Clinical Trial: Study of Treatment for Patients With Cancer of the Eye -Retinoblastoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief Summary:

Retinoblastoma is a childhood cancer which affects the retina of the eye. The retina is the light sensitive layer of tissue that lines the back of the eyeball; sends visual messages through the optic nerve to the brain. When only one eye is affected, this is known as unilateral retinoblastoma and when both eyes are affected, it is called bilateral retinoblastoma. Treatment for retinoblastoma is individualized for each patient and is based on the form and the stage of the disease (inside the eye or has moved outside). The main goal is always to cure the cancer, and save the life of the child. Treatments are also designed with the hope of saving the vision, while completely destroying the tumor. Therapies may involve surgery, chemotherapy, radiation, and other treatments called focal treatments. Focal treatments may be laser therapy, freezing, or heat treatments meant to shrink and kill the tumor.

In this study, researchers want to investigate how different participants respond to different therapies that are individualized specifically for them. Participants will be divided into three main groups, depending on whether the disease is unilateral or bilateral, and the stage of the disease. One of the main objectives of the study is to investigate how advanced tumors in children with bilateral disease respond to a new combination of chemotherapy with topotecan and vincristine, with G-CSF support. In order to improve results, some children with very advanced disease may receive carboplatin chemotherapy given around the eye at the same time that they receive topotecan by vein. Also, because children with retinoblastoma are diagnosed so early in life and the vision may be significantly impaired, this study will investigate how children develop and how the brain adjusts and compensates for the visual deficits. Finally, this study also investigates the biology of retinoblastoma, in

Detailed Summary:

This study will determine the following:

PRIMARY OBJECTIVE:

  • To estimate the ocular survival and event-free survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.

SECONDARY OBJECTIVES:

  • To estimate the ocular survival of eye and event-free survival of eye of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.
  • To estimate the ocular survival and event free survival of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments.
  • To estimate the ocular survival and event free survival of eye of patients with advanced intraocular retinoblastoma (R-E IV-V) not responding to the vincristine/topotecan window, with a combination of vincristine, carboplatin, etoposide, and periocular carboplatin, with intensive focal treatments.
  • To estimate the ocular survival and event-free survival of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments.
  • Sponsor: St. Jude Children's Research Hospital

    Current Primary Outcome: Stratum B Response to Window Therapy [ Time Frame: Six weeks post window therapy ]

    The primary outcome is to estimate the proportion of stratum B patients responding to 2 courses of window therapy consisting of vincristine and topotecan. Complete Response is the complete regression of all apparent tumor masses in the funduscopic examination and by MRI and ultrasound (US). Partial Response is defined as greater than 50% (but less than 100%) reduction of the tumor masses in the funduscopic examination and by US and MRI, without the appearance of any new lesions. The response must persist for at least 4 weeks. Stratum A and C did not receive window therapy.


    Original Primary Outcome:

    • To find out how many participants with retinoblastoma will respond to the individualized therapies given in this study
    • To learn more about the changes in vision in patients with retinoblastoma
    • To learn more about the intellectual, social and emotional development of children with retinoblastoma during the first five years of life
    • To learn more about the genetic make up of retinoblastoma tumors


    Current Secondary Outcome:

    • Stratum B Response Rate of Early Stage Eyes to Window Therapy [ Time Frame: Six weeks post window therapy. ]
      To estimate the proportion of early stage eyes defined as Reese-Ellsworth Group I, II, or III eyes, that responded to 2 courses of window therapy which consisted of vincristine and topotecan
    • Relationship Between Topotecan Clearance (CL) and CYP3A4/5 Genotype in Stratum B Participants. [ Time Frame: Courses 1, 2, 5, and 8 ]
      Blood samples for pharmacokinetic studies were collected at 0 hour (pre-dose), 5 minutes, 1.5 and 2.5 hours after the end of topotecan dose on Course 1 Day 1, Course 2 Day 1, and if further studies were needed, Course 5 Day 1 and Course 8 Day 1. A blood sample for pharmacogenetic studies was collected during the course of therapy on protocol.
    • Relationship Between Topotecan Clearance (CL) and ABCG2/B1 Genotype in Stratum B Participants. [ Time Frame: Courses 1, 2, 5, and 8 ]
      Blood samples for pharmacokinetic studies were collected at 0 hour (pre-dose), 5 minutes, 1.5 and 2.5 hours after the end of topotecan dose on Course 1 Day 1, Course 2 Day 1, and if further studies were needed, Course 5 Day 1 and Course 8 Day 1. A blood sample for pharmacogenetic studies was collected during the course of therapy on protocol.
    • Event-free Survival of Stratum B Patients Responding to Window Treatment [ Time Frame: From date on-study to an event or last follow-up ]

      To estimate the 5-year event-free (EFS) survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.

      Event-free survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of first event (an event includes external beam radiation or enucleation) of advanced stage eyes, time to first event will be used for the analysis. Event-free survival will be estimated using the method of Kaplan and Meier.

    • Ocular Survival of Stratum B Patients Responding to Window Treatment [ Time Frame: From date on-study to an event or last follow-up ]

      To estimate the 5-year ocular survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.

      Ocular survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of enucleation of advanced stage eye or date of last follow-up, for patients with two advanced stage eyes, the time to the first enucleation will be used for analysis. Ocular survival will be estimated using the method of Kaplan and Meier. Standard error is 5-year ocular survival

    • Event-free Survival of Eyes in Stratum B Patients Responding to Window Treatment [ Time Frame: From date on-study to an event or last follow-up ]

      To estimate the 5-year event-free survival (EFS) of eyes of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.

      Event-free survival of eye will be defined per eye as the time interval from date on study to date of first event (an event includes external beam radiation or enucleation) or to last follow-up date for eyes without events. Event-free survival of eye will be estimated using the method of Kaplan and Meier. Standard error is 5-year EFS.

    • Ocular Survival of Eyes in Stratum B Patients Responding to Window Treatment [ Time Frame: From date on-study to an event or last follow-up ]

      To estimate the 5-year ocular survival of eye of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.

      Ocular survival of eye will be defined per eye as the time interval from date on study to date of enucleation or date of last follow-up. Ocular survival of eye will be estimated using the method of Kaplan and Meier. Standard error is 5-year ocular survival.

    • Event-free Survival of Stratum B Patients Not Responding to Window Treatment [ Time Frame: From date on-study to an event or last follow-up ]
      To estimate the 5-year event free su

      Original Secondary Outcome:

      Information By: St. Jude Children's Research Hospital

      Dates:
      Date Received: September 12, 2005
      Date Started: February 2005
      Date Completion: September 2021
      Last Updated: April 11, 2017
      Last Verified: June 2016