Clinical trial NCT03860376: Ex Vivo Drug Sensitivity Testing and Mutation Profiling
Official title: Personalized Ex Vivo Drug Screening and Genomics Profiling to Guide Individualized Treatments for Children With Relapsed or Refractory Solid Tumors and Leukemias
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Large Cell Lymphoma
Refractory Childhood Acute Lymphoblastic Leukemia
Refractory Childhood Hodgkin Lymphoma
Refractory Childhood Malignant Germ Cell Neoplasm
Recurrent Childhood Brain Tumor
Recurrent Childhood Brainstem Glioma
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Soft Tissue Sarcoma
Recurrent Childhood Ependymoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Gliosarcoma
Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Keywords: ex vivo drug sensitivity assay
genomic profiling
Lead sponsor: Florida International University
Sponsor class: OTHER
Collaborators: name: Nicklaus Children's Hospital f/k/a Miami Children's Hospital
First posted: 2019-03-01
Enrollment: 25
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Chemorefractory and/or relapsed pediatric cancer patients with no alternative treatment options.

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.

Eligibility 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 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.

Primary outcomes:
measure: Percentage of patients that receive DST-guided treatmens
timeFrame: Up to 4 years
Secondary outcomes:
measure: Assessing Objective Response Rate
timeFrame: Up to 4 years
measure: Assessing Progression-Free Survival (PFS)
timeFrame: Up to 4 years
measure: Assessing Previous vs Trial PFS Ratio (PFS2/PFS1)
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
Study officials:
affiliation: Florida International University
name: Diana Azzam, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nicklaus Children's Hospital
name: Daria Salyakina, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Acanda De La Rocha AM, Fader M, Coats ER, Espinal PS, Berrios V, Saghira C, Sotto I, Shakya R, Janvier M, Khatib Z, Abdella H, Bittle M, Andrade-Feraud CM, Guilarte TR, McCafferty-Fernandez J, Salyakina D, Azzam DJ. Clinical Utility of Functional Precision Medicine in the Management of Recurrent/Relapsed Childhood Rhabdomyosarcoma. JCO Precis Oncol. 2021 Oct 27;5:PO.20.00438. doi: 10.1200/PO.20.00438. eCollection 2021. No abstract available.