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

Breast Cancer Clinical Trial

Official title:

Effect of Neoadjuvant Cisplatin Based Chemoradiation Therapy for Locally Advanced Triple Negative Breast Cancer: Clinical Outcome and Correlation to Biological Parameters

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00603408
• Other study ID #: 07-0913
• Status: Terminated
• Phase: Phase 2
• First received: December 28, 2007
• Last updated: July 22, 2013
• Start date: December 2007
• Est. completion date: December 2009

Study information

• Verified date: July 2013
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

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/m2 (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/m2 (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/m2 (cycle 3)

Week 10: Chemo Day 1:Cisplatin 75mg/m2 (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/m2 & Cyclophosphamide: 600mg/m2, every 2 weeks for 4 cycles

Week 21 - 29: Recommended (physician discretion) Adjuvant Chemo Paclitaxel: 175mg/m2 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Cisplatin

Radiation:
• Radiation Therapy

Procedure:
• Mastectomy
(RECOMMENDED BUT NOT REQUIRED)

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (17)

Bollet MA, Sigal-Zafrani B, Gambotti L, Extra JM, Meunier M, Nos C, Dendale R, Campana F, Kirova YM, Diéras 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. Epub 2006 Aug 8. — View Citation

Braun S, Naume B. Circulating and disseminated tumor cells. J Clin Oncol. 2005 Mar 10;23(8):1623-6. Review. — View Citation

Braun S, Pantel K, Müller P, Janni W, Hepp F, Kentenich CR, Gastroph S, Wischnik A, Dimpfl T, Kindermann G, Riethmüller 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. Erratum in: N Engl J Med 2000 Jul 27;343(4):308. — View 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. — View Citation

Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007 Mar;8(3):235-44. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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.

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. — View Citation

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. Erratum in: N Engl J Med 1999 Aug 26;341(9):708. — View Citation

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. — View Citation

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. — View Citation

Rowinsky EK, Donehower RC. Paclitaxel (taxol). N Engl J Med. 1995 Apr 13;332(15):1004-14. Review. Erratum in: N Engl J Med 1995 Jul 6;333(1):75. — View Citation

Sørlie 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, Lønning PE, Børresen-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. — View Citation

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. Epub 2006 Oct 2. — View Citation

Turner NC, Reis-Filho JS. Basal-like breast cancer and the BRCA1 phenotype. Oncogene. 2006 Sep 25;25(43):5846-53. Review. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical response rate in patients with locally advanced TN tumors who received radiation combined with cisplatin	Obtain preliminary information on the relationship between tumor response in patients with locally advanced triple negative breast cancer treated with cisplatin based chemoradiation correlates with deficiencies in DNA repair mechanisms.	5 years	No
Secondary	Time to disease progression		5 years	No
Secondary	Overall survival		5 years	No
Secondary	Surgical complications of cisplatin based chemoradiation		30 days post surgery	Yes
Secondary	Medical toxicities with cisplatin based chemoradiation		30 days post surgery	Yes
Secondary	Effect of neoadjuvant chemoradiation therapy in disseminated cancer cells in the bone marrow and correlation to tumor response		5 years	No
Secondary	Develop animal models of triple negative breast cancers		5 years	No
Secondary	Provide samples for the development of the FNA assay		At time of IVAD placement and at time of surgery	No

External Links

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