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Study Summary
No. COGARET0231:.......Eye; Pediatrics; Solid Tumors......Cynthia E. Herzog......Pediatrics
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Study Summary Title
Study Summary
Number:
COGARET0231
Study Title:A Single Arm Trial of Systemic and Subtenon Chemotherapy for Groups C and D Intraocular Retinoblastoma
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Physician New Patient Referral
Name:Cynthia E. HerzogPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:PediatricsReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-6620
Contact us about clinical trials
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General Information
Disease Group:Eye
Pediatrics
Solid Tumors
Supported By:NCI through COG
Phase of Study:Phase IIIReturn
Visit:
Patients must return for chemotherapy cycles and physical exams on Days 1-3 of
every 28-day cycle.
Treatment
Agents:
Carboplatin
Etoposide
Filgrastim
Vincristine
Home Care:Supportive care only.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
Hospitalization is not expected.
Description/
Intervention:
The goal of this clinical research study is to learn if the drug combination
called CEV (carboplatin, etoposide, and vincristine) when given by vein in
combination with carboplatin into the eye, can help to control Group C and/or
Group D tumors. The side effects of this therapy will also be studied.

Researchers also want to learn what happens if the therapy does not work. For
example, if the tumor goes away and then comes back, doctors want to find out
where the tumor comes back. Researchers want to find out how the tumor changes
after 6 cycles of chemotherapy and if the changes can help to predict the
success of saving the eye. Researchers also want to learn how many eyes with
Group C and D tumors can be saved without eye removal if this therapy does not
work.
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Study Objectives / Outcomes
Primary Aims:
1) To determine the event free survival proportion at 12-months (with an event defined for each eye
individually as the need for non-protocol therapy including non-protocol chemotherapy, enucleation or
any external beam radiation at the eye level) for eyes with Group D retinoblastoma treated with systemic
carboplatin/etoposide/vincristine (CEV), subtenon carboplatin, and local ophthalmic therapy.

Secondary Aims:
1) To determine the event free survival proportion at 12-months (with an event defined for each eye
individually as the need for non-protocol therapy including non-protocol chemotherapy, enucleation or
any external beam radiation at the eye level) for eyes with Group C retinoblastoma treated with systemic
carboplatin/etoposide/vincristine (CEV), subtenon carboplatin, and local ophthalmic therapy.
2) To determine the acute and long-term toxicities associated with the proposed regimens, including visual
outcome and incidence of secondary malignancies.
3) To determine the patterns of failure for Groups C and D with protocol therapy (vitreous versus retinal
versus both as sites of recurrence).
4) To determine predictors of failure including findings at the on study Examination Under Anesthesia (EUA) and response status after six courses of chemotherapy.
5) To determine the percentage of Group C and D eyes separately that can be preserved without enucleation

after failing protocol therapy.
6) To determine the percentage of Group C and D eyes separately that can be preserved without enucleation
after failing protocol therapy.
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Study Status Information
Study Activation / Registration Date:01/26/2009
IRB Review and Approval Date:01/26/2009
Study Type:Phase Iii
Recruitment Status:Closed
Projected Accrual:69
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Only patients less than 18 years of age at study entry are eligible.

2) Patients must be enrolled before treatment begins. Treatment must start within 5 calendar days of study enrollment. Patients will begin treatment within 14 days of fulfilling all eligibility criteria. Tests to determine eligibility must be performed within one week prior to enrollment unless otherwise indicated below.

3) Patients must have bilateral retinoblastoma with at least one eye with Group C or D intraocular retinoblastoma confirmed by ophthalmologic examination under anesthesia done within three weeks of study enrollment.

4) Patients will be registered on study based on the local EUA done for diagnostic purposes prior to study entry. The EUA done at study entry must be done within three weeks prior to study entry. RetCam images must be submitted from the diagnostic EUA. This submission must occur within three weeks after study entry. These images will be centrally reviewed within six weeks from study entry to confirm eligibility and International Classification System for Intraocular Retinoblastoma.

5) Patients must have either Group C or Group D intraocular retinoblastoma in at least one eye. GROUP C = Discrete local disease with minimal subretinal or vitreal seeding: Tumor(s) are discrete; Subretinal fluid, present or past without seeding, involving up to one quarter retina; Local fine vitreous seeding may be present close to discrete tumor. - Local subretinal seeding less than 3 mm (2DD) from the tumor.

6) (#5 continued): GROUP D = Diffuse disease with significant vitreous or subretinal seeding: Tumor(s) may be massive or diffuse; Subretinal fluid, present or past without seeding involving up to total retinal detachment; Diffuse or massive vitreous disease may include "greasy" seeds or avascular tumor masses; Diffuse subretinal seeding may include subretinal plaques or tumor nodules. If a patient is found on central review to have neither a C nor a D eye eligible for study, then the patient will be declared inevaluable and will be removed from the study.

7) Performance level must be a score of 50 or greater. Use Karnofsky for patients > 16 years of age and Lansky for patients < / = 16 years of age.

8) A venous access device (VAD) is suggested but not required for protocol therapy.

9) Patients may have had enucleation of one eye, as long as the remaining eye is either Group C or D. Patients must not have received any prior chemotherapy or radiotherapy.

10) Adequate renal function defined as: (1) Creatinine clearance or radioisotope GFR > / = 70 mL/min/1.73 m^2; OR, (2) maximum serum creatinine (md/dL) based on age/gender as follows: 1 month to < 6 months: 0.4 md/dL; 6 months to < 1 yr: 0.5 md/dL; 1 to < 2 yrs: 0.6 md/dL; 2 to < 6 yrs: 0.8 md/dL; 6 to < 10 yrs: 1 md/dL; 10 to < 13 yrs: 1.2 md/dL; 13 to < 16 yrs: Male: 1.5 md/dL; Female: 1.4 md/dL; > / = 16 yrs: Male: 1.7 md/dL; Female: 1.4 mg/dL.

11) Adequate liver function defined as: 1) Total bilirubin should be less than or equal to 1.5 x upper limit of normal (ULN) for age; and, 2) SGOT (AST) and SGPT (ALT) < 2.5 x upper limit of normal (ULN) for age.

12) Negative serum Beta- HCG in post menarchal females.

13) Use of adequate contraception in males and females of child bearing age.

14) All patients and/or their parents or legal guardians must sign a written informed consent.

15) All institutional, FDA, and NCI requirements for human studies must be met.

Exclusion Criteria:1) Any evidence of extraocular retinoblastoma clinically or by MRI of brain and orbits with and without gadolinium (preferred study) or CT with and without contrast of brain and orbits. This CT or MRI may be done within four weeks prior to study entry.

2) Tumor present on histologic examination at the cut end of the optic nerve on any eye enucleated prior to study entry. Evidence of choroidal and/or optic nerve invasion past the lamina cribosa ARE ALLOWED. Since pathology may not be available at study entry on an enucleated eye, patients may be entered on study pending final pathology report. If histology meets exclusion criteria, then patient will be declared inevaluable and taken off study.

3) Evidence of systemic metastases on bone marrow, lumbar puncture, bone scan, and/or any other additional tests done at study entry (Note: These tests are required only with specific indications.)

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Links
Registration Number: NCT00072384
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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