What side effects are associated with this type of intervention?

Episcleral topotecan, a topoisomerase I inhibitor, is associated with side effects such as myelosuppression (anemia, neutropenia, thrombocytopenia), gastrointestinal disturbances (nausea, vomiting, diarrhea), and fatigue. Other common treatments for retinoblastoma, including chemotherapy agents like carboplatin, vincristine, and etoposide, can cause similar hematologic toxicities, neuropathy, and increased risk of infections. Radiation therapy can lead to local side effects such as cataracts, dry eye, and potential damage to surrounding tissues.

What prior FDA approvals exist?

There is limited information on prior FDA approvals specifically for the treatment of Retinoblastoma involving Topoisomerase I inhibitors like Episcleral Topotecan. Historically, treatments for Retinoblastoma have included chemotherapy agents such as carboplatin, vincristine, and etoposide, as well as localized treatments like laser therapy and cryotherapy. The use of Topoisomerase I inhibitors in this context is still under investigation, as evidenced by the ongoing clinical trial for Episcleral Topotecan.

What other types of research exist?

Promising novel alternatives to episcleral topotecan for retinoblastoma patients include intra-arterial chemotherapy (IAC) with agents like melphalan, topotecan, and carboplatin, as well as intravitreal chemotherapy (IViC) for vitreous seeds. Additionally, targeted therapies such as small-molecule inhibitors and immunotherapies are being explored in clinical trials and may offer new treatment options.

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Topoisomerase I inhibitor

Topotecan Episcleral Plaque for Retinoblastoma (STEP-RB Trial)

Q: What is the mechanism of action of this treatment?

Topotecan, used in the treatment of Retinoblastoma, works by inhibiting Topoisomerase I, an enzyme crucial for DNA replication. This inhibition leads to DNA damage and cell death, particularly effective in rapidly dividing cancer cells. Melphalan, another common treatment, is an alkylating agent that cross-links DNA strands, preventing cell division and leading to apoptosis. These mechanisms are vital for Retinoblastoma patients as they target the cancer cells' ability to proliferate, thereby controlling tumor growth and preserving vision.

Phase 1

Recruiting

Led By Brenda Gallie

Research Sponsored by The Hospital for Sick Children

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Study eye must have vision potential and no clinical features suggestive of high risk of extraocular extension

Lansky play score ≥ 50 if <16 years of age; Karnofsky performance scale of ≥ 50 if ≥16 years of age

Must not have

Participants with reported allergy to topotecan, camptothecin or derivatives thereof

Participants known to have clinical or EUA evidence of extraocular extension

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 9 weeks

Awards & highlights

No Placebo-Only Group

Approved for 5 Other Conditions

All Individual Drugs Already Approved

Summary

This trial tests a new treatment for children with eye cancer that hasn't fully responded to other treatments. It uses a small device placed on the eye to slowly release a cancer-fighting drug directly where it's needed.

Who is the study for?

Children under 18 with active residual or recurrent retinoblastoma in one eye after first-line therapy, or those newly diagnosed with certain types of retinoblastoma without prior treatment. They must have good organ function and performance status, and girls able to have children must use effective birth control. Kids can't join if they have cancer spread outside the eye, allergies to topotecan, other treatments within 3 weeks before the trial starts, uncontrolled illnesses, or are pregnant/breastfeeding.

What is being tested?

The safety and effectiveness of a new treatment called Topotecan Episcleral Plaque is being tested for kids with a type of eye cancer called retinoblastoma. This study involves gradually increasing doses to find out how much medicine can be given safely while checking how well it works against the cancer.

What are the potential side effects?

Possible side effects may include reactions related to topotecan such as lowered blood cell counts which increases infection risk, potential liver or kidney issues due to drug processing in these organs. Specific side effects will be monitored closely during this early phase trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My study eye can potentially see and doesn't show signs of cancer spreading outside the eye.

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I can do most activities if under 16, or care for myself if 16 or older.

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My eye cancer came back or didn't fully go away after first treatment.

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I am under 18 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am allergic to topotecan, camptothecin, or similar drugs.

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My eye cancer has spread beyond the eye.

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I have a known metastatic disease and other ongoing health issues.

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I haven't had a fever or significant illness in the last week.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 9 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~9 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 9 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose and Recommended Phase 2 Dose of topotecan hydrochloride administered as a Chemoplaque to pediatric patients with active Retinoblastoma.

Secondary study objectives

Tumor response to the Chemoplaque as secondary therapy in eye(s) with active retinoblastoma after completion of primary standard of care treatment.

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Phase I single arm trialExperimental Treatment1 Intervention

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Topotecan, used in the treatment of Retinoblastoma, works by inhibiting Topoisomerase I, an enzyme crucial for DNA replication. This inhibition leads to DNA damage and cell death, particularly effective in rapidly dividing cancer cells. Melphalan, another common treatment, is an alkylating agent that cross-links DNA strands, preventing cell division and leading to apoptosis. These mechanisms are vital for Retinoblastoma patients as they target the cancer cells' ability to proliferate, thereby controlling tumor growth and preserving vision.

Synergistic cytotoxicity with 2'-deoxy-5-azacytidine and topotecan in vitro and in vivo.Clinical pharmacokinetics of intra-arterial melphalan and topotecan combination in patients with retinoblastoma.In vitro thermo- and thermochemo-sensitivity of retinoblastoma cells from surgical specimens.