Retinoblastoma Biomarker Study

Melanoma Clinical Trial

Official title:

Retinoblastoma Biomarker Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00342797
• Other study ID #: 999993033
• Secondary ID: OH93-NC-N033
• Status: Completed
• Start date: November 17, 1993
• Est. completion date: March 6, 2024

Study information

• Verified date: March 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Retinoblastoma is a rare pediatric ocular tumor caused by germline and/or somatic mutations in the tumor suppressor gene RB1. Survivors of retinoblastoma, particularly those with the hereditary form of the disease (germline RB1 mutations) are highly susceptible to developing additional malignancies, which are a major cause of morbidity and mortality. Since 1984, REB has followed a cohort of 2136 (including 1,995 one-year) retinoblastoma survivors to investigate the contributions of treatment and genetic risk factors to second cancer etiology. The last systematic follow-up for second cancer incidence and cause-specific mortality was completed in 2009. As the cohort ages, we now propose to conduct another interview survey to collect information on newly diagnosed second cancers. Additionally, we propose to expand collection of germline DNA for additional molecular studies in survivors. Retinoblastoma survivors have now entered adult ages when epithelial tumors would be expected to occur with greater frequency. Given that the somatic mutations in the RB1 pathway have been identified in several epithelial tumors (bladder, brain, breast, esophagus, liver, lung, prostate) in addition to sarcomas, it is important to collect new information on these epithelial tumors, and to investigate whether the previously identified high risks of sarcomas and melanoma will persist as the cohort ages. Additionally, our understanding of genetic susceptibility to second cancers is limited. Given that this is the only cohort of long-term survivors of retinoblastoma being followed in the U.S., combined with the leadership role of REB in the study of second cancers, continued follow-up of this cohort will provide unique clinical and epidemiologic data on the long-term cumulative risk of second cancers in this distinctive cohort of childhood cancer survivors.

Description:

Retinoblastoma is a rare pediatric ocular tumor caused by germline and/or somatic mutations in the tumor suppressor gene RB1. Survivors of retinoblastoma, particularly those with the hereditary form of the disease (germline RB1 mutations) are highly susceptible to developing additional malignancies, which are a major cause of morbidity and mortality. Since 1984, REB has followed a cohort of 2136 (including 1,995 one-year) retinoblastoma survivors to investigate the contributions of treatment and genetic risk factors to second cancer etiology. The last systematic follow-up for second cancer incidence and cause-specific mortality was completed in 2009. As the cohort ages, we now propose to conduct another interview survey to collect information on newly diagnosed second cancers. Additionally, we propose to expand collection of germline DNA for additional molecular studies in survivors. Retinoblastoma survivors have now entered adult ages when epithelial tumors would be expected to occur with greater frequency. Given that the somatic mutations in the RB1 pathway have been identified in several epithelial tumors (bladder, brain, breast, esophagus, liver, lung, prostate) in addition to sarcomas, it is important to collect new information on these epithelial tumors, and to investigate whether the previously identified high risks of sarcomas and melanoma will persist as the cohort ages. Additionally, our understanding of genetic susceptibility to second cancers is limited. Given that this is the only cohort of long-term survivors of retinoblastoma being followed in the U.S., combined with the leadership role of REB in the study of second cancers, continued follow-up of this cohort will provide unique clinical and epidemiologic data on the long-term cumulative risk of second cancers in this distinctive cohort of childhood cancer survivors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2136
• Est. completion date: March 6, 2024
• Est. primary completion date: March 6, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years and older

Eligibility

• INCLUSION CRITERIA:

Children treated for retroblastoma over the past 30-plus years.

Related Conditions & MeSH terms

• Melanoma
• Retinoblastoma
• Sarcoma

Locations

Country	Name	City	State
United States	National Cancer Institute (NCI)	Bethesda	Maryland
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts
United States	Social Scientific Systems, Inc.	Durham	North Carolina
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Kleinerman RA, Schonfeld SJ, Sigel BS, Wong-Siegel JR, Gilbert ES, Abramson DH, Seddon JM, Tucker MA, Morton LM. Bone and Soft-Tissue Sarcoma Risk in Long-Term Survivors of Hereditary Retinoblastoma Treated With Radiation. J Clin Oncol. 2019 Dec 10;37(35):3436-3445. doi: 10.1200/JCO.19.01096. Epub 2019 Oct 17. — View Citation

Kleinerman RA, Tucker MA, Sigel BS, Abramson DH, Seddon JM, Morton LM. Patterns of Cause-Specific Mortality Among 2053 Survivors of Retinoblastoma, 1914-2016. J Natl Cancer Inst. 2019 Sep 1;111(9):961-969. doi: 10.1093/jnci/djy227. — View Citation

Wong JR, Morton LM, Tucker MA, Abramson DH, Seddon JM, Sampson JN, Kleinerman RA. Risk of subsequent malignant neoplasms in long-term hereditary retinoblastoma survivors after chemotherapy and radiotherapy. J Clin Oncol. 2014 Oct 10;32(29):3284-90. doi: 10.1200/JCO.2013.54.7844. Epub 2014 Sep 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mutation in RB1 gene	Location of mutation in the RB1 gene	once
Primary	Subsequent Cancer	Risk of subsequent cancer in relation to prior treatment and RB1 mutation	At least one year after retinoblastoma