Symptoms and General Pathology

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Disease Attributes

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Acute Graft Versus Host Disease

Childhood Acute Lymphoblastic Leukemia

Brain Tumor, Childhood

Childhood Brain Stem Glioma

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Chronic Myeloproliferative Disorders

Neuroepithelioma

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.

Diana Azzam, PhD

Daria Salyakina, PhD

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.

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.

Perform molecular and functional drug testing on blood, biopsy, bone marrow and tumor samples at relapse.

Ex Vivo Drug Sensitivity Testing and Mutation Profiling

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

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).

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)

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)

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).

Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Florida International University

Assistant Professor

Spots Global Cancer Trial Database for refractory childhood malignant germ cell neoplasm