Genomic Signatures to Predict Treatment Response (AGO-Austria)

• ClinicalTrials.gov Identifier: NCT02032745
• Recruitment Status: Recruiting
• First Posted: January 10, 2014
• Last Update Posted: March 19, 2019
• Sponsor: Medical University of Graz
• Information provided by (Responsible Party): Peintinger Florentia, MD, Medical University of Graz

Study Description

Brief Summary:

A genomic test was developed to predict chemo-sensitivity to taxane-anthracycline-based chemotherapy as neoadjuvant treatment. The primary aim of this study is to prospectively evaluate the microarray-based, genomic test as a predictor of axillary lymph node response. Also, to determine whether the probability of achieving negative axillary nodes, is sufficiently high for patients whose breast cancer is predicted to be chemo-sensitive to support omitting axillary dissection.

Condition or disease
Breast Neoplasms

Study Design

• Study Type: Observational
• Estimated Enrollment: 277 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Prospective Validation of Genomic Signatures to Predict Treatment Response in the Axillary Nodes After Neoadjuvant Chemotherapy in Patients With HER2-negative Breast Cancer
• Study Start Date: August 2011
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: September 2020

Groups and Cohorts

Group/Cohort
Chemo-insensitive; Non-responders to chemotherapy (Probability for pathological negative nodal status)
Chemo-sensitive; Responders to chemotherapy (Probability for pathological negative nodal status)

Outcome Measures

Primary Outcome Measures :

1. Probability of achieving a negative axillary nodal status [ Time Frame: at time of surgery ]
   The overall rate of pathologic lymph node-negative status (pLN0) will be evaluated, including clinically lymph node-negative (cLN-) and lymph node-positive (cLN+) patients. For sample size calculation we will consider the rate of nodal conversion from clinically node-positive (cLN+) before treatment to pathologic node-negative (pLN0) after the completion of neoadjuvant chemotherapy. Patients who are clinically node positive (cLN+) will be evaluated for nodal response, i.e. conversion to pLN0 status. We assume that 30% of these patients will be predicted by the genomic predictor as responders (i.e. pLN0 status) after neoadjuvant chemotherapy, and that 70% of them will actually achieve pLN0 status. The study will be sized to have 80% power to detect observed response (pLN-negative) rates > 50% in cLN-positive patients after neoadjuvant chemotherapy at a 95% confidence level (one sided). Probability will be measured in percent.

Biospecimen Retention:   Samples With DNA

Breast cancer tissue

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Breast cancer patients with advanced HER 2 negative breast cancer

Criteria

Inclusion Criteria:

• Clinical status of lymph nodes must be available
• Sonographical status of lymph nodes must be available
• Patients must consent to documentation of cancer treatment
• Histologic diagnosis of invasive breast cancer, clinical stage T1-4, M0 (non-inflammatory T4c)
• Patients scheduled for neoadjuvant chemotherapy
• Treatment with a 3-weekly FEC or AC regimen (3-4 cycles) followed by 3-4 cycles of q3 weekly docetaxel or paclitaxel.
• Local HER2 status of tumor biopsy must be negative.

Exclusion Criteria:

• The patient has a prior history of invasive or metastatic breast cancer.
• The patient had prior excisional biopsy of the primary invasive breast cancer.
• The patient had prior ipsilateral sentinel axillary lymph node biopsy for breast cancer.
• The patient cannot safely or feasibly undergo biopsy of the primary tumor.
• The patient has a diagnosis of Stage IV (distant metastatic) breast cancer.
• The patient has proven HER2-positive breast cancer, defined as a pathology report of amplification of the gene or 3+ score for immunohistochemical staining.

Contacts and Locations

Contacts

Contact: Florentia Peintinger, M.D.; florentia.peintinger@medunigraz.at

Locations

Austria

Institute of Pathology, Med. Univ. Graz; Recruiting

Graz, Austria, 8036

Contact: Florentia Peintinger, M.D. florentia.peintinger@medunigraz.at

Sponsors and Collaborators

Medical University of Graz

More Information

Publications:

Hatzis C, Pusztai L, Valero V, Booser DJ, Esserman L, Lluch A, Vidaurre T, Holmes F, Souchon E, Wang H, Martin M, Cotrina J, Gomez H, Hubbard R, Chacón JI, Ferrer-Lozano J, Dyer R, Buxton M, Gong Y, Wu Y, Ibrahim N, Andreopoulou E, Ueno NT, Hunt K, Yang W, Nazario A, DeMichele A, O'Shaughnessy J, Hortobagyi GN, Symmans WF. A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer. JAMA. 2011 May 11;305(18):1873-81. doi: 10.1001/jama.2011.593.

Peintinger F, Anderson K, Mazouni C, Kuerer HM, Hatzis C, Lin F, Hortobagyi GN, Symmans WF, Pusztai L. Thirty-gene pharmacogenomic test correlates with residual cancer burden after preoperative chemotherapy for breast cancer. Clin Cancer Res. 2007 Jul 15;13(14):4078-82.

• Responsible Party: Peintinger Florentia, MD, Professor, Medical University of Graz
• ClinicalTrials.gov Identifier: NCT02032745
• Other Study ID Numbers: AGO-35; KLI 406 ( Other Grant/Funding Number: FWF )
• First Posted: January 10, 2014
• Last Update Posted: March 19, 2019
• Last Verified: March 2019

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases