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Personalized Patient Derived Xenograft (pPDX) Modeling to Test Drug Response in Matching Host

Personalized Patient Derived Xenograft (pPDX) Modeling to Test Drug Response in Matching Host

Recruiting
18 years and older
All
Phase N/A

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Overview

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

Description

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.

Eligibility

Inclusion Criteria:

  1. Age > 18 years.
  2. 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:

    • Stage IV (metastatic) disease that has not been treated with systemic therapy in the metastatic setting or
    • Stage I to III (non-metastatic) with residual mass by clinical exam and/or breast imaging following anthracycline + taxane-containing neoadjuvant chemotherapy

OR

             (II) Histologically-confirmed Stage IV colorectal cancer treated with ≤ 1 line of
             systemic therapy in the metastatic setting, either:
               -  Undergoing surgical resection of liver metastases or
               -  With metastatic lesions amenable to biopsy
             OR
             (III) Histologically-confirmed advanced High Grade Serous Ovarian Cancer, either:
               -  Recurrent disease with a life expectancy of at least 12 months or
               -  Stage III or IV with residual disease following neoadjuvant chemotherapy, or at
                  risk of high recurrence
             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
          3. Disease amenable to biopsy or surgery for tissue procurement
          4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
          5. Willingness and ability of patient to provide signed voluntary informed consent.
        Exclusion Criteria:
          1. Clinically significant hepatic, renal, cardiac or other organ dysfunction likely to
             limit participation in clinical trials.
          2. Known brain metastasis
          3. Any condition that could interfere with a patient's ability to provide informed
             consent such as dementia or severe cognitive impairment.
          4. Any contraindication to undergoing a biopsy procedure.

Study details
    Colorectal Neoplasms
    Colorectal Cancer
    Breast Cancer
    Breast Neoplasms
    Ovarian Cancer
    Ovarian Neoplasm

NCT02732860

University Health Network, Toronto

26 January 2024

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