Cancer Genome Study Using Samples From Patients Treated on Clinical Trial SHR1020-SHR-1210-II-OS (CSSG-02)

A Study to Assess the Therapeutic Efficacy in Advanced Osteosarcoma Patients In the Clinical Trial of SHR1020-SHR-1210-II-OS (Famitinib and Camrelizumab on Chemo-refractory Osteosarcoma) Based on Genomic Analyses of Tumor Specimens

RATIONALE: Studying samples of tumor tissue from patients with advanced osteosarcoma refractory to chemotherapy in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to osteosarcma treatment combining anti-angiogenesis tyrosine kinase inhibitors and anti-PD-1 antibody.

PURPOSE: This research study is looking at the cancer genome using tumor samples from patients with advanced stage osteosarcoma treated on clinical trial SHR1020-SHR-1210-II-OS.

Study Overview

• Status: Completed
• Conditions: Osteosarcoma
• Intervention / Treatment: Other: cytology specimen

Detailed Description

OBJECTIVES:

To investigate the clinical relevance of conducting comprehensive molecular analyses on clinically annotated high-quality tumor specimens from patients with advanced stage osteosarcoma.

OUTLINE: This is a single-center study.

Biological specimens are collected from participating clinical site and analyzed by transcription profiling of RNA and microRNA; detection of DNA copy number changes and chromosomal rearrangements; epigenetic modifications analyses; and sequencing of genomic segments, genes, and regulatory regions to assess sequence variation. Clinical information associated with each specimen donor is also collected.

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
    • Beijing, Beijing, China
      • Peking University Shougang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients have histologically proven metastatic or locally advanced osteosarcoma, reviewed by the Pathology Committee of Peking University People's Hospital, and are not amenable to curative-intent surgery. Previous systemic chemotherapy had failed to prevent the exacerbation of disease, including high-dose methotrexate (HD-MTX), doxorubicin (ADM), cisplatin (DDP) with/without ifosfamide (IFO). Tumors have to be measurable with computed tomography scan or magnetic resonance imaging, per RECIST, version 1.1. Patients undergo collection of tissue samples for genomic analysis via mass spectrometry, PCR, and microarray.

Description

Inclusion Criteria:

• Diagnosis of high-grade osteosarcoma
• refractory to chemotherapy and intended to receive famitinib and camrelizumab following the protocols of SHR1020-SHR-1210-II-OS
• Available tumor tissue samples collected before study drug and after first progression
• Must have matching frozen samples of normal tissue and blood

Exclusion Criteria:

• Patients with concurrent malignancy; patients with prior or concurrent malignancy will be allowed as long as the treating physician considers it unlikely to impact the clinical outcome of the patient
• Serious medical illness including but not limited to uncontrolled congestive heart failure, uncontrolled angina, myocardial infarction or cerebrovascular event with 6 months of registration, history of chronic active hepatitis or history of human immunodeficiency virus (HIV) or an active bacterial infection will not be eligible
• Pregnant or lactating women

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
comprehensive genomic analysis group; Patients undergo collection of tissue samples for genomic analysis via mass spectrometry, PCR, and microarray. The therapy patients received would not be based on the results of the genomic analysis.	Other: cytology specimen; Biopsy and Genetic: DNA analysis;Genetic: RNA analysis;Genetic: microarray analysis; Genetic: mutation analysis; Genetic: polymorphism analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor mutation burden	NGS analysis, based on total exon sequencing of the specimen. Identification and characterization of tumor mutation burden.	2 years
T cell-inflamed gene expression profile (GEP)	IFN-g-related mRNA profile	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
single nucleotide variants (SNVs)	NGS analysis, based on total exon sequencing of the specimen	2 years
short insertions and deletions (indels)	NGS analysis, based on total exon sequencing of the specimen	2 years
copy-number variants (CNVs)	NGS analysis, based on total exon sequencing of the specimen	2 years

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.; OrigiMed

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2019
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: May 14, 2019
• First Submitted That Met QC Criteria: June 23, 2019
• First Posted (Actual): June 25, 2019

Study Record Updates

• Last Update Posted (Actual): June 3, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: famitinib; camrelizumab; tumor mutation burden; genomic biomarkers; PD-L1 expression; Tcell-inflamed gene expression profile (GEP)
• 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: PKUPH-sarcoma 07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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