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Drug Sensitivity and Mutation Profiling

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ClinicalTrials.gov Identifier: NCT04956198
Recruitment Status : Recruiting
First Posted : July 9, 2021
Last Update Posted : July 9, 2021
Sponsor:
Collaborators:
Nicklaus Children's Hospital f/k/a Miami Children's Hospital
Cornelia T. Bailey Foundation
Information provided by (Responsible Party):
Diana Azzam, PhD, Florida International University

Brief Summary:
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.

Condition or disease
Ewing Sarcoma Osteosarcoma 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

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Study Type : Observational
Estimated Enrollment : 15 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Drug Sensitivity Testing and Mutation Profiling in Childhood Sarcomas
Actual Study Start Date : November 17, 2020
Estimated Primary Completion Date : November 17, 2022
Estimated Study Completion Date : December 31, 2022


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



Primary Outcome Measures :
  1. To correlate results of drug sensitivity and mutation profiles with clinical outcomes in response to therapy. [ Time Frame: Up to 4 years ]
    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.

  2. To correlate results of drug sensitivity and mutation profiles with clinical outcomes in progression-free survival. [ Time Frame: Up to 4 years ]
    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.


Secondary Outcome Measures :
  1. To assess the predictive value of personalized approach in predicting RTT. [ Time Frame: Up to 4 years ]
    Classification accuracy of DST for predicting the RTT

  2. To assess the predictive value of personalized approach in predicting PFS. [ Time Frame: Up to 4 years ]

    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



Biospecimen Retention:   Samples With DNA
Perform molecular and functional drug testing on blood, biopsy, bone marrow, and tumor samples at relapse.


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Patients with newly diagnosed as well as relapsed/refractory sarcomas.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04956198


Contacts
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Contact: Diana Azzam, PhD 305-348-9043 dazzam@fiu.edu
Contact: Leat Perez, PhD 305-301-6626 leat.perez@nicklaushealth.org

Locations
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United States, Florida
Nicklaus Children's Hospital Recruiting
Miami, Florida, United States, 33155
Contact: Leat Perez    305-301-6626    leat.perez@nicklaushealth.org   
Contact: Daria Salyakina, PhD    306-663-8592    daria.salyakina@nicklaushealth.org   
Sponsors and Collaborators
Florida International University
Nicklaus Children's Hospital f/k/a Miami Children's Hospital
Cornelia T. Bailey Foundation
Investigators
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Principal Investigator: Diana Azzam, PhD Florida International University
Principal Investigator: Daria Salyakina, PhD Nicklaus Children's Hospital
Principal Investigator: Maggie Fader, MD Nicklaus Children's Hospital
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Responsible Party: Diana Azzam, PhD, Assistant Professor, Florida International University
ClinicalTrials.gov Identifier: NCT04956198    
Other Study ID Numbers: 1294510
First Posted: July 9, 2021    Key Record Dates
Last Update Posted: July 9, 2021
Last Verified: June 2021

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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
Keywords provided by Diana Azzam, PhD, Florida International University:
ex vivo drug sensitivity assay
genomic profiling
Additional relevant MeSH terms:
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Sarcoma
Osteosarcoma
Rhabdomyosarcoma
Sarcoma, Ewing
Wilms Tumor
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Complex and Mixed
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Kidney Diseases
Urologic Diseases
Genetic Diseases, Inborn