Tumor Suppressor Status as a Predictor of Chemotherapy Response in Triple Negative Breast Cancer

• Conditions: Breast Cancer

• Registration Number: NCT01514565
• Lead Sponsor: Thomas Jefferson University

Brief Summary

This is a prospective observational study aimed to validate biomarkers that predict response.

Detailed Description

This is a prospective observational cohort study, with no control group and no direct experimental intervention, where the patient's pathological material will be used to examine the expression of molecular biomarkers believed to predict chemotherapy response. Patients with locally advanced triple negative breast cancer, who are candidates for neoadjuvant chemotherapy, will be enrolled in this clinical study. Patients will receive standard of care, FDA-approved and clinically validated chemotherapy regimens. The biopsy specimens taken during the diagnostic phase (pre-treatment specimen) will be used for specific biomarker evaluation. Data obtained from this pre-treatment phase will be compared with the surgical specimens (post-treatment phase) obtained after receiving neoadjuvant chemotherapy. The primary endpoint is to assess the ability of specific biomarkers to predict treatment response, and thus identify those patients who will achieve benefit from such treatment.

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2012-01-17
• Study First Submitted QC: 2012-01-20
• Study First Posted: 2012-01-23
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-17
• Last Update Posted: 2015-03-18
• Primary Completion: 2015-12
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 70

Inclusion Criteria

• Age > 18 years old
• Histologically-confirmed triple negative invasive breast carcinoma
• Any type of ductal or lobular invasive carcinoma
• Patients with or without BRCA-1 and BRCA-2 mutations are eligible to participate
• Life expectancy > 6 months
• Pre-, Peri- or Postmenopausal
• Clinical Stage T2-4, N0-3, M0 (Stage II-III)
• Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial
• Adequate hematologic, renal, and liver function and functional status that permit chemotherapy administration. However, these parameters will be evaluated by the treating physician, and decisions regarding eligibility for chemotherapy or surgery will be made on a case by case scenario.

Exclusion Criteria

• Prior history of and/or active therapy for invasive breast cancer (includes chemotherapy, radiation, hormonal therapy including AIs, tamoxifen, raloxifene, fulvestrant or any other antiestrogen/SERM)
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not to be registered. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are now considered to be at less than 30% risk for relapse (by their physician).
• Only ductal/lobular carcinoma in situ but not invasive component
• Any sort of confirmed metastatic disease (AJCC Stage IV at diagnosis)
• Any sort of active local radiation therapy (to the breast or the axilla), before the neoadjuvant chemotherapy
• Pregnant or lactating, in case this precludes the subject to receive chemotherapy.
• Impossibility to receive neoadjuvant chemotherapy due to significant medical comorbidities, allergies or performance status. This will be exclusively decided by the treating oncologists.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Histological status of retinoblastoma tumour suppressor (RB)	Nine weeks	The primary endpoint is to assess the impact of histological RB-status on pathological complete response (pCR). pCR is a well validated surrogate of chemotherapy sensitivity and allows the identification of a group of patients with excellent prognosis.

Secondary Outcome Measures

Name	Time	Method
Correlation of RB and other biomarkers	Nine weeks	1. Correlation between RB and PTEN tumor suppressor status and other biomarkers with pCR; 2. Correlation between RB-status, RB and PTEN status and other biomarkers with recurrence free survival (RFS) and overall survival (OS)
Determine the utility of an RB molecular test	Assessed within 1 year	Gene expression profiling of biopsy specimens to determine utility of an RB molecular test.

Trial Locations

Locations (1)

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States