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Randomized Controlled Trial to Assess Blockade of Voltage Gated Sodium Channels During Surgery in Operable Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01916317
Recruitment Status : Active, not recruiting
First Posted : August 5, 2013
Last Update Posted : March 12, 2020
Sponsor:
Collaborators:
Shri Siddhivinayak Ganpati Cancer Hospital
Kolhapur Cancer Centre (KCC)
Max Super Speciality Hospital
Basavatarakam Indo- American Cancer Hospital (BIACH)
Malabar Cancer Centre (MCC)
North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS)
All India Institute of Medical Sciences, New Delhi
Gujarat Cancer and Research Institute (GCRI)
Sterling Multi Speciality Hospital (SMSH)
Dr. B Barooha Cancer Institute (BBCI)
Information provided by (Responsible Party):
Dr Rajendra A. Badwe, Tata Memorial Centre

Brief Summary:

Voltage Gated Sodium Channels Over the years, there is more evidence that ionic channels are involved in the oncogenic process. Among these, voltage gated sodium channels (VGSC) expressed in non-nervous or non-muscular organs are often associated with the metastatic behavior of different cancers.

Expression of VGSCs has been reported both in vitro and/or in vivo in a range of human carcinomas, including breast cancer Ion channels are major signaling molecules expressed in a wide variety of tissues. They are involved in determining a variety of cellular functions like proliferation, solute transport, volume control, enzyme activity, secretion, invasion, gene-expression, excitation-contraction coupling, and intercellular communication.4 VGSC activity contributes to much cellular behavior integral to metastasis, including cellular process extension, lateral motility and galvanotaxis, transverse invasion, and secretory membrane activity.

A correlation between Na transport and oncogenesis has been widely reported in literature. In 1980, transformed mouse mammary cells were shown to have 3-fold higher intra-cellular sodium content than untransformed cells.5 Additionally evidence suggest that increasing the inward sodium current through voltage gated sodium channels increased the invasive capacity of breast cancer.6 Also, growth and proliferation of mammary adenocarcinoma cells can be inhibited by Amiloride suggesting that epithelial Na channels (ENaC) activity is correlated with proliferation of breast cancer cells

Current evidence suggests that VGSC activity is necessary and sufficient for cancer cell invasiveness8. A recent in vitro study has shown that the human MDA MB 231 breast cancer cell line expressed functional VGSCs9. However, the molecular nature of the VGSC and its functional relevance to breast cancer in vivo are currently under study.

Surgical operations for cancer have been reported to induce dissemination of cancer cells into surrounding tissues or into the circulation10,11and infiltration anesthetics can inhibit immune response12-14. Although the mechanism remains to be elucidated, infiltration anesthetics such as lidocaine have membrane- stabilizing action (Seeman, 1972) and these agents could have direct effects on cancer cells. Therefore, it is important to clarify the effects of infiltration anesthetics on behavior of the tumor cells.

Commonly used local anesthetic agents inhibit the VGSCs and also possess a unique membrane stabilizing action through other unknown mechanisms. A study by Mammota et al 15 reported that lignocaine, effectively inhibited the invasive ability of human cancer (HT1080, HOS, and RPMI-7951) cells at concentrations used in surgical operations (5-20 mM). Lidocaine reduced the invasion ability of these cells by partly inhibiting the shedding of HB-EGF from the cell surface and modulation of intracellular Ca2+ concentration contributed to this action. In addition, lidocaine (5-30 mM) infiltrated around the inoculation site, inhibited pulmonary metastases of murine osteosarcoma (LM 8) cells in vivo.

Dose of lidocaine15:

40 mM (1%) lidocaine is usually used for infiltration anesthesia for surgical operations. Lower concentrations (1-20mM) of lidocaine were sufficient to suppress the invasive ability of cancer cells14. One mM lidocaine inhibited the invasive ability of HT1080 cells by about 50%, and 20 mM lidocaine inhibited the invasion ability completely. Lidocaine also inhibited dose-dependently the invasive ability of HOS and RPMI-7951 cells, although it was less effective on HOS cells. Lignocaine exerts its anesthetic action by obstructing the sodium channel 16 however, 10 mMof tetrodotoxin (TTX), a specific sodium channel inhibitor, had little effect on the invasive ability of HT1080 cells. Ten mM lidocaine-N-ethylbromide (NEB), which does not cross the cell membrane, also had little effect on the invasive ability of the cells.

Objectives

Primary Objective:

• To assess the in-vivo ability of local anesthetics agents like lignocaine to decrease the dissemination of cancer cells during surgery and improve the disease free interval

Secondary Objective

• To assess the in-vivo ability of local anesthetics agents like lignocaine on impacting long term survival.

Methodology / Treatment plan

The study drug (0.5% lidocaine 60mM) will be tested in the intraoperative setting prior to surgery will be tested in a randomized setting.:

Arm A: 60mM of 0.5% lignocaine will be injected peritumoral prior to excision. The local anesthetic should be injected on all 6 surfaces of the tumor and also within the tumor. Wait for 7 minutes for its action followed by surgery. (Intervention arm) Arm B: No injection of lignocaine prior to excision (Control arm)


Condition or disease Intervention/treatment Phase
Operable Breast Cancer Drug: 0.5% lignocaine 60mM Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial to Assess Blockade of Voltage Gated Sodium Channels During Surgery in Operable Breast Cancer
Actual Study Start Date : December 12, 2011
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Lidocaine

Arm Intervention/treatment
No Intervention: Arm B:Control
: No peritumoral Local Anesthesia prior to excision
Active Comparator: Arm A: Intervention
Arm A: 60mM of 0.5% Inj. Lignocaine will be injected peri tumoral prior to excision.
Drug: 0.5% lignocaine 60mM



Primary Outcome Measures :
  1. • To assess the in-vivo ability of local anesthetics agents like lignocaine to decrease the dissemination of cancer cells during surgery and improve the disease free interval [ Time Frame: 5 years after completion of accrual or after 538 documented events for recurrence whichever is earlier ]
    Disease Free Survival (DFS) will be calculated from the date of randomization to the date of local, regional or distant relapse or death from any cause and will be censored at the last date of follow up for the patients that are alive and disease free or have been lost to follow up


Secondary Outcome Measures :
  1. • To assess the in-vivo ability of local anesthetics agents like lignocaine on impacting long term survival [ Time Frame: At 5 years after completion of accrual ]
    Overall Survival (OS) will be calculated from the date of randomization to the date of death or censored at the date of last follow up for the patients who are alive or lost to follow up.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All women with operable breast cancer planned for upfront surgery
  2. Histologically proven or clinically suspicious breast cancer

Exclusion Criteria:

  1. Previous history of lumpectomy or incision biopsy
  2. Distant metastases
  3. Neoadjuvant Chemotherapy
  4. History of allergy to drugs (lignocaine)
  5. High risk factors precluding the use of lignocaine
  6. Previous history of cancer

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01916317


Locations
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India
Dr. B Barooha Cancer Institute
Guwahati, Assam, India, 781016
All India Institute of Medical Science
New Delhi, Delhi, India, 110029
Gujarat Cancer & Research Institute (GCRI)
Ahmedabad, Gujarat, India, 380 016
Malabar Cancer Centre
Kannur, Kerela, India, 670103
Kolhapur Cancer Centre PVT LTD
Kolhapur, Maharashtra, India, 416008
Tata Memorial Centre Mumbai
Mumbai, Maharashtra, India, 400012
Sterling Multi Speciality Hospital
Pune, Maharashtra, India, 411044
Shree Siddhivinayak Ganapti Cancer Hospital Sangli
Sangli, Maharashtra, India, 416410
North Eastern Indira Gandhi Regional Institute of Health & Medical Sciences (NEIGRIHMS)
Shillong, Meghalaya, India, 793012
Basavatarakam Indo- American Cancer Hospital
Hyderabad, Telangana, India, 500034
Max Super Speciality Hospital
Delhi, India, 110092
Sponsors and Collaborators
Tata Memorial Hospital
Shri Siddhivinayak Ganpati Cancer Hospital
Kolhapur Cancer Centre (KCC)
Max Super Speciality Hospital
Basavatarakam Indo- American Cancer Hospital (BIACH)
Malabar Cancer Centre (MCC)
North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS)
All India Institute of Medical Sciences, New Delhi
Gujarat Cancer and Research Institute (GCRI)
Sterling Multi Speciality Hospital (SMSH)
Dr. B Barooha Cancer Institute (BBCI)
Investigators
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Principal Investigator: Rajendra A Badwe, MS Director and professor, Surgical Oncology
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Responsible Party: Dr Rajendra A. Badwe, Director, Tata Memorial Centre
ClinicalTrials.gov Identifier: NCT01916317    
Other Study ID Numbers: TMH project 902
First Posted: August 5, 2013    Key Record Dates
Last Update Posted: March 12, 2020
Last Verified: March 2020
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lidocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action