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

NCT00603408 | Terminated Phase 2 Results

• 1 other identifier: 07-0913
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Breast Cancer; Locally Advanced; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Overall Response

  * Complete response: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level * Partial response: at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD * Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started, * Progressive disease: at least a 20% increase in the sum of the LD of the target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, appearance of one more new lesions, or unequivocal progression of existing non-target lesions.

  At the time of surgery (week 13)

Secondary Outcomes (7)

• Time to Disease Progression

  Until study was terminated (23.5 months)

• Overall Survival Rate (OS)

  Until study was terminated (23.5 months)

• Number of Participants With Surgical Complications

  30 days post surgery (week 17-18)

• Number of Participants With Medical Toxicities

  30 days post surgery (week 17-18)

• Effect of Neoadjuvant Chemoradiation Therapy in Disseminated Cancer Cells in the Bone Marrow and Correlation to Tumor Response

  5 years

Study Arms (1)

Cisplatin + Radiation + Recommended Surgery

EXPERIMENTAL

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

Drug: Cisplatin; Radiation: Radiation Therapy; Procedure: Mastectomy

Interventions

Cisplatin DRUG

Also known as: cisplatinum

Cisplatin + Radiation + Recommended Surgery

Radiation Therapy RADIATION

Cisplatin + Radiation + Recommended Surgery

Mastectomy PROCEDURE

(RECOMMENDED BUT NOT REQUIRED)

Cisplatin + Radiation + Recommended Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (17)

• 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.

  PMID: 17329194 BACKGROUND

• 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.

  PMID: 11553815 BACKGROUND

• 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.

  PMID: 16757721 BACKGROUND

• 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.

  PMID: 16998499 BACKGROUND

• 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.

  PMID: 17016441 BACKGROUND

• 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.

  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.

  PMID: 16893641 BACKGROUND

• 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.

  PMID: 12610186 BACKGROUND

• 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.

  PMID: 10334517 BACKGROUND

• 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.

  PMID: 10202164 BACKGROUND

• 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.

  PMID: 10202166 BACKGROUND

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

  PMID: 7885406 BACKGROUND

• 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.

  PMID: 7692001 BACKGROUND

• 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.

  PMID: 10660491 BACKGROUND

• 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.

  PMID: 10684910 BACKGROUND

• 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.

  PMID: 15755968 BACKGROUND

• 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.

  PMID: 15666325 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cisplatin; Radiotherapy; Mastectomy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics; Surgical Procedures, Operative

Results Point of Contact

• Title: Rebecca Aft, M.D., Ph.D.
• Organization: Washington University School of Medicine

aftr@wudosis.wustl.edu

314-747-0063

Study Officials

• Rebecca Aft, MD, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2007
• First Posted: January 29, 2008
• Study Start: December 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: August 19, 2016
• Results First Posted: August 19, 2016

Record last verified: 2016-07

Locations

US (1)