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Phase II Trial of Neoadjuvant Metronomic Chemotherapy in Triple-Negative Breast Cancer

Primary Purpose

Breast Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Doxorubicin / Cyclophosphamide / Paclitaxel / Carboplatin

Definitive Surgery

Radiotherapy

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Triple negative (ER/PR negative; HER2 negative)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Women with Estrogen Receptor (ER), Progesterone Receptor (PR),and HER2 negative invasive breast cancer confirmed on core biopsy.(Note: HER2 negative by FISH preferred; HER2 0 or 1+ by IHC acceptable)
Primary tumor size 2cm or greater by physical exam or radiographic measurements.(Note: Locally advanced T4 or inflammatory breast cancer is eligible.)
Assessment of pre-treatment axillary lymph nodal status (Note: FNA biopsy if palpable or sentinel lymph node biopsy (SLNB) if not palpable preferred; clinical exam acceptable.)
Absolute neutrophil count > 1500 mm3 and platelet count > 100,000 mm3
Normal myocardial left ventricular function
Serum creatinine < 2.0 mg/dl
Total bilirubin and AST < 3X upper limits normal

Exclusion Criteria:

Recurrent or metastatic breast cancer findings (Note: If oncologically felt to be a second breast primary, patient eligible for this protocol)
Another active cancer present
Medical contraindications to chemotherapy or surgery
First trimester pregnancy
Breast feeding

Sites / Locations

Brody School of Medicine at East Carolina University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant metronomic AC followed by weekly TC

Arm Description

Neoadjuvant chemotherapy with metronomic AC followed by weekly TC then surgery

Outcomes

Primary Outcome Measures

1) Pathologic Response

Pathologic measurement post-surgery viable primary tumor mass

Secondary Outcome Measures

Full Information

NCT ID

NCT00542191

First Posted

October 9, 2007

Last Updated

May 4, 2021

Sponsor

Leo W. Jenkins Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT00542191

Brief Title

Phase II Trial of Neoadjuvant Metronomic Chemotherapy in Triple-Negative Breast Cancer

Official Title

Phase II Trial of Neoadjuvant Metronomic Chemotherapy in Triple-Negative Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Terminated

Why Stopped

Enrollment Completed

Study Start Date

July 2007 (undefined)

Primary Completion Date

August 2, 2016 (Actual)

Study Completion Date

August 2, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Leo W. Jenkins Cancer Center

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This neoadjuvant chemotherapy protocol focusing on "triple-negative" breast cancers alone will gather a foundation of primary tumor and axillary lymph nodal response to primary chemotherapy and ongoing correlated disease-free (DFS) and overall survival (OS) outcome data. This comparative data can then be used in building subsequent trials.

Detailed Description

Women with a diagnosed "triple-negative" proxy of basal-like breast cancer confirmed on a core biopsy and larger than 2 cm will be treated neoadjuvantly with the Livingston metronomic regimen of 12 weeks of weekly doxorubicin 24 mg/m2 and daily oral cyclophosphamide 60 mg/m2 followed by 12 successive weeks of taxol 80 mg/m2 and carboplatin AUC 2. Although clinical response will be evaluated prior to surgery, the primary end-point is the pathologic response. Secondary end-points will be DFS and OS based upon standard of care surveillance. A pathologic complete response (pCR) will require no histologic evidence of residual malignant cells seen in the primary tumor area specimen or the lymph nodes. Standard of care surgery and radiation therapy will be undertaken.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

Triple negative (ER/PR negative; HER2 negative)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant metronomic AC followed by weekly TC

Arm Type

Experimental

Arm Description

Neoadjuvant chemotherapy with metronomic AC followed by weekly TC then surgery

Intervention Type

Drug

Intervention Name(s)

Doxorubicin / Cyclophosphamide / Paclitaxel / Carboplatin

Other Intervention Name(s)

Metronomic

Intervention Description

DOXORUBICIN 24mg/m2 IV plus CYCLOPHOSPHAMIDE 60mg/m2 PO weekly x 12 successive weeks followed by PACLITAXEL 80mg/m2 IV over 1 hour plus CARBOPLATIN AUC 2 IV weekly x 12 successive weeks

Intervention Type

Procedure

Intervention Name(s)

Definitive Surgery

Intervention Description

Standard of care definitive surgery as determined by medical provider

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Intervention Description

Standard of care RADIATION THERAPY as indicated

Primary Outcome Measure Information:

Title

1) Pathologic Response

Description

Pathologic measurement post-surgery viable primary tumor mass

Time Frame

Upon completion therapy after surgery

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Women with Estrogen Receptor (ER), Progesterone Receptor (PR),and HER2 negative invasive breast cancer confirmed on core biopsy.(Note: HER2 negative by FISH preferred; HER2 0 or 1+ by IHC acceptable) Primary tumor size 2cm or greater by physical exam or radiographic measurements.(Note: Locally advanced T4 or inflammatory breast cancer is eligible.) Assessment of pre-treatment axillary lymph nodal status (Note: FNA biopsy if palpable or sentinel lymph node biopsy (SLNB) if not palpable preferred; clinical exam acceptable.) Absolute neutrophil count > 1500 mm3 and platelet count > 100,000 mm3 Normal myocardial left ventricular function Serum creatinine < 2.0 mg/dl Total bilirubin and AST < 3X upper limits normal Exclusion Criteria: Recurrent or metastatic breast cancer findings (Note: If oncologically felt to be a second breast primary, patient eligible for this protocol) Another active cancer present Medical contraindications to chemotherapy or surgery First trimester pregnancy Breast feeding

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paul Walker, MD

Organizational Affiliation

Brody School of Medicine at East Carolina University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Brody School of Medicine at East Carolina University

City

Greenville

State/Province

North Carolina

ZIP/Postal Code

27834

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

11553815

Citation

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lonning PE, Borresen-Dale AL. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74. doi: 10.1073/pnas.191367098.

Results Reference

background

PubMed Identifier

10963602

Citation

Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature. 2000 Aug 17;406(6797):747-52. doi: 10.1038/35021093.

Results Reference

background

PubMed Identifier

12917485

Citation

Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A, Martiat P, Fox SB, Harris AL, Liu ET. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10393-8. doi: 10.1073/pnas.1732912100. Epub 2003 Aug 13.

Results Reference

background

PubMed Identifier

16145060

Citation

Brenton JD, Carey LA, Ahmed AA, Caldas C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 2005 Oct 10;23(29):7350-60. doi: 10.1200/JCO.2005.03.3845. Epub 2005 Sep 6.

Results Reference

background

PubMed Identifier

15328174

Citation

Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, Akslen LA, Ragaz J, Gown AM, Gilks CB, van de Rijn M, Perou CM. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004 Aug 15;10(16):5367-74. doi: 10.1158/1078-0432.CCR-04-0220.

Results Reference

background

PubMed Identifier

15701700

Citation

Chang HY, Nuyten DS, Sneddon JB, Hastie T, Tibshirani R, Sorlie T, Dai H, He YD, van't Veer LJ, Bartelink H, van de Rijn M, Brown PO, van de Vijver MJ. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3738-43. doi: 10.1073/pnas.0409462102. Epub 2005 Feb 8.

Results Reference

background

PubMed Identifier

15510162

Citation

Turner N, Tutt A, Ashworth A. Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev Cancer. 2004 Oct;4(10):814-9. doi: 10.1038/nrc1457.

Results Reference

background

PubMed Identifier

16757721

Citation

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006 Jun 7;295(21):2492-502. doi: 10.1001/jama.295.21.2492.

Results Reference

background

PubMed Identifier

16609087

Citation

Berry DA, Cirrincione C, Henderson IC, Citron ML, Budman DR, Goldstein LJ, Martino S, Perez EA, Muss HB, Norton L, Hudis C, Winer EP. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA. 2006 Apr 12;295(14):1658-67. doi: 10.1001/jama.295.14.1658. Erratum In: JAMA. 2006 May 24;295(20):2356.

Results Reference

background

PubMed Identifier

15547178

Citation

Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP. The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst. 2004 Nov 17;96(22):1659-68. doi: 10.1093/jnci/djh312.

Results Reference

background

PubMed Identifier

11863092

Citation

Kerbel RS, Klement G, Pritchard KI, Kamen B. Continuous low-dose anti-angiogenic/ metronomic chemotherapy: from the research laboratory into the oncology clinic. Ann Oncol. 2002 Jan;13(1):12-5. doi: 10.1093/annonc/mdf093. No abstract available.

Results Reference

background

PubMed Identifier

16782917

Citation

Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2786-92. doi: 10.1200/JCO.2005.04.1764.

Results Reference

background

PubMed Identifier

16381626

Citation

Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, Loprinzi CL, Flynn PJ, Mailliard JA, Kardinal CG, Krook JE, Thrower AR, Visscher DW, Jenkins RB. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005 Dec;6(5):425-32. doi: 10.3816/CBC.2005.n.047.

Results Reference

background

PubMed Identifier

16622270

Citation

Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, Blohmer JU, Eiermann W, Jackesz R, Jonat W, Lebeau A, Loibl S, Miller W, Seeber S, Semiglazov V, Smith R, Souchon R, Stearns V, Untch M, von Minckwitz G. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006 Apr 20;24(12):1940-9. doi: 10.1200/JCO.2005.02.6187. Erratum In: J Clin Oncol. 2006 Jul 1;24(19):3221.

Results Reference

background

PubMed Identifier

16361629

Citation

Hennessy BT, Hortobagyi GN, Rouzier R, Kuerer H, Sneige N, Buzdar AU, Kau SW, Fornage B, Sahin A, Broglio K, Singletary SE, Valero V. Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol. 2005 Dec 20;23(36):9304-11. doi: 10.1200/JCO.2005.02.5023.

Results Reference

background

PubMed Identifier

15738535

Citation

Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. doi: 10.1200/JCO.2005.07.032. Epub 2005 Feb 28.

Results Reference

background

Citation

Rouzier R, Anderson K, Hess KR, et al: Basal and luminal types of breast cancer defined by gene expression patterns respond differently to neoadjuvant chemotherapy. San Antonio Breast Cancer Symposium. San Antonio, TX, 2004 (abstr 1023)

Results Reference

background

Citation

Carey LA, Dees EC, Sawyer L, et al: The triple negative paradox: Primary tumor chemosensitivity of the basal-like breast cancer (BBC) phenotype. San Antonio Breast Cancer Symposium. San Antonio, TX, 2004 (abstr 1023)

Results Reference

background

Citation

Jacquemier J, Penault-Llorca F, Mnif H, et al: Identification of a basal-like subtype and comparative effect of epirubicin-based chemotherapy and sequential epirubicin followed by docetaxel chemotherapy in the PACS 01 breast cancer trial: 33 markers studied on tissue microarrays (TMA). J Clin Oncol 2006 (suppl; abstr 509)

Results Reference

background

Citation

Hudis C, Citron M, Berry D, et al: Five-year follow-up of INT C9741: dose-dense chemotherapy is safe and effective. San Antonio Breast Cancer Symposium. San Antonio, TX, 2005 (abstr 41)

Results Reference

background

Citation

Ellis GK, Livingston RB, Rinn K, et al: Pilot adjuvant study: 12 weeks of dose dense doxorubicin with scheduled G-CSF support followed by 4 cycles of docetaxel. J Clin Oncol 2003 (suppl; abstr 148)

Results Reference

background

PubMed Identifier

21220618

Citation

Ellis GK, Barlow WE, Gralow JR, Hortobagyi GN, Russell CA, Royce ME, Perez EA, Lew D, Livingston RB. Phase III comparison of standard doxorubicin and cyclophosphamide versus weekly doxorubicin and daily oral cyclophosphamide plus granulocyte colony-stimulating factor as neoadjuvant therapy for inflammatory and locally advanced breast cancer: SWOG 0012. J Clin Oncol. 2011 Mar 10;29(8):1014-21. doi: 10.1200/JCO.2009.27.6543. Epub 2011 Jan 10.

Results Reference

background

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Phase II Trial of Neoadjuvant Metronomic Chemotherapy in Triple-Negative Breast Cancer

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