Effect of Chemotherapy and Radiation Prior to Surgery for Triple Negative Breast Cancer
8. juli 2016 opdateret af: Washington University School of Medicine
Effect of Neoadjuvant Cisplatin Based Chemoradiation Therapy for Locally Advanced Triple Negative Breast Cancer: Clinical Outcome and Correlation to Biological Parameters
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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
5
Fase
- Fase 2
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Missouri
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St. Louis, Missouri, Forenede Stater, 63110
- Washington University School of Medicine
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Kvinde
Beskrivelse
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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: 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 |
Andre navne:
(RECOMMENDED BUT NOT REQUIRED)
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Overall Response
Tidsramme: At the time of surgery (week 13)
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At the time of surgery (week 13)
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Time to Disease Progression
Tidsramme: Until study was terminated (23.5 months)
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Time to disease progression: time from registration until objective tumor progression; does not include deaths
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Until study was terminated (23.5 months)
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Overall Survival Rate (OS)
Tidsramme: Until study was terminated (23.5 months)
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OS = Time from registration until death from any cause
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Until study was terminated (23.5 months)
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Number of Participants With Surgical Complications
Tidsramme: 30 days post surgery (week 17-18)
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30 days post surgery (week 17-18)
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Number of Participants With Medical Toxicities
Tidsramme: 30 days post surgery (week 17-18)
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The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.
All detailed information regarding serious and other adverse events are listed in the Adverse Event module of these results.
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30 days post surgery (week 17-18)
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Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and Correlation to Tumor Response
Tidsramme: 5 years
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5 years
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Develop Animal Models of Triple Negative Breast Cancers
Tidsramme: 5 years
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5 years
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Provide Samples for the Development of the FNA Assay
Tidsramme: At time of IVAD placement and at time of surgery
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At time of IVAD placement and at time of surgery
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Efterforskere
- Ledende efterforsker: Rebecca Aft, MD, PhD, Washington University School of Medicine
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Formenti SC, Volm M, Skinner KA, Spicer D, Cohen D, Perez E, Bettini AC, Groshen S, Gee C, Florentine B, Press M, Danenberg P, Muggia F. Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicin-based chemotherapy in locally advanced breast cancer: a phase I/II trial. J Clin Oncol. 2003 Mar 1;21(5):864-70. doi: 10.1200/JCO.2003.06.132.
- 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.
- 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.
- Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999 Apr 15;340(15):1154-61. doi: 10.1056/NEJM199904153401503. Erratum In: N Engl J Med 1999 Aug 26;341(9):708.
- Rowinsky EK, Donehower RC. Paclitaxel (taxol). N Engl J Med. 1995 Apr 13;332(15):1004-14. doi: 10.1056/NEJM199504133321507. No abstract available. Erratum In: N Engl J Med 1995 Jul 6;333(1):75.
- 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.
- Diel IJ, Cote RJ. Bone marrow and lymph node assessment for minimal residual disease in patients with breast cancer. Cancer Treat Rev. 2000 Feb;26(1):53-65. doi: 10.1053/ctrv.1999.0150.
- 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. Erratum In: N Engl J Med 2000 Jul 27;343(4):308.
- Braun S, Naume B. Circulating and disseminated tumor cells. J Clin Oncol. 2005 Mar 10;23(8):1623-6. doi: 10.1200/JCO.2005.10.073. No abstract available.
- 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.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. december 2007
Primær færdiggørelse (Faktiske)
1. december 2009
Studieafslutning (Faktiske)
1. december 2009
Datoer for studieregistrering
Først indsendt
28. december 2007
Først indsendt, der opfyldte QC-kriterier
28. januar 2008
Først opslået (Skøn)
29. januar 2008
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
19. august 2016
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
8. juli 2016
Sidst verificeret
1. juli 2016
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 07-0913
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .