Clinical trial NCT04959097: RB Liquid Biopsy Biorepository
Official title: Retinoblastoma Patient Clinical Database, Liquid Biopsy and Tissue Biorepository
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Retinoblastoma
Retinoblastoma Bilateral
Retinoblastoma Unilateral
Keywords: Retinoblastoma
RB
Ocular oncology
Aqueous humor
Lead sponsor: Children's Hospital Los Angeles
Sponsor class: OTHER
First posted: 2021-07-13
Enrollment: 800
Sex: ALL
Minimum age (years): 0
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients, age 0 days to 18 years, with a diagnosis unilateral or bilateral retinoblastoma (RB) treated at CHLA who have biospecimens taken for research during the course of treatment.

Brief 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.

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Correlation of Ocular Salvage (eye saved) with biomarkers
timeFrame: through study completion, a minimum of 12 months after diagnosis and average of 24 months
measure: Identification of RB1 (RB Transcriptional Corepressor 1) gene mutations from the AH liquid biopsy
timeFrame: through study completion, a minimum of 12 months after diagnosis and average of 24 months
Secondary outcomes:
measure: Correlation of High-Risk Histopathologic Features with presence of biomarkers
timeFrame: through study completion, a minimum of 12 months after diagnosis and average of 24 months (only if the eye is enucleated)
measure: Correlation of class of Seeding with presence of biomarkers
timeFrame: through study completion, a minimum of 12 months after diagnosis and average of 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
Study officials:
affiliation: Children's Hospital Los Angeles
name: Jesse L Berry, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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: The Surrogate Tumor Biopsy for Retinoblastoma. Mol Cancer Res. 2018 Nov;16(11):1701-1712. doi: 10.1158/1541-7786.MCR-18-0369. Epub 2018 Jul 30.
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 Aug;18(8):1166-1175. doi: 10.1158/1541-7786.MCR-19-1262. Epub 2020 May 20.
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. Ophthalmic Genet. 2020 Dec;41(6):526-532. doi: 10.1080/13816810.2020.1799417. Epub 2020 Aug 17.
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):30. doi: 10.1167/tvst.9.10.30. eCollection 2020 Sep.
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 Monitoring of Retinoblastoma: The Aqueous Humor Liquid Biopsy. Cancers (Basel). 2021 Mar 13;13(6):1282. doi: 10.3390/cancers13061282.