Randomized Controlled Trial to Assess Blockade of Voltage Gated Sodium Channels During Surgery in Operable Breast Cancer
Information source: Tata Memorial Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Operable Breast Cancer
Intervention: 0.5% lignocaine 60mM (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Tata Memorial Hospital Official(s) and/or principal investigator(s): Rajendra A Badwe, MS, Principal Investigator, Affiliation: Director and professor, Surgical Oncology
Overall contact: Rohini Hawaldar, BSc DCM, Phone: 91-22-2416 8601, Email: rwhawaldar@gmail.com
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)
Clinical Details
Official title: Randomized Controlled Trial to Assess Blockade of Voltage Gated Sodium Channels During Surgery in Operable Breast Cancer
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: • 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 outcome: • To assess the in-vivo ability of local anesthetics agents like lignocaine on impacting long term survival
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
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
Locations and Contacts
Rohini Hawaldar, BSc DCM, Phone: 91-22-2416 8601, Email: rwhawaldar@gmail.com
Kolhapur Cancer Centre PVT LTD, Kolhapur, Maharashtra 416008, India; Recruiting Suraj B Pawar, MS. FICS, Phone: 91-231-2532034, Email: surajpawar2001@yahoo.co.in Suraj B Pawar, MS.FICS, Principal Investigator
Tata Memorial Centre Mumbai, Mumbai, Maharashtra 400012, India; Recruiting Rajendra A Badwe, MS, Phone: 91-022-24177000, Ext: 4265, Email: badwera@gmail.com Rajendra A Badwe, MS, Principal Investigator
Shree Siddhivinayak Ganapti Cancer Hospital Sangli, Sangli, Maharashtra 416410, India; Recruiting Priyadarshan V Chitale, MS, Phone: 91-9850057556, Email: priyadarshanchitle@hotmail.com Priyadarshan V Chitale, Principal Investigator
Additional Information
Starting date: December 2011
Last updated: June 10, 2014
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