Clinical trial NCT02732860: Personalized Patient Derived Xenograft (pPDX) Modeling to Test Drug Response in Matching Host
Official title: Prospective Evaluation of Freshly Implanted Cancers in Mice to Test Drug Response in Matching Host
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colorectal Neoplasms
Colorectal Cancer
Breast Cancer
Breast Neoplasms
Ovarian Cancer
Ovarian Neoplasm
Keywords: personalized patient-derived xenografts (pPDX)
molecular profiling
epigenetic analysis
drug sensitivity testing
triple negative
metastatic
serous
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2016-04-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with TNBC, CRC, HGSOC, or selected other tumour types, referred to, or being treated at Princess Margaret Cancer Centre.

Brief summary: 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

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, 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 criteria: 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.

Primary outcomes:
measure: Measure of drug sensitive pPDX to a panel of drugs as a predictor of clinical response in matched host
timeFrame: up to 5 years
measure: Rate of results reporting
timeFrame: up to 5 years
measure: Rate of pPDX engraftment
timeFrame: up to 2 years
Secondary outcomes:
measure: Comparison of actionable alterations identified in clinical and pPDX samples
timeFrame: up to 5 years
measure: Number of patients with molecular abnormalities in pPDX as identified via NGS eliciting clinical responses while receiving matched treatments.
timeFrame: up to 5 years
measure: Correlation between pPDX and organoid drug sensitivities
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: David Cescon, MD
role: PRINCIPAL_INVESTIGATOR
References: