Drug Sensitivity and Mutation Profiling

Drug Sensitivity Testing and Mutation Profiling in Childhood Sarcomas

This study is a prospective, non-randomized observational study. Freshly isolated tumor cells will be tested for chemosensitivity to the standard of care drugs as single agents and in combinations using state-of-the-art viability assay designed for ex-vivo high-throughput drug sensitivity testing (DST). In addition, the genetic profile of the tumor will be obtained from the medical records and correlated with drug response.

Study Overview

• Status: Completed
• Conditions: Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Wilms Tumor; Sarcoma, Spindle Cell; Sarcoma Rhabdoid; Childhood Sarcoma of Soft Tissue

Detailed Description

The excised tumors or a biopsy will be interrogated for sensitivity or resistance to FDA-approved and/or available investigational agents. In addition, normal samples (blood or buccal swab) will be collected for genetic analysis of germline mutations and cancer predisposition markers. The timeframe between the sample acquisition and ex vivo DST results return will be approximately 5-10 working days. All drugs tested in the DST assay will be assigned a hybrid score reflecting the tumor's sensitivity and drug toxicity.

This is an observational study and not a treatment protocol. It will assess how ex vivo drug testing and mutation profiling may predict clinical outcomes (response, survival, or relapse). The treating physician will decide which of the standard treatment options is appropriate independent of the DST results. The results of DST will not be available to the treating physician at the time of decision on the treatment regimen. DST will include all drugs from the standard treatment regimens available for all types of sarcomas

• Study Type: Observational
• Enrollment (Actual): 14

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (ADULT, CHILD)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with newly diagnosed as well as relapsed/refractory sarcomas.

Description

Inclusion Criteria:

• Patients aged 21 years or younger at the time of enrollment on this study of any gender, race, or ethnicity.
• Subjects with suspected or confirmed diagnosis of all types of sarcomas.
• Subjects who are scheduled for or have recently had biopsy or tumor excised (solid tumors) or bone marrow aspirate (blood cancers).
• Subjects are willing to have a blood draw or buccal swab done for the purposes of genetic testing.
• Subjects or their parents or legal guardians willing to sign informed consent.
• Subjects aged 7 to 17 willing to sign assent.

Exclusion Criteria:

• Subjects who do not have malignant tissue available and accessible.
• The amount of excised malignant tissue is not sufficient for ex vivo drug testing and/or genetic profiling.
• Patients with other types of tumors and tumors that have a high (>90%) cure rate with safe standard therapy.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Patients with newly diagnosed as well as relapsed/refractory sarcomas.; The investigators intend to enroll newly diagnosed or refractory/relapsed pediatric patients with all types of sarcomas where tumor tissue would be available for ex vivo drug screening and genomic profiling. This observational study will assess how ex vivo drug testing and mutation profiling may predict clinical outcomes (response, survival, or relapse). The treating physician will decide which of the standard treatment options is appropriate independent of the DST results. The results of DST will not be available to the treating physician at the time of decision on the treatment regimen. DST will include all drugs from the standard treatment regimens available for all types of sarcomas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To correlate results of drug sensitivity and mutation profiles with clinical outcomes in response to therapy.	Response to therapy (RTT): an event of achieving "partial response" or "complete response" during the study period, based on the best response of the corresponding enrolled patient.	Up to 4 years
To correlate results of drug sensitivity and mutation profiles with clinical outcomes in progression-free survival.	Progression-free survival (PFS): a composite end point defined as the censored event time from enrollment to either disease relapse or mortality. This will be evaluated retrospectively at the end of the study. The investigators will use the two-sample long-rank test to assess the hazard ratio of PFS events between the two groups classified as drug sensitive and insensitive by the DST.The study will enroll 15 patients and it is assumed 50% of these subjects will be classified as drug sensitive based on the DST at the threshold value of 10.	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the predictive value of personalized approach in predicting RTT.	Classification accuracy of DST for predicting the RTT	Up to 4 years
To assess the predictive value of personalized approach in predicting PFS.	Classification accuracy of DST for predicting the PFS The DTS test results will be treated as the continuous classifier, and the binary RTT status for each subject along with the binary PFS status by the end of the study will be used as the binary reference status (with and without RTT/PFS endpoint). The area under the curve (AUC) of the resulting ROC curve will be used a metric for the overall classification accuracy	Up to 4 years

Collaborators and Investigators

• Sponsor: Florida International University
• Collaborators: Nicklaus Children's Hospital f/k/a Miami Children's Hospital; Cornelia T. Bailey Foundation
• Investigators: Principal Investigator: Maggie Fader, MD, Nicklaus Children's Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 17, 2020
• Primary Completion (ACTUAL): December 31, 2022
• Study Completion (ACTUAL): December 31, 2022

Study Registration Dates

• First Submitted: June 25, 2021
• First Submitted That Met QC Criteria: June 30, 2021
• First Posted (ACTUAL): July 9, 2021

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: genomic profiling; ex vivo drug sensitivity assay
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Kidney Neoplasms; Neoplastic Syndromes, Hereditary; Neoplasms, Complex and Mixed; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Myosarcoma; Sarcoma; Sarcoma, Ewing; Osteosarcoma; Rhabdomyosarcoma; Wilms Tumor
• Other Study ID Numbers: 1294510

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