of Vienna Recruiting
Vienna, Austria
Contact: Edith Fleischmann, MD       edith.fleischmann@meduniwien.ac.at   
Principal Investigator: Edith Fleischmann, MD         
Germany
University of Düsseldorf Recruiting
Düsseldorf, Germany, 40225
Contact: Tanja A. Meyer-Treschan, M.D.    49 (0) 211 81 17491    Tanja.Treschan@med.uni-duesseldorf.de   
Contact: Kathrin Domagala       kashia@gmx.li   
Principal Investigator: Tanja A Meyer-Treschan, M.D.         
Ireland
Mater Misericordiae Hospital Recruiting
Dublin, Ireland, 7
Contact: Donal J Buggy, MD,FRCPI    35-31-830-9568    donal.buggy@nbsp.ie   
Principal Investigator: Donal J Buggy, MD         
Sponsors and Collaborators
Outcomes Research Consortium
Investigators
Principal Investigator: Daniel I Sessler, MD The Cleveland Clinic
  More Information

No publications provided

Responsible Party: Daniel I. Sessler, M.D., Principal Investigator, Outcomes Research Consortium
ClinicalTrials.gov Identifier: NCT00418457     History of Changes
Other Study ID Numbers: 06-692
Study First Received: January 3, 2007
Last Updated: January 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Outcomes Research Consortium:
Breast Cancer
Anesthesia; regional
cancer recurrence
Anesthesia; inhalational
Analgesia; opioid

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Recurrence
Neoplasms by Site
Breast Diseases
Skin Diseases
Disease Attributes
Pathologic Processes
Anesthetics
Sevoflurane
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Hematologic Agents
Anesthetics, Inhalation
Anesthetics, General

ClinicalTrials.gov processed this record on August 21, 2014