Clinical trial NCT02247037: Patient-derived Xenograft (PDX) Modeling of Treatment Response for Triple Negative Breast Cancer
Official title: Patient-derived Xenograft (PDX) Modeling of Treatment Response for Triple Negative Breast Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Triple Negative Breast Cancer
Keywords: Triple Negative Breast Cancer
Patient Derived Xenograft
Neoadjuvant Chemotherapy
Therapeutic Resistance
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Champions Oncology
First posted: 2014-09-23
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Triple Negative Breast Cancer that are eligible for neoadjuvant chemotherapy or have evidence of metastatic disease will be pursued for this protocol.

Brief 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.

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Patient Tumor Response
timeFrame: Day 1
Secondary outcomes:
measure: Model Tumor Response
timeFrame: Day 1
Other outcomes:
Locations:
city: New York
country: United States
facility: Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai
state: New York
Study officials:
affiliation: Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai
name: Hanna Yoko Irie, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai
name: Elisa Port, MD
role: PRINCIPAL_INVESTIGATOR
References: