Medpedia

• Retinoblastoma
• Retinal Neoplasm

Inclusion Criteria:
-  Must have newly diagnosed intraocular retinoblastoma, previously untreated. Patients
previously diagnosed with unilateral retinoblastoma treated surgically (or with focal
therapies), who develop asynchronous involvement of the contralateral eye, will be
eligible for study.
-  Must have a life expectancy of at least 8 weeks.
-  Must have Performance Status (ECOG) of 0-2.
-  Patients must have an adequate liver function, as defined by bilirubin less than or
equal to 3 x normal, and SGOT and SGPT less than or equal to 3x normal.
-  Patients must have adequate renal function as defined by serum creatinine less than
or equal to 3x normal for age.
-  Legal guardians must sign an informed consent indicating that they are aware of this
study, its possible benefits, and toxic side effects. Legal guardians will be given a
copy of the consent form.
Exclusion Criteria:
-  Previously treated patients
-  Presence of metastatic disease or orbital involvement
-  Patients must not have an invasive infection at time of protocol entry.

This study will determine the following:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. To estimate the ocular survival of eye and event-free survival of eye of patients with
early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin
with intensive focal treatments.

7. To estimate the response rate of early stage eyes (R-E I-III) in patients with
contralateral advanced disease treated with vincristine and topotecan.

8. To estimate the ocular survival and event-free survival of early stage eyes (R-E I-III)
of patients with contralateral advanced disease treated with vincristine and topotecan.

9. To describe the outcome of intraocular retinoblastoma with respect to the new
International Classification for Intraocular Retinoblastoma and the AJCC.

10. To describe primary visual cortex function in patients with unilateral and bilateral
retinoblastoma.

11. To describe the cognitive, adaptive, and social/emotional development of children with
retinoblastoma.

12. To describe changes in the pineal gland during treatment in patients with bilateral
retinoblastoma.

13. To provide insight into molecular pathogenesis of retinoblastoma.

14. To describe the incidence and type of germline mutations of the RB gene in patients
with retinoblastoma.

15. To assess the relation between CYP3A4/5 genotype and the pharmacokinetics and
pharmacodynamics of topotecan.

16. To assess the relation between ABCG2 genotype and the pharmacokinetics and
pharmacodynamics of topotecan.

17. To determine if carboplatin can produce changes in cochlear function that are
detectable with measurement of otoacoustic emissions.

18. To evaluate the need for and feasibility of starting early intervention support during
the first year after the diagnosis of retinoblastoma.

• Procedure: Enucleation
  Enucleation (possibly associated with all treatment strata/arms. For Stratum A, patients with bilateral disease will have surgery to remove the advanced eye before chemotherapy, or patients that have disease progression after chemotherapy my have surgery to remove the affected eye. For Stratum B, Surgical removal of the affected eye may be required in cases of disease progression For Stratum C, first intervention is removal of the affected eye.
• Drug: Vincristine, Carboplatin
  (Stratum A subjects receive 8 courses every 3-4 weeks, Stratum B subjects receive this combination for Courses 3, 4, 6, 7, 9, and 10 after the window, if they respond to window therapy) Vincristine dosage< 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1.
• Procedure: Focal Therapies
  Method will be at the discretion of the treating team, used after second course of chemotherapy. Cryotherapy- freezing of affected tissue, Laser photocoagulation- using lasers to destroy affected tissue, Thermotherapy and thermochemotherapy- using heat or heat/chemotherapy combination to destroy diseased tissue, and Episcleral plaque brachytherapy- radiation insertions in the diseased area to destroy affected tissue.
• Radiation: External Beam Radiation
  44-46 Gy administered using standard practices , limiting dose to normal tissues to subjects with recurrent or progressive disease not considered controllable with focal treatments, Stratum B subjects with suspected active disease after completing therapy, or patients considered to have high-risk disease.
• Drug: Vincristine + Topotecan
  (Stratum B subjects receive two up-front courses of vincristine and topotecan, given in 21-day intervals, then those who respond receive 3 additional courses (courses 5, 8, and 11) after the window. Dosages are the same for both window and subsequent courses: Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Topotecan: TSE of 140 ± 20 ng/ml*hr, daily for 5 consecutive days, infused over 30 minutes.
• Drug: Vincristine + Carboplatin + Etoposide
  Stratum B patients that do not respond to window receive 6 courses of this combination. Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1 Etoposide, < 12 months of age: 3.3 mg/kg/d i.v. days 1 - 3, ≥ 12 months of age: 100 mg/m2/d i.v. days 1 - 3
• Drug: Vincristine + Cyclophosphamide + Doxorubicin
  (High risk Stratum C patients in courses 2, 4, and 6 after enucleation, intermediate risk stratum C patients for four consecutive courses after enucleation) Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Cyclophosphamide: < 12 months of age: 40 mg/kg i.v. day 1, ≥ 12 months of age: 1,200 mg/m2 i.v. day 1, MESNA 200 mg/m2 at 0, 3, 6, and 9 hours Doxorubicin < 12 months of age: 1.5 mg/kg i.v. day 1, ≥ 12 months of age: 45 mg/m2 i.v. day 1
• Drug: Vincristine+Carboplatin+Etoposide
  High risk Stratum C patients in courses 1, 3, and 5 after enucleation: Vincristine: < 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1 Etoposide, < 12 months of age: 3.3 mg/kg/d i.v. days 1 - 3, ≥ 12 months of age: 100 mg/m2/d i.v. days 1 - 3
• Procedure: Periocular carboplatin
  Periocular (subtenon) carboplatin 20 mg, one injection, in courses 5, 8, and 11 in patients responding to the VT window, and in courses 1, 3, and 6 of VCE in patients not responding to the VT window, when active vitreous disease is present. Carboplatin 20 mg will be diluted in 2 mL of NS or D5W and given by subtenon administration while the patient is under general anesthesia.
• Other: G-CSF
  G-CSF (5 mcg/kg/day), will be administered starting 24-36 hours after the completion of each course of chemotherapy, for 7 to 10 days, until ANC is > 2,000/mL in one occasion after the expected nadir.

• To find out how many participants with retinoblastoma will respond to the individualized therapies given in this study
  5 years
  Safety Issue: Yes
• To learn more about the changes in vision in patients with retinoblastoma
  5 years
  Safety Issue: Yes
• To learn more about the intellectual, social and emotional development of children with retinoblastoma during the first five years of life
  5 years
  Safety Issue: No
• To learn more about the genetic make up of retinoblastoma tumors
  5 years
  Safety Issue: No

• Ibrahim Qaddoumi, M.D.
  Principal Investigator, St. Jude Children's Research Hospital

• St. Jude Children's Research Hospital
  Memphis, Tennessee, 38105, United States
  Recruiting
  Ibrahim Qaddoumi, MD

  (866) 278-5833

  info@stjude.org

  Investigators

  • Ibrahim Qaddoumi, MD
    Principal Investigator

• St. Jude Children's Research Hospital
  Lead Sponsor
• United States: Institutional Review Board

• St. Jude Children's Research Hospital
  http://www.stjude.org