Patient-derived Xenograft (PDX) Modeling to Test Drug Response for High-grade Osteosarcoma

Patient-derived Xenograft (PDX) Modeling to Test Drug Response for High-grade Osterosarcoma

By obtaining clinical specimens from participants with high-grade bone and soft tissue sarcomas 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 individualized cancer treatment options

Study Overview

• Status: Not yet recruiting
• Conditions: Osteosarcoma
• Intervention / Treatment: Other: Molecular Profiling & In Vivo drug testing in PDX

Detailed Description

Patient-derived xenografts (PDX) 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. PDX have been employed to inform clinical decision-making in small studies, which have shown high concordance between individual PDX and patient responses to therapy. While encouraging, the role of this approach in bone and soft tissue sarcomas and in the context of genomic drug matching strategies remains undefined. This has created an opportunity to evaluate the utility of PDX as clinical predictors to direct the use of chemo- and targeted therapies in combination with comprehensive genomic and epigenetic analysis for patients with bone and soft tissue sarcomas.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Tingting Ren, PhD; Phone Number: 86-10-88324470; Email: tumorcenter@163.com
• Study Contact Backup: Name: Yidan Zhang, MD; Phone Number: 86-13810330739; Email: zhangyidan@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with high-grade osteosarcoma referred to, or being treated at Peking University People's Hostpital.

Description

Inclusion Criteria:

1. Age >18 years;
2. Diagnosis confirmed histologically and reviewed centrally;
3. Prior treatment (completed >4 weeks before trial entry) consisted of standard high-grade osteosarcoma chemotherapy agents including doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide; metastatic relapsed and unresectable progressive disease (PD);
4. Eastern Cooperative Oncology Group performance status 0-1 with a life expectancy >3 months;
5. Adequate renal, hepatic, and hemopoietic function;
6. Normal or controlled blood pressure;
7. Surgery and/or radiotherapy completion at least 1 month before enrollment.

Exclusion Criteria:

1. Central nervous system metastasis;
2. Have had other kinds of malignant tumors at the same time;
3. Cardiac insufficiency or arrhythmia;
4. Uncontrolled complications, such as diabetes mellitus and so on;
5. Coagulation disorders;
6. Urine protein≥ ++;
7. Pleural or peritoneal effusion that needs to be handled by surgical treatment;
8. Combined with other infections or wounds.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Osteosarcoma; Osteosarcoma patients with metastatic relapsed or unresectable progressive disease (total n= up to 20) following resection of the primary lesion and adjuvant chemotherapy.	Other: Molecular Profiling & In Vivo drug testing in PDX; Molecular profiling of host tumour sample and PDX will be performed and analyzed by an expert panel. In vitro drug testing using organoid culture generation may also be performed if sufficient fresh tissue is available. Matched treatment recommendation based on profiling and in vivo PDX drug testing results will be made, if available.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of drug sensitive PDX 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 2 years

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Wei Guo, MD, PhD, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2018
• Primary Completion (Anticipated): January 31, 2020
• Study Completion (Anticipated): January 31, 2025

Study Registration Dates

• First Submitted: November 25, 2017
• First Submitted That Met QC Criteria: November 29, 2017
• First Posted (Actual): November 30, 2017

Study Record Updates

• Last Update Posted (Actual): November 30, 2017
• Last Update Submitted That Met QC Criteria: November 29, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Osteosarcoma; Patient-derived xenograft
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Osteosarcoma
• Other Study ID Numbers: 2017PHB278-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No