Hyper-Personalized Medicine Using Patient Derived Xenografts (PDXovo) for Metastatic Solid Tumors

• Conditions: Kidney Neoplasm; Carcinoma, Renal Cell; Metastatic Solid Tumor

• Registration Number: NCT04602702
• Lead Sponsor: Sunnybrook Health Sciences Centre

Brief Summary

The Investigators will use novel PDX (patient-derived xenograft) technology to form xenografts using material from metastatic solid tumor patients. Xenografts will be treated with a panel of drugs to determine which agent(s) yield the greatest anti-tumor effect on the xenograft.

Detailed Description

The goal is to use PDXovos, which are chick embryos cultivated in an ex ovo fashion that will act as a xenograft host, for drug paneling. Chick embryos as a PDX host model system offer multiple advantages, such as increased tumor take rates, rapid drug testing, a short evaluation timeframe, and an undeveloped adaptive immune system. Collectively, these advantages allow for implantation of tumor xenografts, subsequent growth in vivo, subsequent drug challenge, and subsequent evaluation for anti-tumor effects.

Patients with metastatic forms of solid tumors will be enrolled regardless of subtype. Metastases will be provided either via metastasectomy or needle core biopsy of metastatic deposits. Spinal and intracranial metastases will be included. Thoracentesis and paracentesis fluid samples yielding tumor tissue will also be included.

Tissue will be processed and briefly cultured in vitro. Upon authentication and expansion to a suitable number of cells, xenografts will be formed in the chick embryo pre-clinical model. After implantation (2 days later), drug treatments will be applied topically to each xenograft's surface. Drug treatments are: sunitinib, pazopanib, axitinib, temsirolimus, cabozantinib, gemcitabine (N\>18/treatment group).

Evaluation of xenografts for anti-tumor effects will be performed via ultrasound imaging (changes in tumor volume and tumor vascularity) and confirmed by histology (H\&E, TUNEL, CD31+ microvessel density). Treatments will be compared to vehicle control (5% DMSO in saline) treated xenografts. ANOVA (2-way, p\<0.01, bon ferroni alpha corrected) analysis will be performed to identify treatments that lead to the greatest decrease in tumor volume and tumor vascularity (ultrasound imaging metrics). Agents identified will not be used to intervene in clinical care. Objective response rates with clinically chosen drug in each patient will be compared to the corresponding PDX drug panel results using kappa analysis.

Study Timeline

• Study First Submitted: 2020-09-10
• Study First Submitted QC: 2020-10-23
• Study First Posted: 2020-10-26
• Study Start: 2020-12-01
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-24
• Last Update Posted: 2022-04-05
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective Response	3-9 months	Complete Response, Partial Response
Progressive Disease Response	3-9 months
Stable Disease Response	3-9 months

Trial Locations

Locations (1)

Odette Cancer Centre; 🇨🇦 Toronto, Ontario, Canada