Ex Vivo Drug Sensitivity Testing and Mutation Profiling

Completed

• Conditions: Refractory Childhood Malignant Germ Cell Neoplasm; Recurrent Childhood Brainstem Glioma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Childhood Hodgkin Lymphoma; Recurrent Childhood Ependymoma; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Childhood Acute Myeloid Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Brain Tumor

• Registration Number: NCT03860376
• Lead Sponsor: Florida International University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2019-02-11
• Study Start: 2019-02-21
• Study First Submitted QC: 2019-02-28
• Study First Posted: 2019-03-01
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-08
• Last Update Posted: 2023-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of patients that receive DST-guided treatmens	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).

Secondary Outcome Measures

Name	Time	Method
Assessing Objective Response Rate	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)
Assessing Progression-Free Survival (PFS)	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)
Assessing Previous vs Trial PFS Ratio (PFS2/PFS1)	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).

Trial Locations

Locations (1)

Nicklaus Children's Hospital; 🇺🇸 Miami, Florida, United States