Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

The radiolabeled Tc-99 colloid or phytate (500 Mbq) will be injected into the primary tumor 2 hours before surgery. A localized scintiscan will then be performed to confirm the radiolabeling of the sentinel node before surgery and for documentation. Isosulphan blue dye will be injected subdermal (0.5ml) over the tumor and intraparenchymal (3-4ml) towards the axilla 10-15mins before incision.

Radio-guided sentinel node biopsy

Axillary sampling

Rajendra A Badwe, M.S.

The advent of mammography and increased awareness of breast cancer has resulted in detection of smaller tumors, the majority of which would not have had metastasized to the axillary lymph nodes. The sentinel node (SN) is presumably the first echelon node in the axillary basin to become involved with metastatic breast cancer cells. Sentinel node biopsy (SNB) in operable breast cancer has gained popularity since it promises to avoid treatment of the axilla when the nodes are negative for metastasis. Advances in technology (radio-guided SNB) is associated with a risk of false negative SN reporting in 4-12%. The consequence of leaving behind untreated positive non-sentinel nodes in the axilla is a potential risk for axillary recurrence. Axillary sampling is a simple and inexpensive procedure in which level I nodes are removed by a blind dissection. The investigators critically analyzed the efficacy of both the procedures separately in consecutive pilot studies i.e., targeted SNB versus blind axillary sampling. The current study is planned as a prospective comparison study where a patient undergoes both the procedures in the same surgical intervention and thus provides an immediate comparison of the two techniques with respect to their effectiveness.

Axillary node dissection in operable breast cancer provides an accurate way of staging the disease. With increased popularity of screening and earlier diagnosis, most women do not harbor axillary metastases, in which case, axillary lymph node dissection could be avoided. Sentinel node biopsy (SNB) gained rapid popularity because the technique could predict the presence of metastases in downstream lymph nodes, so that surgery and its associated morbidity could be safely avoided. SNB can be performed with injection of isosulphan blue subdermally and peritumorally alone or in combination with radio-guidance with technetium-99 labeled colloid injection. Radio-guided SNB is superior to the blue dye in identifying the SN, and a combined technique is still better. However, it failed to accomplish its objective in a proportion of cases where the sentinel node could not be identified even with expensive gadgetry like gamma probes. An overview of sentinel node studies showed that the node was found in only 85-90% of patients and the overall sensitivity in correctly predicting the negative axilla by sentinel node biopsy was only 94%. There was a false negative rate of 6.2% wherein the sentinel node was reported negative in presence of metastasis to non-sentinel nodes in axilla.

Axillary sampling was a forerunner to the targeted sentinel node biopsy. The main objective of axillary sampling at that time was to detect a positive axilla. More recently it is being tested as an accurate predictor of axillary status for absence of metastasis.

There is a definite learning curve in SNB with higher non-detection rates and false negative rate in the earlier phases of the study compared to the later part. This learning curve is absent in axillary sampling, which requires no specialized training or expensive equipment and has a 100% detection rate. The mean number of sentinel nodes that were identified, as reported in various SNB studies, was 2.13 (with a range of mean numbers of SN dissected being 1.3-3.1). The actual range of number of sentinel nodes dissected was 1 - 8, which is quite comparable to the average 4 -5 nodes that are required to be sampled for accurately predicting the axilla. Badwe and Mittra have concluded that sentinel node biopsy is expensive and is driven by lure for technology and fashion, and has little advantage over axillary node sampling in predicting a negative axilla.

There is a validation study of lower axillary sampling versus total axillary clearance reported by Steele et al in 1985 with a sensitivity of 100% and an accuracy of 99.5%. The more recent validation study of 5-node axillary sampling compared to level I-II dissection was reported from Stockholm on 416 operable breast cancer patients. The noteworthy finding was that in this study node sampling had a 100% yield, 97.3% sensitivity and a negative predictive value of 98.5% with a false negative rate of 2.7% in predicting the axilla. The comparative figures for SNB in the world overview are 94% sensitivity, 97% negative predictive value and a false negative rate of 6.5%.

Preliminary studies of SNB and axillary sampling at TMH Sentinel node biopsy by Isosulphan blue injection was performed as a validation pilot study at the Breast unit in TMH between April 1999 to November 2000 in 100 women with clinically node negative operable breast cancer. SN was found in 77% cases with a false negative rate of 16.6% and sensitivity of 76.1%. The procedure had a negative predictive value of 90.4% cases in predicting the rest of the axilla. The number of sentinel nodes dissected was 1-6 with an average of 1.4.

Axillary sampling was subsequently performed as a pilot study between May 2001 to August 2002 in 97 women with a similar clinical stage as above. Nodes were found in all patients (100%) in level I with a false negative reporting in 11% cases, sensitivity of 88.9%, negative predictive value of 100% and an average of 4 nodes dissected (range from 1-9).

In developing countries with limited resources, it may not be feasible for every institution to acquire a gamma probe. Axillary sampling may thus be a comparably cheaper and practical alternative to SNB. Axillary sampling and sentinel node biopsy should, however, be compared with respect to the resultant morbidity and false negative rates before adopting either method as standard clinical practice.

The Nottingham group have recently published the results of a prospective study to find out the value of adding SNB to 4-node axillary sampling (4NAS) within the same patient. Two hundred patients were accrued and 4NAS was found to have a lower false negative rate compared to SNB. We propose to compare the two procedures in a clinical trial with a comparison of respective false negative rates and sensitivity as the immediate end points.

Methodology:

Eligible women will be recruited in the study after obtaining an informed consent and centrally registered at the Clinical Research Secretariat at the Tata Memorial Hospital, Mumbai.

The radiolabeled Tc-99 colloid or phytate (500 Mbq) will be injected into the primary tumor 2 hours before surgery. A localized scintiscan will then be performed to confirm the radiolabeling of the sentinel node before surgery and for documentation. Isosulphan blue dye will be injected subdermal (0.5ml) over the tumor and intraparenchymal (3-4ml) towards the axilla 10-15mins before incision.

Axillary sampling will be performed first. A 2 cm incision will be made in the middle third of the proposed axillary clearance incision below the axillary hairline. All axillary fat and tissue in an area of 2cm diameter will be dissected out. The anterior limit of dissection is the posterior border of pectoralis major, the posterior limit of dissection is the anterior border of latissimus dorsi muscle, upper limit of dissection is the intercostobrachial nerve, and base is serratus anterior muscle on lateral chest wall. In those cases that undergo a mastectomy, the tissue in the axillary tail will be identified first and then removed as specified above.

After completion of sampling procedure, the remaining axillary tissue will be checked for any other node showing a blue discoloration or radioactivity and the same will be documented as found outside of axillary sampling. Axillary clearance will then be separately completed in all patients by standard technique after extending the incision without waiting for the frozen section report.

Sentinel Node Biopsy and Axillary Sampling in Operable Breast Cancer

Clinical Trial of Sentinel Node Biopsy Versus Axillary Sampling in Women With Clinically Node Negative Operable Breast Cancer

The patient enrolled on this study will be planned for surgery and outcome will be measured after avability of histo-pathological report.

Indian Council of Medical Research

Tata Memorial Hospital

Director

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Reproductive Control Agents

Paclitaxel

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Docetaxel

Albumin-Bound Paclitaxel

Anti-Bacterial Agents

Moxifloxacin

Antibiotics, Antitubercular

Taxane

Norgestimate, ethinyl estradiol drug combination

Ethinyl Estradiol

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Estradiol

Polyestradiol phosphate

Norgestimate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Contraceptive Agents

Contraceptive Agents, Hormonal

Contraceptives, Oral

Contraceptives, Oral, Combined

Contraceptive Agents, Female

Standard adjuvant chemotherapy (Taxanes combined with cyclophosphamide or doxorubicin combined with cyclophosphamide followed by taxanes) plus antibiotic (moxifloxacin)

Other Name: docetaxel 75mg/m\^2, or nab-paclitaxel 260mg/m\^2, IV, days 1, cycled every 21 days cyclophosphamide 1000 mg/m\^2, IV, days 1, cycled every 21 days; or doxorubicin 60mg/m\^2, IV, days 1, combined with cyclophosphamide 600 mg/m\^2, IV, days 1, followed by docetaxel 75mg/m\^2, or nab-paclitaxel 260mg/m\^2, IV, days 1; plus Moxifloxacin 0.4 PO once daily days 1-5; cycled every 21 days

Standard adjuvant chemotherapy (Docetaxel combined with cyclophosphamide or doxorubicin combined with cyclophosphamide followed by docetaxel) plus placebo

Other Name: docetaxel 75mg/m\^2, or nab-paclitaxel 260mg/m\^2, IV, days 1 cyclophosphamide 1000 mg/m\^2, IV, days 1, cycled every 21 days; or doxorubicin 60mg/m\^2, IV, days 1, combined with cyclophosphamide 600 mg/m\^2, IV, days 1, followed by docetaxel 75mg/m\^2, or nab-paclitaxel 260mg/m\^2, IV, days 1; plus Placebo 0.4 PO once daily days 1-5; cycled every 21 days

docetaxel 75mg/m\^2, or nab-paclitaxel 260mg/m\^2, IV, days 1 cyclophosphamide 1000 mg/m\^2, IV, days 1, cycled every 21 days; or doxorubicin 60mg/m\^2, IV, days 1, cycled every 21 days cyclophosphamide 600 mg/m\^2, IV, days 1, cycled every 21 days docetaxel 100 mg/m\^2, IV, days 1, cycled every 21 days; plus Moxifloxacin 0.4 PO once daily days 1-5; cycled every 21 days

standard adjuvant chemotherapy plus moxifloxacin

docetaxel 75mg/m\^2, or nab-paclitaxel 260mg/m\^2, IV, days 1 cyclophosphamide 1000 mg/m\^2, IV, days 1, cycled every 21 days; or doxorubicin 60mg/m\^2, IV, days 1, cycled every 21 days cyclophosphamide 600 mg/m\^2, IV, days 1, cycled every 21 days docetaxel 100 mg/m\^2, IV, days 1, cycled every 21 days; plus Placebo 0.4 PO once daily days 1-5; cycled every 21 days

standard adjuvant chemotherapy plus placebo

Zhongyu Yuan, Professor

Yuanyi Zhong, MD

Zhong-Yu Yuan, M.D.

The primary objective of this study is to compare disease-free survival (DFS) of patients with operable breast cancer randomised to treatment with standard adjuvant chemotherapy plus moxifloxacin or placebo.

This is a multicenter, randomised, double-blind, placebo-controlled, phase 3 clinical trial. The main purposes of this study are to examine the efficacy and safety of standard adjuvant chemotherapy plus moxifloxacin or placebo as care for patients with operable breast cancer. This study is designed to recruit up to 520 subjects.

Moxifloxacin in Adjuvant Treatment of Patients With Operable Breast Cancer

A Multicenter, Placebo-Controlled, Phase III Trial of Standard Adjuvant Chemotherapy Plus Moxifloxacin in Operable Breast Cancer

We decided to not share our individual participant data (IPD) to other researchers.

The interval from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death due to any cause

The interval from the date of randomization until the first date on death due to any cause, or the last follow-up time

The interval from the date of randomization until the first date on distant metastasis, death due to any cause, or second primary invasive breast cancer

Sun Yat-sen University

Professor of Medicine

Capecitabine

Fluorouracil

Epirubicin

Antimetabolites

Weekly Paclitaxel (WP) for 12 weeks followed by Fluorouracil + Epirubicin + Cyclophosphamide (FEC) every 3 weeks for 4 cycles

Docetaxel + Capecitabine (DX) days 1-14 every 3 weeks for 4 cycles followed by FEC for 4 cycles.

80 mg/m\^2 by vein (IV) Weekly Over 1 Hour x 12 Weeks

75 mg/m\^2 by vein (IV) Over 1 Hour Once Every 3 Weeks

1500 mg/m\^2 by mouth Twice Daily x 2 Weeks

Aman U. Buzdar, MD

Primary Objectives:

* Determine the impact of each regimen on the disease free and overall survival of patients with operable breast cancer.
* Determine the ability of docetaxel/capecitabine to downstage primary breast cancer when administered in the neoadjuvant setting when compared with weekly paclitaxel.
* Determine the ability of each regimen to enhance breast conservation therapy when administered in the neoadjuvant setting. (See protocol text for additional objectives and details).

Before the study, participants will have a complete physical exam, including blood tests and a chest x-ray. A mammogram and a sonogram of the breast and armpit will be done to record tumor size (for patients who have not had surgery). Sonography of the liver or a CT scan of the abdomen will also be done. In some patients who have not had surgery, 3-4 samples of the breast tumor will be taken to help confirm the diagnosis of breast cancer. A biopsy needle will be used to collect the samples.

During the study, participants will have blood tests done before each dose of chemotherapy. For participants who have not had surgery, a mammogram and sonogram will be done of the breast and armpit after completion of paclitaxel or docetaxel/capecitabine and after completion of fluorouracil, cyclophosphamide, and epirubicin (FEC). These studies will help doctors to keep track of the tumor size and help with the final decision whether to remove all or part of the breast and nearby lymph nodes after completion of chemotherapy.

Participants in this study will be randomly assigned (as in the toss of a coin) to one of two treatment groups. There is an equal chance of being in either group.

Participants in Group I will receive paclitaxel once a week. The drug will be given through a plastic tube in a vein over 1 hour for a total of 12 treatments. Before each treatment, patients will receive the drug Decadron (dexamethasone) through the vein and may receive Zofran (ondansetron), Benadryl (diphenhydramine hydrochloride) and/or cimetidine to help decrease the risk of side effects from paclitaxel.

Participants in Group II will receive docetaxel and capecitabine. Docetaxel will be given once every 3 weeks. Docetaxel will be given through a plastic tube in the vein over 1 hour. Capecitabine will be started the same day docetaxel is given. This medicine is given in a pill form. The doctor will prescribe a dose of these pills based upon body weight and height. Participants will take several pills two times a day for 14 days. Participants will then not take any capecitabine pills for one week, until the next dose of docetaxel is given. This combination of docetaxel and capecitabine will be given four times (over a period of 12 weeks). Before each treatment, patients will receive the drug Decadron (dexamethasone) by mouth.

After treatment with either paclitaxel or docetaxel/capecitabine, all participants will receive the drugs FEC through a plastic tube into a vein. All of these drugs will be given once every three weeks for a total of 4 treatments (12 weeks total). Decadron (dexamethasone), Zofran (ondansetron) and Benadryl (diphenhydramine hydrochloride) will be given before the chemotherapy to help decrease the risk of side effects.

Participants who have a Her-2/neu positive cancer will potentially be eligible to receive trastuzumab therapy for 1 year. This medicine is given through a vein either once a week (over 30 minutes) or once every 3 weeks (over 30 minutes). Your doctor will discuss whether this medicine is appropriate for you.

After all treatment is done, participants whose tumors are sensitive to hormones (estrogen) will take a pill to help decrease the amount of hormone (estrogen) that can reach any tumor cells. This pill will be taken once a day for 5 years.

Participants who have not completed surgery for their cancer before receiving the chemotherapy described above will have surgery to remove all or part of the breast that has cancer. If there are signs that the lymph nodes in the armpit (axilla) contain cancer, these lymph nodes will also be removed.

After chemotherapy and surgery, or after completion of chemotherapy (patients who had surgery done first), participants may then receive radiation treatment to the breast area and armpit once a day (Monday through Friday) for 5-6 weeks.

After the study, participants will return for checkups every 3-4 months during Years 1 and 2, every 6 months during years 3 and 4 and yearly after that. During the check-ups participants will talk with and be examined by their physician. Once a year, patients will have yearly mammograms (as needed), chest-x rays, and blood tests.

This is an investigational study. All of the drugs in this study are approved by the FDA for treatment of breast cancer. A total of 930 patients will take part in this study. All will be enrolled at M. D. Anderson.

Evaluation of Differing Taxanes/Taxane Combinations on the Outcome of Patients With Operable Breast Cancer

Percentage of participants where number with local recurrence, distant metastasis, or death of any cause at 50 months is divided by total number of participants and used as primary efficacy end point to compare paclitaxel to combination docetaxel and capecitabine in breast cancer treatment for preventing recurrence (return of cancer).

Safety of 2 Different Treatments determined by proportion of participants who achieved pathological complete response (pCR) between two different treatments; where pCR was defined as no histopathologic evidence of any residual invasive cancer cells in the breast and axillary lymph nodes.

Effectiveness defined as proportion of patients who were able to have breast conserving surgery (BCS) after preoperative therapy compared to total number of participants.

Roche Pharma AG

M.D. Anderson Cancer Center

Weekly Paclitaxel for 12 weeks followed by Fluorouracil + Epirubicin + Cyclophosphamide (FEC) every 3 weeks for 4 cycles

Weekly Paclitaxel (WP)

Docetaxel + Capecitabine days 1-14 every 3 weeks for 4 cycles followed by FEC for 4 cycles.

Docetaxel and Capecitabine (DX)

Total

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Aman Buzdar, M.D./Professor

(WP Arm):301 included in the intent to treat analysis and 297 included in the safety analysis.

(DX Arm):300 included in the intent to treat analysis and 292 included in the safety analysis.

Percentage of Participants With Reoccurrence

Proportion of Participants With Pathological Complete Response

Treatment Effectiveness at Eradicating Tumor in the Breast and Lymph Nodes

Overall Study

Carcinoma

Taken orally twice a day for 14 days and treatment will repeat every 21 days (1 cycle) for 4 cycles

Ian Krop, MD, PhD

The purpose of this study is to find out what effects (good and bad) taking capecitabine for 12 weeks before surgery will have on women with breast cancer.

* Prior to the start of treatment, patients will have a small metal clip inserted into the tumor bed to identify the tumor site to the surgeon. At that time, a needle biopsy of the breast tumor or a sentinel (underarm) lymph node biopsy will also be performed.
* Patients will take capecitabine orally twice daily for 14 days. This treatment will repeat every 21 days (1 cycle). Patients will receive 4 cycles of this treatment.
* A physical exam and blood work will be done every three weeks after starting therapy to monitor side effects.
* After two weeks of capecitabine a biopsy from the tumor will be done to generate information about the characteristics of the tumor that may respond to capecitabine.
* After completing 4 cycles (12 weeks) of capecitabine, patients will then undergo surgery to remove any remaining breast cancer (lumpectomy or mastectomy). Post-surgical treatment (radiation, chemotherapy, and hormonal therapy) is at the discretion of the patients physician.

Capecitabine in Women With Operable Breast Cancer

A Phase II Study of Preoperative Capecitabine in Women With Operable Breast Cancer

Hoffmann-La Roche

Beth Israel Deaconess Medical Center

Brigham and Women's Hospital

Dana-Farber Cancer Institute

Assistant Professor of Medicine

Hypoglycemic Agents

Trastuzumab

Metformin

Antineoplastic Agents, Immunological

Day 1: Liposome-encapsulated doxorubicin, 50 mg/m2 IV 1 hour infusion; Day 2 and 9: Docetaxel, 30 mg/m2 IV 1 hour infusion; Day 2, 9 and 16: Trastuzumab 4 mg/kg for the first infusion loading dose, then 2 mg/kg/week for subsequent injections.

Day -13 to 0: Metformin is administered as single agent. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10 Metformin 1000 mg will be administered twice a day continuously until end of the study treatment.

50 mg/m2 by intravenous infusion over a period of 1 hour on day 1 of each cycle repeated every 21 days. A final concentration of between 0.4 to 1.2 mg/ml doxorubicin hydrochloride, is required

30 mg/m2 by intravenous infusion over a period of 1 hour on day 2 and 9, every 3 week.They will be given for 6 cycles.

4 mg/kg for the first administration (day 2 cycle 1) and 2 mg/kg for subsequent administrations. Trastuzumab will be given weekly for the duration of chemotherapy (day 2, 9, 16), then will be administered at the dose of 6 mg/Kg every 3 weeks until completion of 52 weeks of treatment.

It is administered as single agent from day -13 to 0. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10, Metformin 1000 mg will be administered twice a day continuously until end of the study treatment.

Anna Fedeli, MD

It is a multicenter, open-label, two stage phase II trial, to assess activity, safety and potential early predictors of response in neoadjuvant setting. Patients with operable breast cancer (T1c and cytologically N1-2, or cT2-3, N0-N2, M0) or locally advanced breast cancer (T4a-d, N0-N2, M0) with overexpression or amplification of HER2 (AJCC 7th edition 2010) are included in the study.

The primary objective is to evaluate the pathological complete response rate (pCR).

The secondary objectives are:

* to evaluate the clinical response rate (RR).
* to evaluate the feasibility and systemic tolerance, with particular attention to cardiac toxicity.
* to evaluate the conservative surgery rate.

Total duration of the trial is 36 months; planned treatment are 6 cycles of chemotherapy. At every cycle (every 21 days) will be administered:

Day 1: Liposome-encapsulated doxorubicin, 50 mg/m2 IV 1 hour infusion; Day 2 and 9: Docetaxel, 30 mg/m2 IV 1 hour infusion; Day 2, 9 and 16: Trastuzumab 4 mg/kg for the first infusion loading dose, then 2 mg/kg/week for subsequent injections. Day -13 to 0: Metformin is administered as single agent. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10 Metformin 1000 mg will be administered twice a day continuously until end of the study treatment.

Multi-center, open-label phase II trial to assess activity of this chemotherapy scheme evaluated by pathologic complete response rate (pCR).

Planned treatment are 6 cycles of chemotherapy.

At every cycle (every 21 days) will be administered:

Day 1: Liposome-encapsulated doxorubicin, 50 mg/m2 IV 1 hour infusion; Day 2 and 9: Docetaxel, 30 mg/m2 IV 1 hour infusion; Day 2, 9 and 16: Trastuzumab 4 mg/kg for the first infusion loading dose, then 2 mg/kg/week for subsequent injections Day -13 to 0: Metformin is administered as single agent. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10 Metformin 1000 mg will be administered twice a day continuously until end of the study treatment.

Total duration of the trial: 36 months Enrollment period: 24 months Treatment: maximum of 6 cycles (5 months) per patient Follow-up for recurrence: every six months for 5 years, than once a year until 10 years after surgery.It's necessary to recruit 46 patients for clinical objectives evaluation.

A Study of Liposomal Doxorubicin + Docetaxel + Trastuzumab + Metformin in Operable and Locally Advanced HER2 Positive Breast Cancer

Clinical and Translational Phase II Study of Liposomal Doxorubicin Plus Docetaxel and Trastuzumab With Metformin as Primary Systemic Therapy for Operable and Locally Advanced Recombinant Human ErbB-2 (HER2) Positive Breast Cancer

Complete pathologic response will be defined as no invasive residuals in breast and axillary nodes. In situ tumor residuals are considered as complete response rate

The clinical response rate (RR) will be including Pathological Complete Response, Clinical Complete Response and Clinical Partial Response (Response Evaluation Criteria in Solid Tumors (RECIST) criteria).

All patients will be evaluable for toxicity from the time of their first treatment with Metformine. The toxicity will be recorded according to the CTC-AE, version 4.0 in the safety population until Follow-up is completed (36 months)

evaluation of the number of patients who underwent conservative surgery

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Herceptin starting 4 mg/kg intravenous (IV), then 2 mg/kg weekly for all other cycles neo-adjuvant chemotherapy and during FEC therapy for total 24 doses. Taxol 225 mg/m\^2 continuous IV over 24 hours each cycle; Fluorouracil 500 mg/m\^2 IV Days 1 at 3-4 week intervals; Cytoxan 500 mg/m\^2 IV on Day 1; Epirubicin 75 mg/m\^2 IV on Day 1. Four 21-day cycles.

Starting dose of 4 mg/kg by vein, then 2 mg/kg weekly after that until the end of all cycles of neo-adjuvant chemotherapy and during FEC therapy for a total of 24 doses.

Herceptin

225 mg/m\^2 by vein as a continuous infusion over 24 hours each cycle for a total of 4 cycles.

Taxol

500 mg/m\^2 by vein on Days 1 and 4 for 4 cycles at 3-4 week intervals.

500 mg/m\^2 on Day 1 of each cycle for 4 cycles.

Cytoxan

75 mg/m\^2 IV on Day 1 of each cycle for 4 cycles.

Aman U Buzdar, MD

The purpose of this study is to evaluate the addition of Herceptin to standard chemotherapy treatment of patients newly diagnosed with operable breast cancer.

Other objectives: 1) to evaluate the potential of this therapy to reduce the size of the tumor and increase the possibility of breast conservative surgery, 2) evaluate the ability of this regimen to prevent recurrence of breast cancer and impact on survival, 3) determine side effect profile with the addition of Herceptin, and 4) evaluate significance of HER2 expression by two different methods.

Participants will receive Herceptin in addition to chemotherapy with Taxol and FEC. 'FEC' is Fluorouracil, Cyclophosphamide and Epirubicin.

During the first course of therapy Herceptin will be given on day 1 through a needle in a vein over 90 minutes. Participants will then be observed for 1 hour after that for harmful side effects. If none occur, later doses of Herceptin will be given over 30 minutes instead of 90 minutes.

On day 2, participants will be given Taxol again through a needle in a vein over 24 hours. Participants will receive the drugs Decadron (dexamethasone), Benadryl (diphenhydramine) and Tagamet (cimetidine) prior to Taxol treatment to prevent allergic reaction due to Taxol. Participants will be observed for 1 hour after starting Taxol for harmful side effects. If none occur, both Taxol and Herceptin can be given on the same day on subsequent courses. Taxol will be premedicated with the same drugs on subsequent courses.

Participants will receive Herceptin weekly for 24 consecutive weeks. Taxol will be given to participants every 3 weeks for 4 courses.

Participants who get a fever or infection during treatment may be given the drug G-CSF. Granulocyte colony-stimulating factor (G-CSF or GCSF) stimulates the bone marrow to make white blood cells, which fight infections.

After Taxol treatment, all participants will receive the drugs fluorouracil, cyclophosphamide, and epirubicin (FEC) through a plastic tube in a vein. Fluorouracil will be given intravenously (IV) as a short infusion on days 1 and 4. Cyclophosphamide will be given intravenously as a short infusion on day 1. Epirubicin will be given IV on day 1. This FEC treatment will be repeated every 3 weeks for a total of 4 treatments. Participants will continue to receive Herceptin weekly during therapy with FEC.

After all FEC treatment is done and surgery is completed, patients with tumors that are sensitive to hormones will begin taking the drug tamoxifen and/or aromatase inhibitors if the patient is postmenopausal. The drug will be given as a pill once a day for 5 years.

Patients will then have surgery to remove all or part of the breast that has cancer. If there are signs that the lymph nodes in the armpit (axilla) contain cancer, these lymph nodes will be removed. Patients may then receive radiation treatment to the breast area and armpit once a day for six weeks.

During the study, participants will have blood tests once a week during the first course of treatment of both Taxol and FEC. In subsequent courses, blood tests will be done prior to administration of chemotherapy. A mammogram and a sonogram will be obtained after Taxol treatment and after FEC treatment. This will help doctors keep track of the tumor size and decide whether to remove all or part of the breast and nearby lymph nodes.

After the study, participants will return for checkups every 4 months during years 1 and 2, every 6 months during year 3, and once a year after that. At each visit, participants will have a complete exam including blood tests and a chest x-ray. Mammography will be done once a year.

Before the study, participants will have a complete exam including blood tests and a chest x-ray. A mammogram and a sonogram of the breast and armpit will be obtained to record tumor size. Small metal clips will be inserted into the breast to mark the tumor if the tumor is shrinking rapidly in response to therapy; in this way, if the tumor disappears after drug treatment, the surgeon can still remove the tissue around the tumor. Sonography of the liver or a CT scan of the abdomen will also be done. In some participants, 3-4 samples of the breast that has tumor will be taken. The samples will be taken using a biopsy needle. An echocardiogram (heart function test) will be done on every participant at baseline. An echocardiogram will be done after finishing their Taxol chemotherapy and another one after finishing FEC chemotherapy. Copies of the echocardiogram tapes may be sent to the sponsor for review. Women who are able to have children will have a pregnancy test.

After having completed therapy, all patients will have a follow-up evaluation of their heart function (same as baseline) 4 months or greater after last treatment.

This is an investigational study. Taxol and Herceptin and all other drugs used in this study are approved by the U. S. Food and Drug Administration. All patients will be treated in the MD Anderson Cancer Center outpatient clinic.

Evaluation of the Addition of Herceptin to Standard Chemotherapy in the Neoadjuvant Setting for Operable Breast Cancer

Response criteria for Complete Remission defined as disappearance of all clinical evidence of active tumor by clinical evaluation, mammogram and/or ultrasound, and free of all symptoms.

Genentech, Inc.

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

Lidocaine

Anesthetics

Anesthetics, Local

Sodium Channel Blockers

Diuretics, Potassium Sparing

: No peritumoral Local Anesthesia prior to excision

Arm A: 60mM of 0.5% Inj. Lignocaine will be injected peri tumoral prior to excision.

0.5% lignocaine 60mM

Rajendra A Badwe, MS

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)

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

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

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.

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)

Patient with complete pathological response

Patient with partial pathological response

To measure muscle mass and predict pCR to NAC and its effect on clinical outcomes.

Neoadjuvant therapy

Aysun Isiklar, M.D.

The investigators aimed to accurately measure muscle mass and predict pCR to NAC and its effect on clinical outcomes.

In patients with operable breast cancer (BC) receiving neoadjuvant chemotherapy (NAC), the pathological response rate was found to be related to body composition. The success of complete pathologic response (pCR) is a known prognostic factor in BC patients treated with NAC. The investigators aimed to accurately measure muscle mass and predict pCR to NAC and its effect on clinical outcomes.

Muscle Parameters and Pathological Response in Breast Cancer Patients

The Relation Between the Initial Value of the Skeletal Mass Index and Pathological Response

Residual cancer burden (RCB) is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy.

skeletal muscle area (cm2)/height (m2) et L3 level

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sentinel Node Biopsy and Axillary Sampling in Operable Breast Cancer	NCT00128362	Cancer of the B...	Radio-guided se... Axillary sampli...	18 Years - 70 Years	Tata Memorial Hospital
Moxifloxacin in Adjuvant Treatment of Patients With Operable Breast Cancer	NCT05114720	Breast Cancer	standard adjuva... standard adjuva...	18 Years - 70 Years	Sun Yat-sen University
Evaluation of Differing Taxanes/Taxane Combinations on the Outcome of Patients With Operable Breast Cancer	NCT00050167	Breast Cancer	Paclitaxel Docetaxel Capecitabine	-	M.D. Anderson Cancer Center
Capecitabine in Women With Operable Breast Cancer	NCT00148720	Invasive Breast... Primary Invasiv... Stage I Breast ... Stage II Breast... Stage III Breas...	Capecitabine	18 Years -	Dana-Farber Cancer Institute
A Study of Liposomal Doxorubicin + Docetaxel + Trastuzumab + Metformin in Operable and Locally Advanced HER2 Positive Breast Cancer	NCT02488564	HER-2 Positive ...	Liposomal doxor... Docetaxel Trastuzumab Metformin	18 Years - 75 Years	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Evaluation of the Addition of Herceptin to Standard Chemotherapy in the Neoadjuvant Setting for Operable Breast Cancer	NCT00038402	Breast Cancer	Herceptin Taxol Fluorouracil Cytoxan Epirubicin	-	M.D. Anderson Cancer Center
Randomized Controlled Trial to Assess Blockade of Voltage Gated Sodium Channels During Surgery in Operable Breast Cancer	NCT01916317	Operable Breast...	0.5% lignocaine...	18 Years - 99 Years	Tata Memorial Hospital
Muscle Parameters and Pathological Response in Breast Cancer Patients	NCT06151379	Neoadjuvant Che...	Neoadjuvant the...	29 Years - 72 Years	Acıbadem Atunizade Hospital
Moxifloxacin in Adjuvant Treatment of Patients With Operable Breast Cancer	NCT05114720	Breast Cancer	standard adjuva... standard adjuva...	18 Years - 70 Years	Sun Yat-sen University
Muscle Parameters and Pathological Response in Breast Cancer Patients	NCT06151379	Neoadjuvant Che...	Neoadjuvant the...	29 Years - 72 Years	Acıbadem Atunizade Hospital
Evaluation of Differing Taxanes/Taxane Combinations on the Outcome of Patients With Operable Breast Cancer	NCT00050167	Breast Cancer	Paclitaxel Docetaxel Capecitabine	-	M.D. Anderson Cancer Center
Evaluation of Differing Taxanes/Taxane Combinations on the Outcome of Patients With Operable Breast Cancer	NCT00050167	Breast Cancer	Paclitaxel Docetaxel Capecitabine	-	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for operable breast cancer