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

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

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

Study Overview

• Status: Unknown
• Conditions: Breast Cancer

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 Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
      • Contact: Agnieszka Witkiewicz, MD; Phone Number: 215-955-3778; Email: Agnieszka.Witkiewicz@jefferson.edu
      • Contact: Gordon Schwartz, MD; Phone Number: 215-955-6999; Email: Gordon.Schwartz@jefferson.edu
      • Sub-Investigator: Matias Valsecchi, MD
      • Sub-Investigator: A. Kathleen McClendon, PhD
      • Sub-Investigator: Adam Berger, MD
      • Sub-Investigator: Sunny Lee, MD
      • Sub-Investigator: Barbara Cavanaugh, MD
      • Sub-Investigator: Frederick Fellin, MD
      • Sub-Investigator: Allison Zibelli, MD
      • Sub-Investigator: Tiffany Avery, MD
      • Sub-Investigator: Rebecca Jaslow, MD
      • Sub-Investigator: Erik Knudsen, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

A maximum of 70 eligible patients will be enrolled. Accrual is expected to be completed in 18-24 months. All patients must have histologically confirmed triple negative breast cancer and be eligible to receive neoadjuvant chemotherapy.

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histological status of retinoblastoma tumour suppressor (RB)	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.	Nine weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Investigators: Principal Investigator: Agnieszka Witkiewicz, MD, Thomas Jefferson University; Principal Investigator: Gordon Schwartz, MD, Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ANTICIPATED): December 1, 2015
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: January 17, 2012
• First Submitted That Met QC Criteria: January 20, 2012
• First Posted (ESTIMATE): January 23, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 18, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Chemotherapy; Neoadjuvant; PTEN; Triple negative Breast Cancer; RB
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: 11D-574