Carboplatin + Topotecan for Retinoblastoma

Overseen By Carlos Rodriguez-Galindo, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Must be taking: Chemotherapy

Disqualifiers: Metastatic disease, Invasive infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two chemotherapy drugs, carboplatin and topotecan, in treating retinoblastoma, a type of eye cancer, by delivering them directly to the eye. The goal is to evaluate how well these treatments shrink tumors and preserve the eyesight of children with advanced intraocular retinoblastoma. The study also aims to understand more about the cancer's development by examining tumor samples when available. Children with recently diagnosed retinoblastoma in one or both eyes, who have not yet received treatment, might be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important advancements in retinoblastoma care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of carboplatin and topotecan is generally well-tolerated. Studies have found that these drugs, when used together, can effectively slow the progression of retinoblastoma, a type of eye cancer, with acceptable side effects.

Topotecan, in particular, has a strong safety record when administered in certain ways, with few serious side effects reported. Carboplatin has also been studied for its safety in ocular use and is considered safe when injected directly into the eye in controlled amounts.

Overall, evidence suggests that the combination of carboplatin and topotecan is a promising and manageable option for treating retinoblastoma, with manageable side effects. However, participants should discuss potential risks and benefits with their healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for retinoblastoma because they combine carboplatin and topotecan in innovative ways to tackle this eye cancer more effectively. Unlike traditional therapies that might primarily rely on surgery or radiation, this approach integrates chemotherapy with focused treatments like cryotherapy and laser photocoagulation, which can be more precise and potentially preserve vision. By exploring different combinations and sequences of these drugs across various stages of retinoblastoma, the trial aims to enhance treatment outcomes, minimize side effects, and better preserve the patient's eyesight.

What evidence suggests that this trial's treatments could be effective for retinoblastoma?

Research has shown that using carboplatin and topotecan together can effectively slow retinoblastoma, a type of eye cancer. In animal studies, this combination outperformed other treatments, such as vincristine with carboplatin. In this trial, some participants will receive carboplatin and topotecan as part of their treatment regimen. Studies have demonstrated that injecting topotecan can quickly reach high levels in the retina, promising for directly targeting the cancer in the eye. Clinical studies also found that using topotecan did not harm the retina or the rest of the body, which is important for safety. This evidence supports the potential of carboplatin and topotecan in treating advanced retinoblastoma and preserving vision. ^{1 2 4 5 6}

Who Is on the Research Team?

Carlos Rodriguez-Galindo, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children with newly diagnosed, untreated intraocular retinoblastoma. It includes those who had unilateral retinoblastoma and now have it in the other eye. They must be able to perform daily activities (ECOG ≤ 2) and have normal kidney and liver function. Those with previous treatments, metastatic disease, active infections or unable to consent are excluded.

Inclusion Criteria

I have been mostly active and able to care for myself in the last two weeks.

I have a new, untreated eye cancer or my other eye has now been affected.

Legal guardians must sign an informed consent indicating that they are aware of this study, the possible benefits, and toxic side effects. Legal guardians will be given a signed copy of the consent form.

Exclusion Criteria

Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

My cancer has spread to other parts of my body or affects my eye socket.

I do not have a serious infection right now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy and focal therapies based on stratification. Treatment includes vincristine, carboplatin, topotecan, etoposide, and focal therapies such as cryotherapy, laser photocoagulation, thermo-therapy, and plaque radiotherapy.

6-8 months

Follow-up

Participants are monitored for ocular survival and event-free survival, with assessments for enucleation and external beam radiation if necessary.

3 years

Exploratory Research

Participants may engage in exploratory research objectives, including cognitive and functional development assessments, pharmacokinetics of topotecan, and evaluation of ototoxicity.

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Enucleation
• External Beam Radiation
• Focal Therapy
• Proton Beam Radiation
• Topotecan

Trial Overview The study tests how well advanced intraocular retinoblastoma responds to direct-eye chemotherapy (carboplatin) plus systemic topotecan. It also uses various therapies like cryotherapy, thermotherapy, radiation therapy, surgery or enucleation if necessary while trying to preserve vision.

How Is the Trial Designed?

Group I: Stratum D Experimental Treatment 9 Interventions

Participants with bilateral retinoblastoma who may require upfront enucleation for one eye due to advanced disease (R-E IV-V and IC E). Interventions (see Detailed Description): vincristine, carboplatin, topotecan, etoposide, enucleation, filgrastim or PEG-filgrastim, focal therapy, including cryotherapy, laser photocoagulation, thermotherapy (and thermo-chemotherapy) and episcleral plaque brachytherapy, and external beam radiation or proton beam radiation in select cases.

Group II: Stratum C Experimental Treatment 9 Interventions

Participants with advanced (R-E IV-V and IC D-E) unilateral retinoblastoma who require upfront enucleation. Participants will be assessed and treated by low, intermediate or high risk. Interventions (see Detailed Description): vincristine, cyclophosphamide, MESNA, doxorubicin, etoposide, carboplatin, filgrastim or PEG-filgrastim, enucleation

Group III: Stratum B Experimental Treatment 7 Interventions

Participants considered candidates for conservative management including those: 1. Participants with bilateral retinoblastoma who have R-E IV-V and IC D in one eye 2. Participants with advanced unilateral (unifocal or multifocal) retinoblastoma (R-E IV-V and IC D-E) who demonstrate foveal sparing by the tumor during EUA. Due to foveal sparing, these patients have potential for vision preservation. Interventions (see Detailed Description): vincristine, topotecan, carboplatin, etoposide, filgrastim or PEG-filgrastim and focal therapy, including cryotherapy, laser photocoagulation, thermo-therapy, plaque radiotherapy.

Group IV: Stratum A Experimental Treatment 6 Interventions

Participants with early bilateral or unilateral (unifocal or multifocal) retinoblastoma (R-E I-III, IC A-B; R-E IV with IC A or B; or IC C with limited sub-retinal seeding), and participants with bilateral disease in whom the advanced eye has been enucleated upfront (without any high risk histopathology) and the remaining eye has early stage disease (as defined above). Interventions (see detailed description): vincristine, carboplatin, topotecan, filgrastim or PEG-filgrastim, and focal therapy, including cryotherapy, laser photocoagulation, thermo-therapy, plaque radiotherapy.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

Intravitreal injection of 90 µg of topotecan resulted in complete regression of recurrent retinal tumors in three children with retinoblastoma, demonstrating its efficacy after prior treatments failed.

The treatment was well-tolerated, with no observed toxicity, marking the first human report of this approach for retinal tumors in retinoblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Topotecan 90 µg for Recurrent Solid Retinoblastoma Tumors Is Effective and Not Toxic. Abramson, DH., Francis, JH.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9792108/

Spotlight on Targeted Chemotherapy in Retinoblastoma According to a rodent study, topotecan with carboplatin effectively stopped the progression of RB compared to vincristine, carboplatin, and ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2162098924000562

Update on chemotherapy modalities for retinoblastoma This review provides a comprehensive update on chemotherapy across various routes, encompassing key considerations, dosages, administration methods, treatment ...

3. ophthalmologyscience.org ophthalmologyscience.org/article/S2666-9145(25)00173-3/fulltext

Suprachoroidal Injection of Topotecan for Retinoblastoma Results. Following a single SCI of 50 μg topotecan, high levels of topotecan were achieved rapidly in both the retina and choroid. Retinal levels peaked by 15 ...

4. jamanetwork.com jamanetwork.com/journals/jamaophthalmology/fullarticle/427366

Intra-arterial Chemotherapy for the Management of ... We showed that IA chemotherapy could be successful in avoiding enucleation in advanced retinoblastoma, with acceptable ocular toxicity and minimal systemic ...

5. retinalphysician.com retinalphysician.com/issues/2024/september/intravitreal-chemotherapy-for-retinoblastoma/

Intravitreal Chemotherapy for Retinoblastoma Clinical studies have shown no retinal or systemic toxicity with 4 weekly injections of topotecan. In a recent phase 1 clinical trial ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8273607/

Ocular safety of repeated intravitreal injections ... To evaluate the ocular safety of intravitreal carboplatin and digoxin injections as a new intravitreal chemotherapy option for retinoblastoma tumor vitreous ...