Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Needle Core Biopsies

Katarzyna J Jerzak, MD MSc FRCPC

Hon S Leong

The investigators propose to use clinically validated patient avatar technology ("PDXovo") that can test multiple drugs against patients' cancers to identify the most promising systemic therapy for each individual.

The primary goal of this feasibility study is to determine the percentage of patients for whom PDXs are successfully generated within 7-10 days. This will give the investigators an indication of the success rate for providing patients with actionable information if this PDX technology were to be implemented in the clinic. Since the PDXs will also receive the same drug as the patient, there is an opportunity to assess the agreement between the clinical response and the PDX response.

As a secondary goal, the response of PDXs will be compared to the patient's response to systemic therapy, as measured using the objective response rate at 12 weeks +/- 4 weeks (ORR, measured using RECIST 1.1 criteria).

Integrated Patient Avatars for Guiding Systemic Therapy Treatments in Metastatic Breast Cancer Patients

Integrated Patient Avatars for Guiding Systemic Therapy Treatments: "Intuition-Free" Decisions in Metastatic Breast Cancer Patients

perform a feasibility study to determine the tumor take rate(s) in PDXs generated from needle core biopsies collected from metastatic breast cancer patients

The response of PDXs will be compared to the patient's response to systemic therapy, as measured using the objective response rate.

AFP Innovation Fund

Sunnybrook Health Sciences Centre

Medical Oncologist & Associate Scientist

Symptoms and General Pathology

Triple Negative Breast Neoplasms

Neoplasm Metastasis

Hematinics

All Drugs and Chemicals

Antineoplastic Agents

Liver Extracts

Taxane

No investigational products will be administered to subjects as part of this translational research study. Needle core biopsies will be done to collect tumor samples.

A taxane-based regimen will be administered as per the standard of care at each treating institution. Tissue samples from primary tumors will be collected and banked before the start of chemotherapy, after chemotherapy and at the time of surgery. Additionally, blood samples will be drawn before treatment initiation (baseline) and at different time points during treatment and stored in the tissue biobank.

Needle core biopsies

No investigational products will be administered to subjects as part of this translational research study. Needle core biopsies will be done to collect metastasis tumor samples.

Chemotherapy will be administered as per the standard of care at each treating institution. Tissue samples from metastatic tumors lesions will be collected and banked before the start of chemotherapy and at the time of progression. Additionally, blood samples will be drawn before treatment initiation (baseline) and at different time points during treatment and stored in the tissue biobank.

Needle core biopsies of metastatic lesion

Mark Basik, MD

This is a multicenter translational study to understand therapeutic resistance in patients undergoing standard chemotherapy for triple negative breast cancer.

In the neoadjuvant setting, biopsy tissue samples from primary tumor will be collected and banked before the start of chemotherapy and after the completion of the treatment (post-chemotherapy and at the time of surgery). In the metastatic setting, tissue samples from metastatic lesions will be collected and banked before the start of chemotherapy and at the time of tumor progression. Additionally, blood samples will be drawn before treatment initiation (baseline) and at different time points during treatment. All samples will be stored in the Biological Resource Repository.

Mechanisms of resistance have been studied for many years in various experimental models. However, many drugs that are highly effective in experimental models at overcoming resistance have been either ineffective or marginally active in preliminary clinical studies. Thus after decades of study, most reviews of anti-cancer drug resistance still focus largely on experimental models, which may not reflect resistance in humans. However, recent studies have demonstrated that clinical resistance occurs in primary and metastatic tumors that may have undergone significant molecular evolution due to treatment effects and the selection of clones as recently shown in breast cancer.

Triple negative breast cancer is a subtype that carries a poor prognosis and a high incidence of early metastatic recurrence. Furthermore, no target therapy is efficacious up to now in this subtype. Thus, identification of mechanisms of resistance to available therapies and prediction of tumoral response to various treatments could help in the management of patients affected by this particularly aggressive type of breast cancer.

The goals of this study are two-fold. First, to build a biobank of blood and tissue specimens, prior to starting chemotherapy and at a determined time-point (surgery or progression of disease), from patients undergoing the chemotherapeutic treatments in the neoadjuvant and metastatic settings. Second, to use cutting-edge molecular techniques available in several Quebec research centers, to carefully compare these pre and post treatment samples to identify "molecular factors of resistance". The discovery of these factors will help oncologists in triaging patients to receive the most beneficial therapy by recognizing when not to give particular treatment and will be essential for reducing the potential for harmful side effects and for avoiding the extremely high cost of modern treatments when they can be predicted to be ineffective.

Tumor samples from the primary breast tumor or metastatic lesions will be obtained by needle core biopsy. In the neoadjuvant setting, samples will be also collected at the time of surgery. To obtain sufficient material for tissue banking, four needle core biopsies will be removed from the same neoplastic lesion. Two of the biospecimens will be snap frozen for phosphoprotein preservation, one will be placed in RNAlater for nucleic acid preservation and the other one will be placed in formalin for FFPE. Additionally, blood samples will be collected at different time points during treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Integrated Patient Avatars for Guiding Systemic Therapy Treatments in Metastatic Breast Cancer Patients	NCT04608357	Breast Cancer Breast Neoplasm... Metastatic Brea... Cancer, Breast	Needle Core Bio...	18 Years -	Sunnybrook Health Sciences Centre
Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients	NCT01276899	Triple Negative...	Needle core bio... Needle core bio...	18 Years -	Jewish General Hospital
Study to Identify Molecular Mechanisms of Clinical Resistance to Chemotherapy in Triple Negative Breast Cancer Patients	NCT01276899	Triple Negative...	Needle core bio... Needle core bio...	18 Years -	Jewish General Hospital
Integrated Patient Avatars for Guiding Systemic Therapy Treatments in Metastatic Breast Cancer Patients	NCT04608357	Breast Cancer Breast Neoplasm... Metastatic Brea... Cancer, Breast	Needle Core Bio...	18 Years -	Sunnybrook Health Sciences Centre

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