Neoadjuvant Platinum-based Chemoradiation Therapy for Locally Advanced Triple Negative Breast Cancer

Breast Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01167192
• Other study ID #: 201310089
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 14, 2010
• Last updated: December 17, 2015
• Start date: February 2011
• Est. completion date: October 2017

Study information

• Verified date: December 2015
• 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 platinum-based chemotherapy, when given with radiation therapy prior to surgery, is effective in improving response to treatment in triple negative breast cancer patients.

Description:

The purpose of this study is to determine whether platinum-based chemotherapy (either cisplatin or carboplatin), when given with radiation therapy prior to surgery, is effective in improving response to treatment in triple negative breast cancer patients. This treatment is being studied in this type of breast cancer because it does not respond well to commonly used treatments such as tamoxifen or herceptin.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 53
• Est. completion date: October 2017
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient must be > or = 18 years of age

• Patient must be female

• Patient must have primary invasive ductal breast adenocarcinoma that either:

1. is newly diagnosed, without previous systemic treatment OR

2. has failed to respond to < or = 4 cycles of neoadjuvant anthracycline based therapy as assessed by clinical exam or imaging studies (mammogram, ultrasound or breast MRI).

• Patient's tumor must be classified as clinically stage T2, T3, or T4 with any N (NX, N0, N1, N2, or N3) prior to any neoadjuvant treatment.

• Patient must have an ECOG Performance Status of < or = 1.

• Patient must have adequate organ function defined as:

1. Renal Function:

1. CrCl = 60 ml/min for patients receiving cisplatin

2. CrCl = 30 ml/min for patients receiving carboplatin.

2. Liver Function:

1. ALT, AST, ALK Phos < or = 1.5 x upper limit of institutional normal.

2. Bilirubin < or = 1.5 x upper limit of institutional normal.

3. Normal left ventricular function (LVEF > 50%) by MUGA or ECHO.

4. Hematologic:

1. Absolute Neutrophil Count > or = 1500/mcl

2. Platelets > or = 100,000/mcl

3. Hemoglobin > or = 8.0 g/dl

• Patient must be able and willing to sign informed consent document.

Exclusion Criteria:

• Patient must not have evidence of distant metastasis present by CT, bone scan, or PET-CT. 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 at the discretion of the treating physician.

• Patients having received neoadjuvant anthracycline based therapy must undergo restaging to exclude distant metastases prior to enrollment.

• Patient must not have had any 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.

• Patient's tumor must not express the following biomarkers or must have Allred score < 4 for: estrogen receptor, progesterone receptor, and is not Her2/neu amplified.

• Women of child bearing potential may not be currently pregnant or breastfeeding at time of registration and must agree to use adequate contraception.

• Patient must have > or = grade 2 peripheral neuropathy.

• Patient must have a known hearing impairment (hearing loss or severe tinnitus). Hearing test will be performed at the discretion of the treating physician.

• Patient must not have been previously treated with cisplatin or carboplatin for any condition.

Study Design

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Cisplatin

• Carboplatin

Radiation:
• Radiation therapy

Procedure:
• Mastectomy (recommended but not mandatory)

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 (4)

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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine whether radiation combined with platinum improves the clinical response rate in patients with locally advanced TN tumors		Prior to surgery (within 4 weeks)	No
Primary	Obtain preliminary information on the relationship between tumor response in patients with locally advanced triple negative breast cancer treated with platinum-based chemoradiation correlates with deficiencies in DNA repair mechanisms		Prior to surgery (within 4 weeks)	No
Secondary	Determine the effect of neoadjuvant chemoradiation on tumor response to therapy		Prior to surgery (within 4 weeks)	No
Secondary	Time to disease progression		5 years	No
Secondary	Surgical complications		30 days post surgery	No
Secondary	Effect of neoadjuvant chemoradiation therapy in disseminated cancer cells in the bone marrow and correlation to tumor response		At time of IVAD placement, at time of surgery, and 12-15 months after initial registration	No
Secondary	Overall survival		5 years	No
Secondary	Medical toxicities with platinum-based chemoradiation		30 days post the last bone marrow biopsy	Yes
Secondary	Develop of animal models of triple negative breast cancers		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