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By obtaining clinical specimens from participants with triple negative breast cancer (TNBC), colorectal cancer (CRC), high grade serous ovarian cancer (HGSOC), and other select tumor types to establish and profile as freshly implanted tumors in mice, the aim of this study is to identify agents with predicted activity in the host patient while also potentially providing them with personalized cancer treatment options
Personalized patient-derived xenografts (pPDX) are increasingly used as tools for drug development in pre-clinical settings, and have been shown to recapitulate the histology and behavior of the cancers from which they are derived. Although, they have been commonly used productively as pre-clinical disease models to study disease biology and drug response, they have not been used prospectively to inform clinical management. pPDX have been employed to inform clinical decision-making in small studies, which have shown high concordance between individual pPDX and patient responses to therapy. While encouraging, the role of this approach in breast, colorectal, ovarian, and other cancer populations and in the context of genomic drug matching strategies remains undefined. This has created an opportunity to evaluate the utility of pPDX as clinical predictors to direct the use of chemo- and targeted therapies in combination with comprehensive genomic and epigenetic analysis for patients with TNBC, CRC, HGSOC and other selected tumor types.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Triple Negative Breast Cancer | Triple negative breast cancer patients with residual invasive disease following neoadjuvant chemotherapy (n= up to 15) or with newly diagnosed metastatic disease (n=up to 30). After the screening procedures confirms patient eligibility:
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| Colorectal Cancer | Colorectal cancer patients with metastatic disease undergoing resection of liver metastases, or with lesions amenable to biopsy (n=up to 15). After the screening procedures confirms patient eligibility:
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| High Grade Serous Ovarian Cancer | High grade serous ovarian cancer patients with recurrent disease with a life expectancy of at least 12 months (n=up to 15), or Stage III or IV with residual disease following neoadjuvant chemotherapy, or at risk of high recurrence (n=up to 15). After the screening procedures confirms patient eligibility:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures | Other | Molecular profiling of host tumour sample and pPDX will be performed and analyzed by an expert panel. In vitro organoid culture generation may also be performed if sufficient fresh tissue is available. Matched treatment recommendation based on profiling and in vivo pPDX drug testing results will be made, if available. This recommendation will be communicated to the primary oncologist. |
| Measure | Description | Time Frame |
|---|---|---|
| Measure of drug sensitive pPDX to a panel of drugs as a predictor of clinical response in matched host | Sensitivity measured by tumor growth inhibition (>80%) or objective tumor response (regression) as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. | up to 5 years |
| Rate of results reporting | up to 5 years | |
| Rate of pPDX engraftment | up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of actionable alterations identified in clinical and pPDX samples | Genomic alterations identified using the Ion Proton System for Next-Generation Sequencing (NGS). | up to 5 years |
| Number of patients with molecular abnormalities in pPDX as identified via NGS eliciting clinical responses while receiving matched treatments. |
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Inclusion Criteria:
Age > 18 years.
Patient diagnosis must be categorized as either (I) OR (II) OR (III) OR (IV):
(I) Histologically confirmed Triple Negative Breast Cancer by Institutional and American Society of Clinical Oncology (ASCO)/Cancer of American Pathologists (CAP) guidelines, either:
OR
(II) Histologically-confirmed Stage IV colorectal cancer treated with ≤ 1 line of systemic therapy in the metastatic setting, either:
OR
(III) Histologically-confirmed advanced High Grade Serous Ovarian Cancer, either:
OR
(IV) Histologically confirmed solid tumor not meeting criteria for (I), (II) or (III) above, for which evaluation of investigational therapies is of particular interest or where clinical need exists, at the discretion of the PI
Disease amenable to biopsy or surgery for tissue procurement
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Willingness and ability of patient to provide signed voluntary informed consent.
Exclusion Criteria:
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Patients with TNBC, CRC, HGSOC, or selected other tumour types, referred to, or being treated at Princess Margaret Cancer Centre.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| David Cescon, MD | Contact | 416-946-2245 | Dave.Cescon@uhn.ca |
| Name | Affiliation | Role |
|---|---|---|
| David Cescon, MD | Princess Margaret Cancer Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Princess Margaret Cancer Centre | Recruiting | Toronto | Ontario | M5G 2M9 | Canada |
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Whole Blood, formalin fixed paraffin embedded blocks, fresh tumor tissue, malignant effusion or ascites (if no tumor tissue available), archival tissue (if not enrolled in molecular profiling studies IMPACT/OCTANE)
| Other tumor types | Other selected tumor types at the discretion of the PI (n= up to 30) After the screening procedures confirms patient eligibility:
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Overall accuracy of clinical responses as assessed by RECIST criteria in patient tumor. |
| up to 5 years |
| Correlation between pPDX and organoid drug sensitivities | up to 5 years |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D001943 | Breast Neoplasms |
| D010051 | Ovarian Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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