Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Breast Cancer Shrinkage Modes After Neoadjuvant Chemotherapy With Whole-mount Serial Sections and Three-dimensional Pathological and MRI Reconstruction (BCSMANC)

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: NCT01917578
Recruitment Status : Unknown
Verified August 2013 by Yongsheng Wang, Shandong Cancer Hospital and Institute.
Recruitment status was:  Recruiting
First Posted : August 6, 2013
Last Update Posted : August 6, 2013
Sponsor:
Information provided by (Responsible Party):
Yongsheng Wang, Shandong Cancer Hospital and Institute

Brief Summary:
The main clinical goal of NAC is to down-stage the primary tumor for BCS,yet BCS after NAC has been associated with significantly higher ipsilateral breast tumor recurrences.The accuracy of breast tumor excision in BCS can dramatically reduce IBTR.The main reseason of IBTR might be the uncertain shrinkage modes of the breast cancer after NAC.This clinical trial is firstly carried out to make clear the shrinkage modes of the primary tumor after 3 cycles and whole cycles of NAC,respectively,with whole-mount serial section(WMSS) and three-dimensional(3D) pathological reconstruction of the residual tumor.The second objective is to investigate the predictive value of 3D MRI reconstruction for the shrinkage modes of the primary tumor after NAC.

Condition or disease Intervention/treatment Phase
Breast Cancer Device: Ultrasound Procedure: CNB Procedure: BCS, Modified Radical Mastectomy Device: Pathologic Large Tissue Selected Table Device: Leica TP1020 Device: Pathologic Large Tissue Embedded Table Device: Leica SM2000 R Procedure: HE Stain Device: CX22 Device: Epson V600 Device: MRI Procedure: Three-Dimensional Reconstruction Device: Mammography Drug: TAC,TC,TA,CAF,CEF Drug: AC-P,TEC,AC,TC,TCH,CEF,TAC,CAF Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Phase III Trail of Breast Cancer Shrinkage Modes After Neoadjuvant Chemotherapy With Whole-mount Serial Sections and Three-dimensional Pathological and MRI Reconstruction
Study Start Date : August 2008
Estimated Primary Completion Date : March 2014
Estimated Study Completion Date : July 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Half Cycles Group
Patients complete half of the whole cycles of neoadjuvant chemotherapy.
Device: Ultrasound
  1. Evaluation of the tumor size by sonography is performed before neoadjuvant chemotherapy and prior to surgery.
  2. Measurement of tumor size refers to WHO standards.
Other Name: GE LOGIQ C5

Procedure: CNB
Typically, the pretreatment tumor specimen will be a core needle biopsy. Because 15% to 28% of patients will have no residual tumor after NAT, it is important to have an adequate pretreatment sample in which an unequivocal diagnosis of invasive carcinoma is established and evaluation of hormone receptors and HER2/ neu status is completed before treatment.
Other Name: core needle biopsy

Procedure: BCS, Modified Radical Mastectomy
All patients after neoadjuvant chemotherapy are performed BCS and modified radical mastectomy.
Other Name: BCS: breast conservative surgery

Device: Pathologic Large Tissue Selected Table
  1. Pathologic large tissue selected table has obtained Chinese patent.Its license ID is CN101261200.
  2. Each piece of breast tissues by cutting with the table has 3mm thickness.

Device: Leica TP1020

Procedure:

  1. Alcohol 70 % 1h
  2. Alcohol 80 % 1h
  3. Alcohol 85 % 1h
  4. Alcohol 90 % 1h
  5. Alcohol 95 % 1h
  6. Alcohol Ⅰ 100 % 1h
  7. Alcohol Ⅱ 100 % 1h
  8. Xylene Ⅰ 2h
  9. Xylene Ⅱ 2h
  10. Xylene Ⅲ 2h
  11. Paraffin 6h
  12. Paraffin 6h
Other Name: Semi-enclosed Benchtop Tissue Processor Leica TP1020

Device: Pathologic Large Tissue Embedded Table
  1. The table is made of brass .It is applying for a chinese patent.
  2. The table can simultaneously embed 8 piece of breast tissues.

Device: Leica SM2000 R
Each of paraffin section has 4 um thickness.
Other Name: Sliding microtome Leica SM2000 R

Procedure: HE Stain

Procedure:

  1. Xylene Ⅰ 60℃ 15-20 minutes
  2. Xylene Ⅱ 60℃ 15-20 minutes
  3. Alcohol 100% Ⅰ 3-5 minutes
  4. Alcohol 100% Ⅱ 3-5 minutes
  5. Alcohol 95% Ⅱ 3-5 minutes
  6. Alcohol 90% Ⅱ 3-5 minutes
  7. Wash in running tap water for 3 minutes
  8. Hematoxylin 5-10 minutes
  9. Wash in running tap water for 3 minutes
  10. Differentiate in 1% acid alcohol for 30 seconds
  11. Wash in running tap water for 1 minute
  12. Bluing in 0.2% ammonia water for 30-60 seconds
  13. Wash in running tap water for 3 minutes
  14. Counterstain in eosin Y solution for 30-60 seconds
  15. Wash in running tap water for 1 minute
  16. Alcohol 90% Ⅱ 2-3 minutes
  17. Alcohol 95% Ⅱ 2-3 minutes
  18. Alcohol 100% Ⅱ 3-5 minutes
  19. Alcohol 100% Ⅱ 3-5 minutes
  20. Xylene Ⅲ 5-10 minutes
  21. Xylene Ⅳ 5-10 minutes
  22. Mounting with neutral resin

Device: CX22
The residual tumor areas are microscopically outlined on each slice by pathologist.
Other Name: Biological Microscope CX22(Olympus)

Device: Epson V600
  1. Each slice that has been microscopically outlined is scanned by Epson V600.
  2. Every image by scanning should be saved as JPG.
Other Name: Epson Perfection V600 Photo Scanner

Procedure: Three-Dimensional Reconstruction

A.Pathological images three-dimensional reconstruction:

  1. Pathological images registration is based on skin and shear mark by Photoshop 13.0 software.
  2. Residual tumor boundary on Pathological images after registration are outlined and taken three-dimensional reconstruction by 3D-doctor 4.0 software.
  3. Observe the shrinkage modes in three-dimensional space.
  4. According to WHO standard,the boundaries of all residual tumor images are displayed in one plane and the longest diameter and its longest perpendicular diameter of boundaries are measured in one-dimensional space.
  5. According to RECIST standard,the longest diameter of boundaries of residual tumor images in three-dimensional space.

B.MRI images three-dimensional reconstruction:the procedure is similar to Pathological images three-dimensional reconstruction


Device: Mammography
  1. Evaluation of the tumor size by mammography is performed before neoadjuvant chemotherapy and prior to surgery.
  2. Measurement of tumor size and calcification extent refers to WHO standards.
  3. Calcification extent is not only measured in mammography image but also under microscope.
Other Name: GE Mammography

Drug: TAC,TC,TA,CAF,CEF
  1. TAC:Docetaxel 75 mg/㎡ iv day 1 + Doxorubicin 50 mg/㎡ in day 1 + Cyclophosphamide 500 mg/㎡ iv day 1(Cycled every 21 days for 3 cycles)
  2. TC:Docetaxel 75 mg/㎡ iv day 1 + Cyclophosphamide 600 mg/㎡in day 1(Cycled every 21 days for 2 cycles)
  3. TA:Docetaxel 75 mg/㎡ iv day 1 + Doxorubicin 50 mg/㎡ in day 1(Cycled every 21 days for 2 cycles)
  4. CAF:Cyclophosphamide 100 mg/㎡ po days 1-14 + Doxorubicin 30 mg/㎡ iv days 1,8 +5-fluorouracil 500 mg/㎡ iv days 1,8(cycled every 28 days for 3 cycles)
  5. CEF:Cyclophosphamide 75 mg/㎡ po day 1-14 + Epirubicin 60 mg/㎡ iv days 1,8 + 5-fluorouracil 500mg/㎡ iv days 1,8(cycled every 28 days for 3 cycles)
Other Names:
  • 1.TAC(docetaxel/doxorubicin/cyclophosphamide)
  • 2.TC(docetaxel/cyclophosphamide)
  • 3.TA(paclitaxel/doxorubicin)
  • 4.CAF(fluorouracil/doxorubicin/cyclophosphamide)
  • 5.CEF(cyclophosphamide/epirubicin//fluorouracil)

Experimental: Whole Cycles Group
Patients complete whole cycles of neoadjuvant chemotherapy.
Device: Ultrasound
  1. Evaluation of the tumor size by sonography is performed before neoadjuvant chemotherapy and prior to surgery.
  2. Measurement of tumor size refers to WHO standards.
Other Name: GE LOGIQ C5

Procedure: CNB
Typically, the pretreatment tumor specimen will be a core needle biopsy. Because 15% to 28% of patients will have no residual tumor after NAT, it is important to have an adequate pretreatment sample in which an unequivocal diagnosis of invasive carcinoma is established and evaluation of hormone receptors and HER2/ neu status is completed before treatment.
Other Name: core needle biopsy

Procedure: BCS, Modified Radical Mastectomy
All patients after neoadjuvant chemotherapy are performed BCS and modified radical mastectomy.
Other Name: BCS: breast conservative surgery

Device: Pathologic Large Tissue Selected Table
  1. Pathologic large tissue selected table has obtained Chinese patent.Its license ID is CN101261200.
  2. Each piece of breast tissues by cutting with the table has 3mm thickness.

Device: Leica TP1020

Procedure:

  1. Alcohol 70 % 1h
  2. Alcohol 80 % 1h
  3. Alcohol 85 % 1h
  4. Alcohol 90 % 1h
  5. Alcohol 95 % 1h
  6. Alcohol Ⅰ 100 % 1h
  7. Alcohol Ⅱ 100 % 1h
  8. Xylene Ⅰ 2h
  9. Xylene Ⅱ 2h
  10. Xylene Ⅲ 2h
  11. Paraffin 6h
  12. Paraffin 6h
Other Name: Semi-enclosed Benchtop Tissue Processor Leica TP1020

Device: Pathologic Large Tissue Embedded Table
  1. The table is made of brass .It is applying for a chinese patent.
  2. The table can simultaneously embed 8 piece of breast tissues.

Device: Leica SM2000 R
Each of paraffin section has 4 um thickness.
Other Name: Sliding microtome Leica SM2000 R

Procedure: HE Stain

Procedure:

  1. Xylene Ⅰ 60℃ 15-20 minutes
  2. Xylene Ⅱ 60℃ 15-20 minutes
  3. Alcohol 100% Ⅰ 3-5 minutes
  4. Alcohol 100% Ⅱ 3-5 minutes
  5. Alcohol 95% Ⅱ 3-5 minutes
  6. Alcohol 90% Ⅱ 3-5 minutes
  7. Wash in running tap water for 3 minutes
  8. Hematoxylin 5-10 minutes
  9. Wash in running tap water for 3 minutes
  10. Differentiate in 1% acid alcohol for 30 seconds
  11. Wash in running tap water for 1 minute
  12. Bluing in 0.2% ammonia water for 30-60 seconds
  13. Wash in running tap water for 3 minutes
  14. Counterstain in eosin Y solution for 30-60 seconds
  15. Wash in running tap water for 1 minute
  16. Alcohol 90% Ⅱ 2-3 minutes
  17. Alcohol 95% Ⅱ 2-3 minutes
  18. Alcohol 100% Ⅱ 3-5 minutes
  19. Alcohol 100% Ⅱ 3-5 minutes
  20. Xylene Ⅲ 5-10 minutes
  21. Xylene Ⅳ 5-10 minutes
  22. Mounting with neutral resin

Device: CX22
The residual tumor areas are microscopically outlined on each slice by pathologist.
Other Name: Biological Microscope CX22(Olympus)

Device: Epson V600
  1. Each slice that has been microscopically outlined is scanned by Epson V600.
  2. Every image by scanning should be saved as JPG.
Other Name: Epson Perfection V600 Photo Scanner

Device: MRI
  1. Evaluation of the tumor size by MRI was performed before neoadjuvant chemotherapy and prior to surgery.
  2. Measurement of tumor size refers to WHO standards.
  3. The images of patients which were scanned by MRI should be burned onto disc for 3d reconstruction.
Other Name: Philips Achieva 3.0T MRI System

Procedure: Three-Dimensional Reconstruction

A.Pathological images three-dimensional reconstruction:

  1. Pathological images registration is based on skin and shear mark by Photoshop 13.0 software.
  2. Residual tumor boundary on Pathological images after registration are outlined and taken three-dimensional reconstruction by 3D-doctor 4.0 software.
  3. Observe the shrinkage modes in three-dimensional space.
  4. According to WHO standard,the boundaries of all residual tumor images are displayed in one plane and the longest diameter and its longest perpendicular diameter of boundaries are measured in one-dimensional space.
  5. According to RECIST standard,the longest diameter of boundaries of residual tumor images in three-dimensional space.

B.MRI images three-dimensional reconstruction:the procedure is similar to Pathological images three-dimensional reconstruction


Device: Mammography
  1. Evaluation of the tumor size by mammography is performed before neoadjuvant chemotherapy and prior to surgery.
  2. Measurement of tumor size and calcification extent refers to WHO standards.
  3. Calcification extent is not only measured in mammography image but also under microscope.
Other Name: GE Mammography

Drug: AC-P,TEC,AC,TC,TCH,CEF,TAC,CAF
  1. AC-P:Doxorubicin 60 mg/㎡ iv day 1 +Cyclophosphamide 600 mg/㎡ iv day 1(Cycled every 14 days for 4 cycles)→ Paclitaxel 175mg/㎡ by 3h iv infusion day 1(Cycled every 14 days for 4 cycles) or Paclitaxel 80mg/㎡ by 1h iv infusion weekly for 12 wks.
  2. TEC:Docetaxel 75 mg/㎡ iv day 1 + Epirubicin 75 mg/㎡ in day 1 + Cyclophosphamide 500 mg/㎡ iv day 1(Cycled every 21 days for 6 cycles)
  3. AC:Doxorubicin 60 mg/㎡ in day 1 + Cyclophosphamide 600 mg/㎡ iv day 1(Cycled every 21 days for 4 cycles)
  4. TC:Docetaxel 75 mg/㎡ iv day 1 + Cyclophosphamide 600 mg/㎡in day 1(Cycled every 21 days for 4 cycles)
  5. TCH:Docetaxel 75 mg/㎡ iv day 1 + Carboplatin AUC 6 iv day1(Cycled every 21 days for 6 cycles) + Trastuzumab 4 mg/kg iv wk 1 → Trastuzumab 2 mg/kg iv for 17 wks → Trastuzumab 6 mg/kg iv every 3 wks to complete 1 year.
  6. CEF:Cyclophosphamide 75 mg/㎡ po day 1-14 + Epirubicin 60 mg/㎡ iv days 1,8 + 5-fluorouracil 500mg/㎡ iv days 1,8(cycled every 28 days for 6 cycles)
Other Names:
  • 1.AC(doxorubicin/cyclophosphamide)-P(paclitaxel)
  • 2.TEC(docetaxel/epirubicin/cyclophosphamide)
  • 3.AC(doxorubicin/cyclophosphamide)-T(docetaxel)
  • 4.TC(docetaxel/cyclophosphamide)
  • 5.TCH(docetaxel/carboplatin/trastuzumab)
  • 6.CEF(cyclophosphamide/epirubicin/fluorouracil)
  • 7.TAC(docetaxel/doxorubicin/cyclophosphamide)
  • 8.CAF(fluorouracil/doxorubicin/cyclophosphamide)




Primary Outcome Measures :
  1. The shrinkage modes of breast tumor after NAC. [ Time Frame: 6 year ]
    The tumor shrinkage modes of the primary tumor in patients with locally advanced breast cancer after 3 cycles and whole cycles of neoadjuvant chemotherapy(NAC).


Secondary Outcome Measures :
  1. The WMSS and 3D pathological reconstruction of the residual tumors after NAC. [ Time Frame: 6 year ]
    The whole-mount serial section(WMSS) and three-dimensional(3D) pathological reconstruction of the residual tumors after NAC.


Other Outcome Measures:
  1. The predictive value of 3D MRI reconstruction for the shrinkage modes of primary tumor after NAC. [ Time Frame: 4 year ]
    The predictive value of 3D MRI reconstruction for the shrinkage modes of the primary tumor after whole cycles of NAC.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Female patients,locally advanced breast cancer,age ≥18 years.
  2. Histologically confirmed invasive adenocarcinoma of the breast.
  3. Primary palpable disease confined to a breast and axilla on physical examination. For patients without clinically suspicious axillary adenopathy, the primary tumor must be larger than 2 cm in diameter by physical exam or imaging studies (clinical T2-T3, N0-N1, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-3, N1-2, M0). (T1N0M0 lesions are excluded.)
  4. Patients without clearly defined palpable breast mass or axillary lymph nodes but radiographically measurable tumor masses are acceptable. Accepted procedures for measuring breast disease are mammography, MRI, and breast ultrasound. This will need to be re-evaluated after 3 cycles and prior to surgery.
  5. ECOG 0 or 2
  6. No distant metastasis, as documented by complete staging workup ≤6 weeks prior to initiation of study treatment.
  7. No previous treatment for breast cancer.
  8. Adequate hematologic function with:

    Absolute neutrophil count (ANC) >1500/μL. Platelets ≥100,000/μL. Hemoglobin ≥10 g/dL.

  9. Adequate hepatic function with:

    Serum bilirubin ≤ the institutional upper limit of normal (ULN). Aspartate aminotransferase (AST) ≤2.5 x institutional ULN. Alanine aminotransferase (ALT) ≤2.5 x institutional ULN.

  10. Adequate renal function with serum creatinine ≤1.5 x ULN.
  11. Planned primary systemic (neoadjuvant) chemotherapy and surgical resection of residual primary tumor (mastectomy or lumpectomy/breast conservation) following completion of neoadjuvant chemotherapy

Exclusion Criteria:

  1. inflammatory breast cancer
  2. Pregnancy or breast-feeding.A negative serum pregnancy test within 7 days prior to first study treatment (Day 1, Cycle 1) for all women of childbearing potential is required. Patients of childbearing potential must agree to use a birth control method that is approved by their study physician while receiving study treatment and for 3 weeks after their last dose of study treatment. Patients must agree to not breast-feed while receiving study treatment.
  3. Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Patients must have discontinued use of such agents prior to beginning study treatment.
  4. Uncontrolled intercurrent illness including (but not limited to) ongoing or active infection.
  5. Concurrent treatment with any anti-cancer therapy other than those agents used in this study.
  6. Mental condition or psychiatric disorder that would prevent patient comprehension of the nature, scope, and possible consequences of the study or that would limit compliance with study requirements.

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): NCT01917578


Contacts
Layout table for location contacts
Contact: Yong-sheng Wang, MD +8613505409989 wangysh2008@aliyun.com
Contact: Tao Yang, MD +8618264190568 yangtao133252@aliyun.com

Locations
Layout table for location information
China, Shandong
Shandong Cancer Hospital Recruiting
Jinan, Shandong, China, 250117
Contact: Yong-sheng Wang, MD    +8613505409989    wangysh2008@aliyun.com   
Contact: Tao Yang, MD    +8618264190568    yangtao133252@aliyun.com   
Principal Investigator: Yong-sheng Wang, MD         
Principal Investigator: Tao Yang, MD         
Sponsors and Collaborators
Shandong Cancer Hospital and Institute
Investigators
Layout table for investigator information
Study Chair: Yong-sheng Wang, MD Shandong Cancer Hospital
Principal Investigator: Tao Yang, MD Shandong Cancer Hospital

Publications of Results:
Y-S Wang, Z-P Zhang, G Liu, D-B Mu, and X-Y Sun.Study of Breast Cancer Shrinkage Modes After Neoadjuvant Chemotherapy With Whole-mount Serial Sections and Three-dimensional Pathological and MRI Reconstruction. Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-17.

Layout table for additonal information
Responsible Party: Yongsheng Wang, Director, Head of Breast Cancer Center, Principal Investigator, Clinical Professor, Shandong Cancer Hospital and Institute
ClinicalTrials.gov Identifier: NCT01917578     History of Changes
Other Study ID Numbers: BCSMANC001
First Posted: August 6, 2013    Key Record Dates
Last Update Posted: August 6, 2013
Last Verified: August 2013

Keywords provided by Yongsheng Wang, Shandong Cancer Hospital and Institute:
Breast Cancer
shrinkage modes
three-dimensional reconstruction
neoadjuvant chemotherapy
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Docetaxel
Albumin-Bound Paclitaxel
Cyclophosphamide
Carboplatin
Doxorubicin
Liposomal doxorubicin
Trastuzumab
Fluorouracil
Epirubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors