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.
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
14
Nicklaus Children's Hospital
Miami, Florida, United States
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.
Time frame: 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.
Time frame: Up to 4 years
To assess the predictive value of personalized approach in predicting RTT.
Classification accuracy of DST for predicting the RTT
Time frame: 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
Time frame: Up to 4 years
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