Ex Vivo Drug Sensitivity Testing and Mutation Profiling

May 8, 2023 updated by: Diana Azzam, PhD, Florida International University

Personalized Ex Vivo Drug Screening and Genomics Profiling to Guide Individualized Treatments for Children With Relapsed or Refractory Solid Tumors and Leukemias

This study is a prospective, non-randomized feasibility study. Freshly isolated tumor cells from patients will be screened using state-of-the-art viability assay designed for ex vivo high-throughput drug sensitivity testing (DST). In addition, genetic information will be obtained from cancer and normal (germline) tissue and correlated with drug response. This study will provide the platform for informing treating physician about individualized treatment options. The main outcome of this study will be the proportions of the patients whose treatment was guided by the personalized medicine approach.

Study Overview

Detailed Description

PRIMARY OBJECTIVE: The primary objective of the study is to determine feasibility of providing pediatric cancer patients with access to personalized treatment options and clinical management recommendations based on ex vivo drug sensitivity testing (DST) and genomic profiling.

SECONDARY OBJECTIVE: The secondary objective of the study is to compare individual outcomes (response and disease-free survival) in patients with pediatric cancers treated with DST-guided therapy as compared to non-DST guided (conventional) therapy.

EXPLORATORY OBJECTIVE: To explore associations between genetic abnormalities in malignancies and ex vivo drug response.

Study Type

Observational

Enrollment (Actual)

25

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Chemorefractory and/or relapsed pediatric cancer patients with no alternative treatment options.

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 recurrent or refractory cancer
    • Subjects who are scheduled for or have recently had biopsy or tumor excised (solid tumors) or bone marrow aspirate (blood cancers)
    • Subjects 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 the ex vivo drug testing and/or genetic profiling.
  • Patients with newly diagnosed tumors and tumors that have high (>90%) cure rate with safe standard therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Chemorefractory or relapsed patients
We intend to enroll chemorefractory or relapsed pediatric patients with all types of cancers where tumor tissue would be available for ex vivo drug screening and genomic profiling. The results of the drug sensitivity assay and genetic screening will be used to inform treating physician about patient-specific drug sensitivity or resistance guiding best therapy choices.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients that receive DST-guided treatmens
Time Frame: Up to 4 years

This study will be considered successful (feasibility demonstrated) if it is possible to choose and initiate a monotherapy or combination drug regimen based on functional and/or genomics data within 4 weeks in at least 16 out of 25 patients (64%).

To achieve at least 90% power, the null hypothesis will be rejected when at least 16 out of 25 patients receive treatment recommendations through functional and/or genomics data within 4 weeks on the study.

With that outcome, we would have 95% confidence that the true feasibility rate is at least 30% (95% CI: 0.425, 1).

Up to 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessing Objective Response Rate
Time Frame: Up to 4 years
We will assess changes in cohort Objective Response Rate (ORR) by comparing ORR in patients treated with FPM-guided therapy versus ORR in patients treated with non-FPM guided conventional therapy (standard of care)
Up to 4 years
Assessing Progression-Free Survival (PFS)
Time Frame: Up to 4 years
We will assess changes in cohort PFS by comparing PFS in patients treated with FPM-guided therapy versus PFS in patients treated with non-FPM guided conventional therapy (standard of care)
Up to 4 years
Assessing Previous vs Trial PFS Ratio (PFS2/PFS1)
Time Frame: Up to 4 years
We will assess changes in PFS from each patient's previous treatment versus their PFS from the treatment assigned during the trial. Assessments will be made both in the FPM-guided cohort and the non-FPM-guided conventional therapy cohort. Analysis will include both the raw ratio as well as the number of incidences of 30% improved PFS on trial versus previous regimen (PFS2/PFS1 > 1.3x).
Up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Diana Azzam, PhD, Florida International University
  • Principal Investigator: Daria Salyakina, PhD, Nicklaus Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 21, 2019

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

December 31, 2022

Study Registration Dates

First Submitted

February 11, 2019

First Submitted That Met QC Criteria

February 28, 2019

First Posted (Actual)

March 1, 2019

Study Record Updates

Last Update Posted (Actual)

May 10, 2023

Last Update Submitted That Met QC Criteria

May 8, 2023

Last Verified

May 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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