Clinical Trial: Protocol for the Study and Treatment of Participants With Intraocular Retinoblastoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Protocol for the Study and Treatment of Participants With Intraocular Retinoblastoma

Brief Summary:

The primary objective of this protocol is to evaluate the response rate of bilateral disease participants who have at least one eye with advanced intra-ocular retinoblastoma (stratum B) using upfront therapy with chemotherapy delivered directly to the eye. The main biology objective is to improve our understanding of the biology and tumorigenesis (how tumor develops) of retinoblastoma when biology specimens are available. As clinicians, the primary goal of the investigators for children with retinoblastoma is to provide optimal therapy using multiple treatment approaches [chemotherapy (into the vein and directly into membrane of eyeball), cryotherapy (freeze and destroy tumor), thermotherapy (laser or heat to destroy tumor), radiation therapy, and surgical removal of eye if needed) in an attempt to preserve the eye and vision whenever possible, while still curing the disease. Therefore, all children with non-metastatic retinoblastoma at St. Jude will be offered enrollment on this study.

PRIMARY OBJECTIVE:

  • To evaluate the response (complete + partial response) rate of bilateral disease participants who have at least one eye with advanced intraocular retinoblastoma (Stratum B) to two upfront courses of therapy consisting of subconjunctival carboplatin and systemic topotecan.

SECONDARY OBJECTIVES:

  • To evaluate the ocular survival of eyes and event-free survival of participants by strata.
  • To prospectively analyze intraocular disease tissue for participants with at least one eye undergoing enucleation in order to identify the mechanism of RB1 bi-allelic inactivation. Participants may undergo upfront enucleation (due to advance

    Detailed Summary:

    Participants will be stratified into four main treatment groups, depending on whether retinoblastoma is present in one or both eyes and disease grouping [early or advanced, Reese-Ellsworth (R-E) group I-V, and International Classification A-E]. Additionally, participants will be invited to participate in exploratory research objectives that address cognitive and functional development of children with retinoblastoma, the pharmacokinetics of topotecan in young children, and evaluation of ototoxicity, including genetic analysis.

    TREATMENT PLAN

    STRATUM A:

    • Children ≥ or equal to 6 months old at time of enrollment - 8 courses of vincristine and carboplatin, given at 3-4 week intervals.
    • Infants < 6 months old at time of enrollment - Therapy will consist of six courses of chemotherapy; three courses of vincristine and carboplatin, given at 3-4 week intervals, alternating with 3 cycles of vincristine and topotecan, given at 3-4 week intervals.

    Focal treatments will be administered at the discretion of the treating team. Focal therapies will include cryotherapy, laser photocoagulation, thermo-therapy and plaque radiotherapy.

    STRATUM B:

    • Participants without extensive sub-retinal (SR) seeding, treatment will consist of two up-front courses of vincristine and topotecan, given at 3-4 week intervals.
    • Participants without SR seeding: ≥ or equal to partial response after 2 cycles, will receive three additional courses of vincristine-topotecan (VT) and six courses of vincristine-carboplatin
      Sponsor: St. Jude Children's Research Hospital

      Current Primary Outcome: Response rate (complete or partial response) [ Time Frame: After two upfront courses of chemotherapy (approximately two months after patient enrollment) ]

      Stratum B patients, those Stratum B patients who had no significant subretinal seeding and received vincristine and topotecan are not evaluable for this primary objective.


      Original Primary Outcome: Response rate (complete or partial response) [ Time Frame: After two upfront courses of chemotherapy (approximately two months after patient enrollment) ]

      Stratum B patients, those Stratum B patients who had no significant subtretinal seeding and received vincristine and topotecan are not evaluable for this primary objective.


      Current Secondary Outcome:

      • ocular survival [ Time Frame: at end of study (approximately three years after the last patient enrollment) ]
        Ocular survival per eye will be defined as the time interval from study enrollment to date of enucleation or to date of last contact for eyes that have not been enucleated.
      • Event-free survival [ Time Frame: at end of study (approximately three years after the last patient enrollment) ]
        Event-free survival per eye will be defined as the time interval from date on study to date of first event (where an event includes external beam radiation or enucleation) or to the date of last contact for eyes without events.
      • The mechanism (or frequencies) for each RB1 biallelic inactivation [ Time Frame: At end of study (approximately one year after the last patient is enrolled on study) ]
        The tumor tissue samples will be obtained from participant who has at least one eye undergoing enucleation.


      Original Secondary Outcome: Same as current

      Information By: St. Jude Children's Research Hospital

      Dates:
      Date Received: January 31, 2013
      Date Started: June 19, 2013
      Date Completion: June 30, 2022
      Last Updated: March 30, 2017
      Last Verified: October 2016