An Organoid-based Functional Precision Medicine Trial in Osteosarcoma (PREMOST)

An Organoid-based Functional Precision Medicine Trial in Osteosarcoma: PREMOST

The purpose of this study is to examine if we can predict sensitivity of osteosarcoma to different chemotherapy agents using tissue cultures in the laboratory. We know that different chemotherapy agents can be used in the treatment, but not every sarcoma responds to them equally. It is important to understand if testing of the tissue obtained during a routine biopsy or surgery may be useful in selecting appropriate treatments. In addition, additional testing of the tumor, including genetic testing, will help us to understand osteosarcoma better.

Study Overview

• Status: Recruiting
• Conditions: Osteosarcoma
• Intervention / Treatment: Other: standard of care biopsy; Other: standard of care biopsy

Detailed Description

Investigators successfully established a miniaturized system that allows the setup of hundreds of wells and perform assays with minimal manipulation. The adapted geometry used to plate tumor cells in Matrigel, to generate mini-rings around the rim of the wells. This is attained by plating single-cell suspensions obtained from a cell line or a surgical specimen pre-mixed with cold Matrigel in a ring shape around the rim in 96-well plates. Rings can be established using a single-well or multichannel pipette. Cancer cell lines grown in mini-ring format give rise to organized tumor organoids that recapitulate features of the original histology. Treatment protocols and readouts for the mini-ring approach have been optimized. Seeding cells takes place on day 0, 2-3 days are allowed to establish organoids and it is followed by two consecutive daily drug treatments. The assay is flexible and can be easily adapted to single treatments followed by longer incubations, multiple consecutive recurring treatments, multi-drug combinations, or other screening strategies. Assays were implemented to quantify drug response by measuring cell viability after staining of live organoids with specific dyes followed by imaging. The pipeline has been extended to sarcomas: the team characterized organoids established from over 120 sarcoma biopsies, resections, and metastasectomies. Sarcoma organoids showed patient-specific growth characteristics and subtype-specific histopathology. Organoid sensitivity correlated with diagnostic subtype, patient age at diagnosis, lesion type, prior treatment history, and disease trajectory for a subset of the compounds screened. Organoid screening can provide information to facilitate optimal drug selection, avoid ineffective therapies, and mirror patient outcomes in sarcoma.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Summer Swearingen; Phone Number: (424) 766-9349; Email: SSwearingen@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA / Jonsson Comprehensive Cancer Center
      • Contact: Summer Swearingen; Phone Number: 424-766-9349; Email: SSwearingen@mednet.ucla.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Osteosarcoma is the most common primary bone malignancy of childhood and adolescence with a bimodal age distribution and a secondary peak in the 6th and 7th decades of life. The standard of care for localized disease is neoadjuvant cytotoxic chemotherapy followed by primary resection and adjuvant cytotoxic chemotherapy. Introduction of chemotherapy in the treatment of patients with osteosarcoma resulted in a significant improvement in the overall survival, but further improvement is needed.

Currently, 5-year survival rate is 65 - 70%; for de novo metastatic disease or recurrent disease, 5-year survival rate is <30%. Recurrent or metastatic osteosarcomas are usually resistant to standard of care, and treatment options for refractory osteosarcomas are extremely limited.

Description

Inclusion / exclusion criteria - Group1:

- Patients without diagnosis of osteosarcoma and whose imaging studies are suggestive of osteosarcoma and who are planned to undergo biopsy or surgery for diagnostic purposes

Inclusion / exclusion criteria - Group 2:

- Patients whose imaging studies are suggestive of metastatic osteosarcoma and who are planned to undergo biopsy or surgery for diagnostic purposes

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1: local tumor; patients with localized osteosarcoma who are scheduled to undergo diagnostic biopsy and are planned for surgical excision of the primary tumor	Other: standard of care biopsy; Image-guided or surgical biopsy of the lesion that is suspected to be osteosarcoma in a patient with localized disease (Group 1); Other: standard of care biopsy; Image-guided or surgical biopsy or excision of the lesion that is suspected to be recurrent or metastatic osteosarcoma (Group 2).
Group 2: metastatic disease; patients with metastatic osteosarcoma who are scheduled to undergo either biopsy or surgery of metastatic disease	Other: standard of care biopsy; Image-guided or surgical biopsy of the lesion that is suspected to be osteosarcoma in a patient with localized disease (Group 1); Other: standard of care biopsy; Image-guided or surgical biopsy or excision of the lesion that is suspected to be recurrent or metastatic osteosarcoma (Group 2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
organoids from initial biopsy	To assess the feasibility of establishing organoids from initial biopsy and from postsurgical sample in patients with osteosarcoma, both in patients with localized disease and metastatic disease	two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
drug sensitivity of organoids	To compare drug sensitivity of organoids established from the original biopsy to drug sensitivity of organoids established from the surgical excision of the primary tumor after neoadjuvant chemotherapy	two years
degree of necrosis in the tumor	To correlate the degree of necrosis in the tumor obtained by the surgical excision of the primary tumor after neoadjuvant chemotherapy with the chemotherapeutic drug sensitivity in the organoids.	two years
clinical benefit	To correlate the magnitude of clinical benefit in patients with metastatic osteosarcoma treated with systemic chemotherapy with the chemotherapeutic drug sensitivity in the organoids established from biopsy or surgical excision of metastatic disease.	two years

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Investigators: Principal Investigator: Alice Soragni, PhD, University of California at Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: September 26, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Osteosarcoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Osteosarcoma
• Other Study ID Numbers: 23-001212

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No