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

NCT ID: NCT03358628

Last Updated: 2017-11-30

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-02-01
• Study Completion Date: 2025-01-31

Brief Summary

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

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.

Conditions

Osteosarcoma

Keywords

Osteosarcoma; Patient-derived xenograft

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Osteosarcoma

Osteosarcoma patients with metastatic relapsed or unresectable progressive disease (total n= up to 20) following resection of the primary lesion and adjuvant chemotherapy.

Molecular Profiling & In Vivo drug testing in PDX

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

GUO WEI

Chief of Musculoskeltal Tumor Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wei Guo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Central Contacts

Tingting Ren, PhD

Role: CONTACT

Phone: 86-10-88324470

Email: tumorcenter@163.com

Yidan Zhang, MD

Role: CONTACT

Phone: 86-13810330739

Email: zhangyidan@sina.com

Other Identifiers

2017PHB278-01

Identifier Type: -

Identifier Source: org_study_id