Hyper-Personalized Medicine Using Patient Derived Xenografts (PDXovo) for Renal Cell Carcinoma Patients

Titre officiel

Investigating the Potential of Short-Term Patient Derived Xenografts for Personalized Medicine for Patients With Renal Cell Carcinoma: A Non-Interventional Clinical Trial

Sommaire:

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

Description de l'essai

Primary Outcome:

• Objective Response
• Stable Disease Response
• Progressive Disease Response

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 tumour take rates, rapid drug testing, a short evaluation timeframe, and an undeveloped adaptive immune system. Collectively, these advantages allow for implantation of tumour xenografts, subsequent growth in vivo, subsequent drug challenge, and subsequent evaluation for anti-tumour effects. Patients with metastatic forms of renal cell carcinoma (RCC) will be enrolled regardless of subtype (chromophobe, clear cell, oncocytoma, papillary 1/2, etc.). Metastates will be provided either via metastasectomy or needle core biopsy of metastatic deposits. Spinal and intracranial metastases will 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-tumour effects will be performed via ultrasound imaging (changes in tumour volume and tumour 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 tumour volume and tumour 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.

Voir cet essai sur ClinicalTrials.gov