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

April 28, 2026 updated by: University Health Network, Toronto

Prospective Evaluation of Freshly Implanted Cancers in Mice to Test Drug Response in Matching Host

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Princess Margaret Cancer Centre
        • Principal Investigator:
          • David Cescon, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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:

  • Molecular Profiling will be performed on clinical sample
  • pPDX generation for in vivo drug testing
  • In vitro organoid culture generation (if sufficient fresh tissue available)
  • Identifying an actionable genomic alteration and drug making a matched treatment therapy recommendation.
Other: Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures
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.
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:

  • Molecular Profiling will be performed on clinical sample
  • pPDX generation for in vivo drug testing
  • In vitro organoid culture generation (if sufficient fresh tissue available)
  • Identifying an actionable genomic alteration and drug making a matched treatment therapy recommendation.
Other: Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures
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.
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:

  • Molecular Profiling will be performed on clinical sample
  • pPDX generation for in vivo drug testing
  • In vitro organoid culture generation (if sufficient fresh tissue available)
  • Identifying an actionable genomic alteration and drug making a matched treatment therapy recommendation.
Other: Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures
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.
Other tumor types

Other selected tumor types at the discretion of the PI (n= up to 30)

After the screening procedures confirms patient eligibility:

  • Molecular Profiling will be performed on clinical sample
  • pPDX generation for in vivo drug testing
  • In vitro organoid culture generation (if sufficient fresh tissue available)
  • Identifying an actionable genomic alteration and drug making a matched treatment therapy recommendation.
Other: Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure of drug sensitive pPDX to a panel of drugs as a predictor of clinical response in matched host
Time Frame: up to 5 years
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
Time Frame: up to 5 years
up to 5 years
Rate of pPDX engraftment
Time Frame: up to 2 years
up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of actionable alterations identified in clinical and pPDX samples
Time Frame: up to 5 years
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.
Time Frame: up to 5 years
Overall accuracy of clinical responses as assessed by RECIST criteria in patient tumor.
up to 5 years
Correlation between pPDX and organoid drug sensitivities
Time Frame: up to 5 years
up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: David Cescon, MD, Princess Margaret Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Estimated)

January 4, 2027

Study Completion (Estimated)

January 4, 2027

Study Registration Dates

First Submitted

February 10, 2016

First Submitted That Met QC Criteria

April 4, 2016

First Posted (Estimated)

April 11, 2016

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REFLECT-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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