Ex Vivo Drug Sensitivity Testing and Mutation Profiling

NCT03860376 | Completed

• 2 other identifiers: 11869198LA05
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Percentage of patients that receive DST-guided treatmens

  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 Outcomes (3)

• Assessing Objective Response Rate

  Up to 4 years

• Assessing Progression-Free Survival (PFS)

  Up to 4 years

• Assessing Previous vs Trial PFS Ratio (PFS2/PFS1)

  Up to 4 years

Study Arms (1)

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.

Eligibility Criteria

• Age: 1 Day - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Florida International University: lead
• Nicklaus Children's Hospital f/k/a Miami Children's Hospital: collaborator

Study Sites (1)

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Related Publications (2)

• 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.

  PMID: 34738048 RESULT

• Acanda De La Rocha AM, Berlow NE, Fader M, Coats ER, Saghira C, Espinal PS, Galano J, Khatib Z, Abdella H, Maher OM, Vorontsova Y, Andrade-Feraud CM, Daccache A, Jacome A, Reis V, Holcomb B, Ghurani Y, Rimblas L, Guilarte TR, Hu N, Salyakina D, Azzam DJ. Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers. Nat Med. 2024 Apr;30(4):990-1000. doi: 10.1038/s41591-024-02848-4. Epub 2024 Apr 11.

  PMID: 38605166 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

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

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Dendritic Cell Sarcoma, Interdigitating; Familial ependymoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Histiocytic Disorders, Malignant; Histiocytosis; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Diana Azzam, PhD

  Florida International University

  PRINCIPAL INVESTIGATOR

• Daria Salyakina, PhD

  Nicklaus Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: March 1, 2019
• Study Start: February 21, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: May 10, 2023

Record last verified: 2023-05

Locations

US (1)