| Eligibility |
Inclusion Criteria:
Age: Participants must be < 21 years of age.
Diagnosis and Treatment. Participants must have:
Unilateral Group D or earlier-stage intraocular retinoblastoma in which enucleation is a
recommended therapy, with no previous local or systemic therapy for retinoblastoma with
intraocular calcium in the tumor-containing eye by ophthalmic ultrasound or neuroimaging.
OR Active residual or recurrent intraocular retinoblastoma in at least one eye following
completion of first-line therapy (focal therapy for IIRC Group A eyes, or systemic or
intra-arterial chemotherapy).
One eye will be the Study Eye. When participants have two eyes with retinoblastoma, the eye
with worst disease or best vision potential will be designated the Study Eye. There will
only be one eye per child treated in this Phase I study, since treatment of two eyes would
double the systemic dose of drug. The Non-study eye will be treated by standard of care,
with only focal therapy during the Study Period, if required.
Must have demonstrated intraocular calcium in the tumor-containing eye by ophthalmic
ultrasound or by neuroimaging as part of standard retinoblastoma diagnosis.
Study eye must have vision potential, at least light perception vision in the tumor-bearing
eye either with pupil response testing or demonstration of avoidance behavior to light
presentation in the affected eye, and no clinical features suggestive of high risk of
extraocular extension.
Performance Level: Lansky greater than or equal 50 (<16 years of age); Karnofsky
performance scale of >50 (>16 years of age).
Organ Function Requirements:
1. Adequate Bone Marrow Function defined as:
- Peripheral absolute neutrophil count (ANC) greater than or equal 1000/mm3
- Platelet count greater than or equal 100,000/mm3 (transfusion independent,
defined as not receiving platelet transfusions for at least 7 Days prior to
enrollment)
- Hemoglobin greater than or equal 8.0 g/dL at baseline (may receive RBC
transfusions)
2. Adequate Renal Function defined as:
- Creatinine clearance or radioisotope GFR greater than or equal 70ml/min/1.73 m2
or
- A serum creatinine based on age/gender as follows:
Age Maximum Serum Creatinine (mg/dL) Male Female
1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5
1. to < 2 years 0.6 0.6
2. to < 6 years 0.8 0.8
6 to < 7 years 1 1
The threshold creatinine values in this Table were derived from the Schwartz formula
for estimating GFR utilizing child length and stature data published by the CDC.
3. Adequate Liver Function defined as:
- Bilirubin (sum of conjugated + unconjugated) less than or equal 1.5 x upper limit
of normal (ULN) for age.
- SGPT (ALT) less than or equal 110 U/L. For the purpose of this study, the ULN for
SGPT is 45 U/L.
- Serum albumin greater than or requal 2 g/dL.
4. Pregnancy prevention. Females of reproductive potential must agree to the use of
highly effective contraception during study participation and for an additional 40
days after the end of Episcleral Topotecan administration.
5. Informed consent. All participants and/or their parents or legally authorized
representatives must have the ability to understand and the willingness to sign a
written informed consent. Assent, where appropriate, will also be obtained.
Exclusion Criteria
Disease status. Participants known to have any of the following are excluded:
1. tumor involving the optic nerve rim
2. clinical or EUA evidence of extraocular extension
3. evidence of metastatic retinoblastoma
4. existing neuroimaging showing suspicion of, or definitive, optic nerve . invasion,
trilateral retinoblastoma or extra-ocular extension.
Allergy. Participants with reported allergy to topotecan, camptothecin or derivatives
thereof are excluded.
Concomitant treatment. Participants who have received chemotherapy, other focal
retinoblastoma therapy or any other investigational agent within 3 weeks of Episcleral
Topotecan placement are not eligible.
Uncontrolled intercurrent illness. Participants with known uncontrolled intercurrent
illness that, in the investigator's opinion, would put the participant at undue risk or
limit compliance with the study requirements, are not eligible.
Febrile illness. Participants with clinically significant febrile illness (as determined by
the investigator) within one week prior to initiation of protocol therapy are excluded.
Pregnancy and lactation. Females of reproductive potential must have a negative serum
pregnancy test within 72 hours prior to initiation of protocol therapy. Due to the unknown
but potential risk for adverse events (AEs) in nursing infants secondary to treatment of
the mother with the study agents, breastfeeding must be discontinued if the mother is
treated on study.
Compliance. Any condition of diagnosis that could in the opinion of the Principal
Investigator or delegate interfere with the participant's ability to comply with the study
instruction, might confound the interpretation of the study results, or put the participant
at risk.
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