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

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ClinicalTrials.gov Identifier: NCT02732860
Recruitment Status : Recruiting
First Posted : April 11, 2016
Last Update Posted : September 21, 2018
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

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

Condition or disease Intervention/treatment
Colorectal Neoplasms Colorectal Cancer Breast Cancer Breast Neoplasms Ovarian Cancer Ovarian Neoplasm Other: Molecular Profiling & In Vivo drug testing in pPDX and organoid cultures

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.

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Study Type : Observational
Estimated Enrollment : 105 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Evaluation of Freshly Implanted Cancers in Mice to Test Drug Response in Matching Host
Study Start Date : December 2015
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020


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 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.




Primary Outcome Measures :
  1. 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.

  2. Rate of results reporting [ Time Frame: up to 5 years ]
  3. Rate of pPDX engraftment [ Time Frame: up to 2 years ]

Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. Correlation between pPDX and organoid drug sensitivities [ Time Frame: up to 5 years ]

Biospecimen Retention:   Samples With DNA
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)


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02732860


Contacts
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Contact: David Cescon, MD 416-946-2245 Dave.Cescon@uhn.ca

Locations
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Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Lailah Ahmed    416-946-4501 ext 3638    lailah.ahmed@uhn.ca   
Principal Investigator: David Cescon, MD         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: David Cescon, MD Princess Margaret Cancer Centre

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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02732860     History of Changes
Other Study ID Numbers: REFLECT-001
First Posted: April 11, 2016    Key Record Dates
Last Update Posted: September 21, 2018
Last Verified: September 2018
Keywords provided by University Health Network, Toronto:
personalized patient-derived xenografts (pPDX)
molecular profiling
epigenetic analysis
drug sensitivity testing
triple negative
metastatic
serous
Additional relevant MeSH terms:
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Colorectal Neoplasms
Ovarian Neoplasms
Breast Neoplasms
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Colonic Diseases
Endocrine Gland Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Breast Diseases
Skin Diseases