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

Breast Cancer Clinical Trial

— REFLECT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02732860
• Other study ID #: REFLECT-001
• Status: Recruiting
• Start date: December 2015
• Est. completion date: January 4, 2025

Study information

• Verified date: December 2023
• Source: University Health Network, Toronto
• Contact: David Cescon, MD
• Phone: 416-946-2245
• Email: Dave.Cescon[@]uhn.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: January 4, 2025
• Est. primary completion date: January 4, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Colorectal Cancer
• Colorectal Neoplasms
• Neoplasms
• Ovarian Cancer
• Ovarian Neoplasm
• Ovarian Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure of drug sensitive pPDX to a panel of drugs as a predictor of clinical response in matched host	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
Primary	Rate of results reporting		up to 5 years
Primary	Rate of pPDX engraftment		up to 2 years
Secondary	Comparison of actionable alterations identified in clinical and pPDX samples	Genomic alterations identified using the Ion Proton System for Next-Generation Sequencing (NGS).	up to 5 years
Secondary	Number of patients with molecular abnormalities in pPDX as identified via NGS eliciting clinical responses while receiving matched treatments.	Overall accuracy of clinical responses as assessed by RECIST criteria in patient tumor.	up to 5 years
Secondary	Correlation between pPDX and organoid drug sensitivities		up to 5 years