Patient case: 73-year-old female with breast cancer; genetic feature: CDKN2A

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

Summary: By obtaining clinical specimens from participants with triple negative breast cancer (TNBC), colorectal cancer (CRC) 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

Detailed 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 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 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):
  (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 solid tumor not meeting criteria for (I) or (II) 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.

Relevance to patient case: not relevant