Effect of Chemotherapy and Radiation Prior to Surgery for Triple Negative Breast Cancer

NCT ID: NCT00603408

Last Updated: 2016-08-19

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-12-31

Study Completion Date

2009-12-31

Brief Summary

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The purpose of this study is to determine whether Cisplatin when given with radiation therapy prior to surgery is effective in improving response to treatment in breast cancer patients. Tumor, blood and bone marrow samples will be collected in this study and will also help researchers determine if cisplatin is able to change tumor DNA so it cannot multiply itself and create more tumor cells, and cause the tumor cells to die.

Detailed Description

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After Diagnosis: Clinical Stage IIB, III Breast Cancer, Triple Negative

Week 0: Port-A-Cath placement Tumor biopsy (Core and FNA) Blood collection Bone marrow aspiration Sentinel Lymph node biopsy, if axillary US negative

Week 1: Chemo \& Radiation Day 1: Radiation Therapy, Cisplatin 75mg/m\^2 (cycle 1) Days 2-5: Radiation Therapy

Week 2: Radiation Day 1-5: Radiation Therapy

Week 3: Radiation Days 1-5: Radiation Therapy

Week 4: Chemo \& Radiation Day 1: Radiation Therapy, Cisplatin 75mg/m\^2 (cycle 2) Days 2-5: Radiation Therapy

Week 5: Radiation Days 1-5: Radiation Therapy

Week 6: Radiation Days 1-5: Radiation Therapy

Week 7: Chemo Day 1: Cisplatin 75mg/m\^2 (cycle 3)

Week 10: Chemo Day 1:Cisplatin 75mg/m\^2 (cycle 4)

Week 13: Surgery Mastectomy with/without axillary lymph node dissection Tumor biopsy (Core and FNA) Blood collection Bone marrow aspiration

Week 15 - 21: Recommended (physician discretion) Adjuvant Chemo Dose dense Doxorubicin: 60mg/m\^2 \& Cyclophosphamide: 600mg/m\^2, every 2 weeks for 4 cycles

Week 21 - 29: Recommended (physician discretion) Adjuvant Chemo Paclitaxel: 175mg/m\^2 every 2 weeks for 4 cycles

Week 52 IVAD Removal, Bone marrow aspiration

Follow-Up (up to 5 years) Q 3 months for year 1 Q 6 months for year 2-3 Q 1 year for years 4-5

Conditions

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Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cisplatin + Radiation + Recommended Surgery

Cisplatin 75 mg/m\^2 IV Day 1 Week 1, Day 1 Week 2, Day 1 Week 7, Day 1 Week 10

Radiation = Total dose to breast or chest wall will be 50-60 Gy in 1.8-2.0 Gy daily fractions. Internal mammary nodes, supraclavicular fossa nodes and axillary nodal basins will receive 45-50 Gy over 5-6 weeks.

Surgery (recommended) mastectomy with/without axillary lymph node dissection

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Radiation Therapy

Intervention Type RADIATION

Mastectomy

Intervention Type PROCEDURE

(RECOMMENDED BUT NOT REQUIRED)

Interventions

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Cisplatin

Intervention Type DRUG

Radiation Therapy

Intervention Type RADIATION

Mastectomy

(RECOMMENDED BUT NOT REQUIRED)

Intervention Type PROCEDURE

Other Intervention Names

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cisplatinum

Eligibility Criteria

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Inclusion Criteria

* Patients must be \>= 18 years of age
* Patients must be newly diagnosed with primary invasive ductal breast adenocarcinoma.
* Tumor classified as clinically stage T2, T3 or T4 with any N (NX, N1, N2, or N3).
* Tumor does not express the following biomarkers: estrogen receptor, progesterone receptor, Her2/neu
* Adequate organ function defined as:

* Serum Creatinine \<= 1.5 x upper limit of institutional normal.
* ALT, AST, ALK Phos \<= 1.5 x upper limit of institutional normal.
* Bilirubin \<= 1.5 x upper limit of institutional normal.
* Normal left ventricular function (LVEF \> 50%) by MUGA or ECHO.

Exclusion Criteria

* No evidence of distant metastasis present by CT, Bone scan, or physical exam. If the bone scan or CT scans demonstrate indeterminate lesions, the nature of these lesions should be further clarified by additional testing such as PET or MRI.
* No prior malignancies with the exception of curatively treated basal or squamous carcinoma of the skin or history of previous malignancies, treated with at least greater than 5 years disease free survival.
* Women of child bearing potential may not be currently pregnant or breastfeeding at time of registration and must agree to use adequate contraception.
* Karnofsky Performance Status of \<= 70.
* Patients with known history neural deficiencies (e.g. peripheral neuropathy).
* Patients with a known hearing impairment (hearing loss or severe tinnitus).
* Male patients
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rebecca Aft, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007 Mar;8(3):235-44. doi: 10.1016/S1470-2045(07)70074-8.

Reference Type BACKGROUND
PMID: 17329194 (View on PubMed)

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.

Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 16757721 (View on PubMed)

Turner NC, Reis-Filho JS. Basal-like breast cancer and the BRCA1 phenotype. Oncogene. 2006 Sep 25;25(43):5846-53. doi: 10.1038/sj.onc.1209876.

Reference Type BACKGROUND
PMID: 16998499 (View on PubMed)

Turner NC, Reis-Filho JS, Russell AM, Springall RJ, Ryder K, Steele D, Savage K, Gillett CE, Schmitt FC, Ashworth A, Tutt AN. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene. 2007 Mar 29;26(14):2126-32. doi: 10.1038/sj.onc.1210014. Epub 2006 Oct 2.

Reference Type BACKGROUND
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Garber, J., Richardson, A., Harris, L., Miron, A., Silver, D., Golshan, M., Ryan, P., Ganesan, S., Wang, Z., Clarke, K., Inglehart, J., and Winer, E. Neoadjuvant cisplatin in triple negative breast cancer. SABCS, 2006.

Reference Type BACKGROUND

Bollet MA, Sigal-Zafrani B, Gambotti L, Extra JM, Meunier M, Nos C, Dendale R, Campana F, Kirova YM, Dieras V, Fourquet A; Institut Curie Breast Cancer Study Group. Pathological response to preoperative concurrent chemo-radiotherapy for breast cancer: results of a phase II study. Eur J Cancer. 2006 Sep;42(14):2286-95. doi: 10.1016/j.ejca.2006.03.026. Epub 2006 Aug 8.

Reference Type BACKGROUND
PMID: 16893641 (View on PubMed)

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Reference Type BACKGROUND
PMID: 12610186 (View on PubMed)

Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. doi: 10.1200/JCO.1999.17.5.1339.

Reference Type BACKGROUND
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Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. doi: 10.1056/NEJM199904153401501.

Reference Type BACKGROUND
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Reference Type BACKGROUND
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Rowinsky EK, Donehower RC. Paclitaxel (taxol). N Engl J Med. 1995 Apr 13;332(15):1004-14. doi: 10.1056/NEJM199504133321507. No abstract available.

Reference Type BACKGROUND
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Rowinsky EK, Chaudhry V, Forastiere AA, Sartorius SE, Ettinger DS, Grochow LB, Lubejko BG, Cornblath DR, Donehower RC. Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting. J Clin Oncol. 1993 Oct;11(10):2010-20. doi: 10.1200/JCO.1993.11.10.2010.

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Reference Type BACKGROUND
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Braun S, Pantel K, Muller P, Janni W, Hepp F, Kentenich CR, Gastroph S, Wischnik A, Dimpfl T, Kindermann G, Riethmuller G, Schlimok G. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med. 2000 Feb 24;342(8):525-33. doi: 10.1056/NEJM200002243420801.

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Reference Type BACKGROUND
PMID: 15755968 (View on PubMed)

Janni W, Rack B, Schindlbeck C, Strobl B, Rjosk D, Braun S, Sommer H, Pantel K, Gerber B, Friese K. The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence. Cancer. 2005 Mar 1;103(5):884-91. doi: 10.1002/cncr.20834.

Reference Type BACKGROUND
PMID: 15666325 (View on PubMed)

Related Links

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http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

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07-0913

Identifier Type: -

Identifier Source: org_study_id

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