- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04156347
Topotecan Episcleral Plaque for Treatment of Retinoblastoma
A Phase I Study of Sequestered Transscleral, Controlled-Release Topotecan Delivered From an Episcleral Reservoir in Retinoblastoma Eyes
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: David Carpi, MSc
- Phone Number: 949-892-5363
- Email: dcarpi@3tophthalmics.com
Study Contact Backup
- Name: Ricardo Carvalho, MD
- Phone Number: 949-533-0990
- Email: rcarvalho@3tophthalmics.com
Study Locations
-
-
Arizona
-
Phoenix, Arizona, United States, 85016
- Phoenix Children's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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:
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)
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
- to < 2 years 0.6 0.6
- 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.
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.
- 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.
- 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:
- tumor involving the optic nerve rim
- clinical or EUA evidence of extraocular extension
- evidence of metastatic retinoblastoma
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase I Open Label Study
Phase I Single Arm
|
Transscleral Topotecan
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma-Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D).
Time Frame: 9 Weeks
|
To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma.
|
9 Weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To determine systemic exposure by measurement of Topotecan in plasma.
Time Frame: 42 Days
|
To characterize the systemic exposure of episcleral topotecan by quantifying topotecan concentration in plasma.
|
42 Days
|
To preliminarily define the antitumor activity as determine by assessments of tumor reponse;
Time Frame: 42 Days
|
To preliminarily define the antitumor activity as determine by assessment of tumor response.
|
42 Days
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Eye Diseases
- Retinal Diseases
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Eye Diseases, Hereditary
- Eye Neoplasms
- Retinal Neoplasms
- Retinoblastoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Topotecan
Other Study ID Numbers
- 3TRB01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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