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Recruiting NCT04959097

Retinoblastoma Patient Clinical Database and Tissue Repository

— Observational Retinoblastoma Retinoblastoma Bilateral Retinoblastoma Unilateral

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
This is an observational study: the protocol does not assign a study treatment.
Who it may be relevant to
Registry conditions: Retinoblastoma, Retinoblastoma Bilateral, Retinoblastoma Unilateral. Basic parameters: 0 years — 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Canada
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Overview

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

Primary outcome measures

  • Correlation of Ocular Salvage (eye saved) with biomarkers [Time frame: through study completion, a minimum of 12 months after diagnosis and average of 24 months]
  • Identification of RB1 (RB Transcriptional Corepressor 1) gene mutations from the AH liquid biopsy [Time frame: through study completion, a minimum of 12 months after diagnosis and average of 24 months]
Secondary outcome measures (2)
  • Correlation of High-Risk Histopathologic Features with presence of biomarkers [Time frame: through study completion, a minimum of 12 months after diagnosis and average of 24 months (only if the eye is enucleated)]
  • Correlation of class of Seeding with presence of biomarkers [Time frame: through study completion, a minimum of 12 months after diagnosis and average of 24 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model
Cohort

Study locations

United States · 8 centers
  • Phoenix Children's Hospital — Phoenix
  • Children's Hospital Los Angeles — Los Angeles
  • Emory University Children's Healthcare of ATL — Atlanta
  • Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago
  • Oregon Health & Science University: Casey Eye Institute — Portland
  • Wills Eye Institute — Philadelphia
  • St. Jude Children's Research Hospital — Memphis
  • Seattle Children's Hospital; University of Washington — Seattle
Canada · 1 center
  • The Hospital for Sick Children (Toronto SickKids) — Toronto

Publications

  • 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. PMID 29049475
  • 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. PMID 31767439
  • 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. PMID 30061186
  • 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. PMID 32434859
  • 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. PMID 32799607
  • 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. PMID 33062393
  • 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. PMID 33805776

Identifiers

NCT: NCT04959097 · CHLA-17-00248 · 5R01CA282759-02 · NCI-2024-03774

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗