Topotecan Episcleral Plaque for Treatment of Retinoblastoma

NCT04156347 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 3TRB01
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This single-arm, non-randomized, dose escalation phase I clinical trial will assess primarily the safety and secondarily the efficacy of episcleral topotecan in patients with active de novo or recurrent intraocular retinoblastoma in at least one eye following completion of first-line therapy.

Conditions

Retinoblastoma

Outcome Measures

Primary Outcomes (1)

• To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma-Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D).

  To determine the safety and tolerability of Episcleral Topotecan in participants with retinoblastoma.

  9 Weeks

Secondary Outcomes (2)

• To determine systemic exposure by measurement of Topotecan in plasma.

  42 Days

• To preliminarily define the antitumor activity as determine by assessments of tumor reponse;

  42 Days

Study Arms (1)

Phase I Open Label Study

EXPERIMENTAL

Phase I Single Arm

Drug: Episcleral Topotecan

Interventions

Episcleral Topotecan DRUG

Transscleral Topotecan

Also known as: Episcleral Topotecan, Transscleral Topotecan, Sustained Release Episcleral Topotecan, Chemoplaque

Phase I Open Label Study

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Targeted Therapy Technologies, LLC: lead

Study Sites (1)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

MeSH Terms

Conditions

Retinoblastoma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 7, 2019
• Study Start: June 16, 2021
• Primary Completion: October 1, 2024
• Study Completion: October 14, 2024
• Last Updated: October 31, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)