RB Liquid Biopsy Biorepository

Retinoblastoma Clinical Trial

— rbliqbx  

Official title:

Retinoblastoma Patient Clinical Database, Liquid Biopsy and Tissue Biorepository

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04959097
• Other study ID #: CHLA-17-00248
• Status: Recruiting
• Start date: January 1, 2017
• Est. completion date: December 31, 2030

Study information

• Verified date: February 2024
• Source: Children's Hospital Los Angeles
• Contact: Jesse L Berry, MD
• Phone: 323-361-4510
• Email: jberry[@]chla.usc.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Retinoblastoma (RB) is a primary eye cancer that forms in the back of the eye of infants and toddlers. Traditionally, RB is diagnosed without a biopsy; tumor can only be studied once an eye has been surgically removed. Given this limitation, we use aqueous humor (AH), the clear fluid in the front of the eye to detect specific markers, or information, that comes from the tumor itself.

Description:

Retinoblastoma (RB) is a primary intraocular malignancy that forms in the retina of infants and toddlers. Traditionally, RB is diagnosed without tissue as direct tumor biopsy is prohibited due to risk of extraocular spread; tissue can only be obtained once an eye has been surgically removed. Given this limitation, there are no eye-specific molecular biomarkers in current clinical practice for RB. The lack of in vivo molecular data without removing the eye limits our ability to prognosticate clinical outcomes and develop personalized treatment plans. It also limits our understanding of intratumoral dynamics throughout therapy. The aqueous humor (AH) is a high-yield source of tumor-derived nucleic acid that can be utilized as a liquid biopsy in eyes with retinoblastoma. Detection of biomarkers from the AH may be used to prognosticate the likelihood of eye salvage and in the future may facilitate targeted, patient-centered therapies based on molecular biomarkers. OBJECTIVES: 1. Systematically and prospectively record accurate and complete data regarding the clinical presentation, treatment, and outcomes of patients diagnosed with RB. 2. Collect, bank, preserve, and analyze biomaterials including AH, blood and saliva from patients with RB. 3. Correlate phenotypic data with genotypic findings from human biomaterials in retinoblastoma patients to identify clinically relevant biomarkers

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 18 Years

Eligibility

Inclusion Criteria:

• All patients, age 0 days to 18 years, with a diagnosis unilateral or bilateral retinoblastoma (RB) seen at CHLA (Children's Hospital Los Angeles).

Exclusion Criteria:

• Patients referred for second opinions only and not treated at CHLA for any reason.

Related Conditions & MeSH terms

• Retinoblastoma
• Retinoblastoma Bilateral

Locations

Country	Name	City	State
United States	Children's Hospital Los Angeles	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (7)

Berry JL, Xu L, Kooi I, Murphree AL, Prabakar RK, Reid M, Stachelek K, Le BHA, Welter L, Reiser BJ, Chevez-Barrios P, Jubran R, Lee TC, Kim JW, Kuhn P, Cobrinik D, Hicks J. Genomic cfDNA Analysis of Aqueous Humor in Retinoblastoma Predicts Eye Salvage: Th — View Citation

Berry JL, Xu L, Murphree AL, Krishnan S, Stachelek K, Zolfaghari E, McGovern K, Lee TC, Carlsson A, Kuhn P, Kim JW, Cobrinik D, Hicks J. Potential of Aqueous Humor as a Surrogate Tumor Biopsy for Retinoblastoma. JAMA Ophthalmol. 2017 Nov 1;135(11):1221-1230. doi: 10.1001/jamaophthalmol.2017.4097. — View Citation

Berry JL, Xu L, Polski A, Jubran R, Kuhn P, Kim JW, Hicks J. Aqueous Humor Is Superior to Blood as a Liquid Biopsy for Retinoblastoma. Ophthalmology. 2020 Apr;127(4):552-554. doi: 10.1016/j.ophtha.2019.10.026. Epub 2019 Oct 31. — View Citation

Polski A, Xu L, Prabakar RK, Kim JW, Shah R, Jubran R, Kuhn P, Cobrinik D, Hicks J, Berry JL. Cell-Free DNA Tumor Fraction in the Aqueous Humor Is Associated With Therapeutic Response in Retinoblastoma Patients. Transl Vis Sci Technol. 2020 Sep 30;9(10):3 — View Citation

Xu L, Kim ME, Polski A, Prabakar RK, Shen L, Peng CC, Reid MW, Chevez-Barrios P, Kim JW, Shah R, Jubran R, Kuhn P, Cobrinik D, Biegel JA, Gai X, Hicks J, Berry JL. Establishing the Clinical Utility of ctDNA Analysis for Diagnosis, Prognosis, and Treatment — View Citation

Xu L, Polski A, Prabakar RK, Reid MW, Chevez-Barrios P, Jubran R, Kim JW, Kuhn P, Cobrinik D, Hicks J, Berry JL. Chromosome 6p Amplification in Aqueous Humor Cell-Free DNA Is a Prognostic Biomarker for Retinoblastoma Ocular Survival. Mol Cancer Res. 2020 — View Citation

Xu L, Shen L, Polski A, Prabakar RK, Shah R, Jubran R, Kim JW, Biegel J, Kuhn P, Cobrinik D, Hicks J, Gai X, Berry JL. Simultaneous identification of clinically relevant RB1 mutations and copy number alterations in aqueous humor of retinoblastoma eyes. Op — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of Ocular Salvage (eye saved) with biomarkers	We aim to evaluate whether any identifiable molecular biomarkers (e.g. chromosomal alterations or tumor fraction) in the aqueous or blood can predict ocular salvage, or the likelihood of saving the eye with therapy	through study completion, a minimum of 12 months after diagnosis and average of 24 months
Primary	Identification of RB1 (RB Transcriptional Corepressor 1) gene mutations from the AH liquid biopsy	We aim to identify both somatic and germline RB1 gene mutations in the AH	through study completion, a minimum of 12 months after diagnosis and average of 24 months
Secondary	Correlation of High-Risk Histopathologic Features with presence of biomarkers	We aim to evaluate whether any identifiable molecular biomarkers in the aqueous or blood can predict the presence of high risk histopathologic features that are known to increase risk of metastatic disease	through study completion, a minimum of 12 months after diagnosis and average of 24 months (only if the eye is enucleated)
Secondary	Correlation of class of Seeding with presence of biomarkers	We aim to evaluate whether any identifiable molecular biomarkers in the aqueous or blood are associated with the presence of type of seeding	through study completion, a minimum of 12 months after diagnosis and average of 24 months