What side effects are associated with this type of intervention?

Common treatments for retinoblastoma, such as topoisomerase I inhibitors like topotecan, can cause a range of side effects. These may include ocular toxicity, such as retinal microvascular damage, capillary nonperfusion, and potential neovascularization, which can lead to complications like vitreous hemorrhage and macular edema. Systemic side effects of topotecan can include myelosuppression, leading to neutropenia, anemia, and thrombocytopenia. When administered episclerally, the localized delivery aims to reduce systemic toxicity but may still pose risks of local ocular irritation or inflammation.

What prior FDA approvals exist?

There is limited information on prior FDA approvals specifically for the treatment of Retinoblastoma using topoisomerase I inhibitors like topotecan. However, topotecan has been studied in clinical trials for its efficacy and safety in treating intraocular retinoblastoma. The current trial involving episcleral topotecan aims to assess its safety and efficacy, indicating ongoing research in this area. Broadly, treatments for retinoblastoma have included chemotherapy agents such as vincristine, carboplatin, and etoposide, but specific FDA approvals for topoisomerase I inhibitors in this context are not well-documented.

What other types of research exist?

Promising novel alternatives to episcleral topotecan for retinoblastoma patients include intra-arterial chemotherapy (IAC) with agents such as melphalan, topotecan, and carboplatin, as well as intravitreal chemotherapy for vitreous seeds. Additionally, targeted therapies and immunotherapies, such as those involving monoclonal antibodies and checkpoint inhibitors, are emerging as potential treatments. Gene therapy and novel drug delivery systems are also being explored for their efficacy and safety in treating retinoblastoma.

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Topoisomerase I inhibitor

Topotecan Episcleral Plaque for Retinoblastoma

Phase 1

Waitlist Available

Research Sponsored by Targeted Therapy Technologies, LLC

Eligibility Criteria Checklist

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

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.

Organ Function Requirements:

Must not have

- Existing neuroimaging showing suspicion of, or definitive, optic nerve invasion, trilateral retinoblastoma or extra-ocular extension.

- Tumor involving the optic nerve rim

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 42 days

Awards & highlights

Summary

This trial is testing a new way to treat eye cancer in children using a small device that slowly releases a cancer drug directly onto the eye. It targets kids whose cancer didn't respond to other treatments. The goal is to see if this method is safe and works well without causing too many side effects.

Who is the study for?

This trial is for children and young adults under 21 with retinoblastoma in at least one eye, who have completed first-line therapy. They must have potential vision in the affected eye and meet specific health criteria including adequate bone marrow, kidney, and liver function. Females of childbearing age must use effective contraception.

What is being tested?

The safety and effectiveness of a treatment called episcleral topotecan are being tested on patients with active de novo or recurrent intraocular retinoblastoma. It's a phase I trial where doses will be increased to find the safest dose that can also potentially help treat the cancer.

What are the potential side effects?

While not explicitly listed here, side effects may include typical reactions to chemotherapy such as nausea, fatigue, low blood counts leading to an increased risk of infection or bleeding, kidney or liver issues depending on individual tolerance to topotecan.

Eligibility Criteria

Inclusion Criteria

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

Select...

I have early-stage retinoblastoma in one eye and haven't had treatment for it.

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My organs are functioning well.

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I can do most activities by myself, regardless of my age.

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My bilirubin levels are within the normal range for my age.

Select...

My eye tumor shows calcium deposits on an ultrasound or MRI.

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I am younger than 21 years old.

Exclusion Criteria

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

Select...

My scans show possible or confirmed spread of eye cancer to the optic nerve or beyond.

Select...

My tumor affects the edge of my optic nerve.

Select...

My retinoblastoma has spread beyond my eye.

Select...

My condition does not match any known exclusion criteria.

Select...

I have not had a significant fever or illness in the last week.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 42 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~42 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 42 days for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

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

Secondary study objectives

To determine systemic exposure by measurement of Topotecan in plasma.

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

Side effects data

From 2019 Phase 2 trial • 35 Patients • NCT01931098

78%

Hypertension

67%

Fatigue

44%

Diarrhea

33%

Vomiting

33%

White blood cell decreased

33%

Cognitive disturbance

33%

Dysgeusia

33%

Seizure

33%

Nausea

22%

Weight loss

22%

Muscle weakness left-sided

22%

Anorexia

22%

Cough

22%

Gait disturbance

22%

Headache

22%

Neutrophil count decreased

22%

Pain

11%

Dysphagia

11%

Gastroesophageal reflux disease

11%

Musculoskeletal and connective tissue disorder - Other, specify

11%

Alanine aminotransferase increased

11%

Anemia

11%

Arthralgia

11%

Aspartate aminotransferase increased

11%

Bruising

11%

Depression

11%

Dizziness

11%

Dry mouth

11%

Dry skin

11%

Dysphasia

11%

Fall

11%

Flank pain

11%

Flu like symptoms

11%

Hematuria

11%

Hoarseness

11%

Hypernatremia

11%

Insomnia

11%

Lymphocyte count decreased

11%

Paresthesia

11%

Purpura

11%

Respiratory, thoracic and mediastinal disorders - Other, Congestion

11%

Sinus tachycardia

11%

Sinusitis

11%

Skin and subcutaneous tissue disorders - Other, Lacerations on legs

11%

Sore throat

11%

Spasticity

11%

Urinary urgency

11%

Oral pain

11%

Meningitis

11%

Eye disorders - Other, Left upper quadrant defect

11%

Gastrointestinal disorders - Other, specify

11%

Stroke

11%

Platelet count decreased

11%

Eye disorders - Other, Right Hemianops

11%

Hypoalbuminemia

11%

Hypocalcemia

100%

80%

60%

40%

20%

Study treatment Arm

Glioblastoma or Gliosarcoma With No Prior Bevacizumab Exposure

Glioblastoma or Gliosarcoma With Prior Bevacizumab Exposure

Trial Design

1Treatment groups

Experimental Treatment

Group I: Phase I Open Label StudyExperimental Treatment1 Intervention

Phase I Single Arm

0 / 11Eligibility 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

Common treatments for Retinoblastoma include chemotherapy agents such as topotecan, melphalan, cisplatin, and etoposide. Topotecan works by inhibiting topoisomerase I, an enzyme crucial for DNA replication, leading to DNA damage and cell death. Melphalan is an alkylating agent that cross-links DNA strands, preventing cell division. Cisplatin forms DNA adducts, disrupting DNA synthesis and function, while etoposide inhibits topoisomerase II, causing DNA breaks. These mechanisms are vital for Retinoblastoma patients as they target rapidly dividing cancer cells, aiming to reduce tumor size and prevent metastasis, thereby preserving vision and improving survival rates.

Synergistic cytotoxicity with 2'-deoxy-5-azacytidine and topotecan in vitro and in vivo.In vitro thermo- and thermochemo-sensitivity of retinoblastoma cells from surgical specimens.