Patient-derived Xenograft (PDX) Modeling of Treatment Response for Triple Negative Breast Cancer

Triple Negative Breast Cancer Clinical Trial

Official title:

Patient-derived Xenograft (PDX) Modeling of Treatment Response for Triple Negative Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02247037
• Other study ID #: GCO 14-0686
• Status: Completed
• Start date: July 2014
• Est. completion date: January 22, 2019

Study information

• Verified date: July 2020
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will determine if patient-derived tumor xenograft (PDX) mouse models can serve as a reliable model for treatment response for individual patients with triple negative breast cancer. The collection of patient tumor tissue will also provide insight into the mechanisms of therapeutic resistance for those individuals. Ultimately, this study will enhance our understanding of the genomic basis for treatment response for triple negative cancer on an individual basis, while having the potential to suggest new therapeutic options for high-risk triple negative breast cancer patients with residual disease post neoadjuvant.

Description:

Triple negative breast cancer (TNBC) represents an aggressive, genomically heterogeneous, subtype of breast cancer with limited therapeutic options. Many patients with TNBC receive standard neoadjuvant chemotherapy (NAC) pre-operatively; response is directly correlated with long-term outcome. Patients with residual disease after NAC are at higher risk for recurrent or metastatic disease, but additional adjuvant therapies are not currently part of standard care. Personalized treatment for patients with TNBC requires an improved understanding of the genomic landscape of individual TN breast tumors, as well as improved predictive models of response to specific therapeutic agents. This pilot study will determine if patient-derived tumor xenograft (PDX) mouse models can serve as a reliable model for treatment response for individual patients with TNBC. The tumor tissue collected (paired pre-and post NAC) will also provide insight into mechanisms of therapeutic resistance for individual patients. This study will enhance our understanding of the genomic basis for treatment response for TNBC on an individual patient basis, and lead to potential new therapeutic options for high-risk TNBC patients with post-NAC residual disease.

Objectives:

1. To collect and bank tissue specimens from patients with operable triple negative breast cancer at: a) at time of diagnosis, prior to the start of neoadjuvant therapy and b) at time of definitive surgery, after the completion of neoadjuvant therapy.

2. To collect and bank tissue specimen for patients with advanced metastatic triple negative disease prior to start of any line therapy for metastatic disease.

3. To create patient-derived xenograft (PDX) mouse models utilizing specimens collected pre- and post- neoadjuvant treatment

4. To determine if response of PDX tumors to cytotoxic agents in the Champions Oncology Tumor GraftTM (COTG) assay correlates with responses observed in patients.

5. To perform genomic analyses of patient tumor specimens collected pre- and post neoadjuvant treatment to study mechanisms of drug resistance

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: January 22, 2019
• Est. primary completion date: January 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• a histological diagnosis of invasive triple negative breast cancer determined by standard immunohistochemical analysis.

• must be candidates for neoadjuvant chemotherapy according to standard of care guidelines or have evidence of metastatic disease.

• must agree to a biopsy for research purposes at time of diagnosis and to undergo surgery at the hospitals of the Mount Sinai Health System.

Patients with the following MAY be eligible:

• a histological diagnosis of ER and/or PR positive breast cancer with an overall receptor expression = 30% breast cancer determined by standard immunohistochemical analysis

Exclusion Criteria:

• concurrent disease or condition that would make the patient inappropriate for study participation,

• any serious medical or psychiatric disorder that would interfere with the subject's safety, or inability to provide informed consent.

• vulnerable populations will not be included.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Other:
• Chemotherapy
Patients are treated with neoadjuvant chemotherapy as according to the standard of care guidelines. Patients with metastatic disease are treated according to standard of care guidelines.

Locations

Country	Name	City	State
United States	Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	Champions Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient Tumor Response	Tumor response in patients will be categorized as: Progressive Disease, Static Response, Partial Response, Complete Response	Day 1
Secondary	Model Tumor Response	Tumor response in models will be categorized as: Progressive Disease, Static Response, Partial Response, Complete Response	Day 1