A Pilot Study of Intra-Ophthalmic Artery Topotecan Infusion for the Treatment of Retinoblastoma

Inclusion Criteria:

1. Age: 15 years of age or younger

2. Diagnosis: Patients with untreated Group C/D/E unilateral Retinoblastoma at
presentation without an indication for immediate enucleation (neovascular glaucoma or
orbital pain) (Stratum A), or patients with a history of bilateral retinoblastoma and
recurrent and/or refractory intraocular retinoblastoma where chemotherapy, external
beam radiation and/or enucleation remain the only known option for disease control
(Stratum B).

3. Therapeutic Options: Chemotherapy, External Beam Radiation therapy and/or
Enucleation

4. Lansky ≥ 50 for patients ≤ 10 years of age; Karnofsky ≥ 50 for patients > 10 years of
age. Patients who are unable to walk because of paralysis, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the
performance score.

5. Prior Therapy: Stratum A: No prior therapy is allowed. Stratum B: Patients must
have local relapsed/refractory disease after receiving standard upfront therapy
involving at least one chemotherapeutic regimen. There is no limit to prior
chemotherapeutic regimens permitted. Prior radiation therapy is permitted.

6. Patients must have recovered from the acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study, as described below:

- Myelosuppressive chemotherapy: patients must not have received myelosuppressive
chemotherapy within 3 weeks of study enrollment.

- Biologic therapies: Patients must not have received biologic anti-cancer agents
within one week of study enrollment.

- Radiation therapy: Four weeks must have elapsed since external beam radiation
therapy, if given.

7. Adequate Bone Marrow Function Defined as:

- Peripheral absolute neutrophil count (ANC) greater than or equal to 750/uL

- Platelet count greater than or equal to 75,000/uL (transfusion independent,
defined as not receiving platelet transfusions within a 7-day period prior to
enrollment)

- Hemoglobin greater than or equal to 8.0 gm/dL (may receive RBC transfusions)

8. Adequate Renal Function Defined as:

-Maximum serum creatinine based on age as follows: 1 to < 2 years- 0.6 mg/dL; 2 to <
6 years - 0.8 mg/dL; 6 to < 10 years- 1 mg/dL; 10 to < 13 years- 1.2 mg/dL; 13 to 15
years- 1.5 mg/dL for boys and 1.4 mg/dL for girls.

OR

Creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/1.73 m2

9. Adequate Liver Function Defined As:

- Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 x upper
limit of normal (ULN) for age

- SGPT (ALT) less than or equal to 5 x upper limit of normal (ULN) for age

- Serum albumin greater than or equal to 2 g/dL

10. Informed Consent: All patients and/or their parents or legal guardians must sign a
written informed consent. Assent, when appropriate, will be obtained according to
institutional guidelines.

11. Patients of child-bearing potential must have a negative pregnancy test and agree to
use an effective birth control method (abstinence is an acceptable form of birth
control).

Exclusion Criteria:

1. Extra-ocular retinoblastoma or retinoblastoma involving the anterior chamber

2. Retinoblastoma that could otherwise be treated with laser therapy, cryotherapy, or
plaque therapy only

3. Structural brain abnormality

4. Uncontrolled infection, defined as requiring intravenous antibiotics at the time of
enrollment

5. Concomitant Medications

- Growth factors that support platelet or white cell number or function must not
have been administered within 3 days prior to enrollment.

- Patients who are currently receiving non-FDA approved drugs, or who have
received a non-FDA approved drug within 7 days prior to enrollment, are
ineligible.

- Patients who are currently receiving other anti-cancer agents are ineligible.

6. Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible.