Individualized Therapy for Retinoblastoma

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Metastatic disease, Orbital involvement, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how personalized treatments can effectively manage retinoblastoma, a type of childhood eye cancer. Researchers will categorize participants based on whether one or both eyes are affected and the cancer's stage. They will test various therapies, including chemotherapy (using drugs like Carboplatin, Doxorubicin, Etoposide, and Vincristine), surgery, and targeted treatments like laser therapy. A key focus is to observe how advanced tumors respond to a new chemotherapy combination and to study how children adapt to vision changes. Children with newly diagnosed retinoblastoma, especially those whose cancer hasn't spread or been treated yet, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 treatments under study for retinoblastoma are generally well-tolerated. Studies on the combination of vincristine and topotecan have found this mix effective in treating advanced retinoblastoma in both eyes, with manageable side effects. While some side effects may occur, they are not severe and can be controlled.

For those receiving vincristine and carboplatin, this treatment is commonly used and is known to cause side effects like myelosuppression, which decreases bone marrow activity and leads to fewer blood cells. This can increase infection risk, but it is a known and manageable risk.

The combination of vincristine, carboplatin, and etoposide has also been used and follow-up studies have shown no cancer spread, suggesting the treatment is effective and relatively safe over time.

Lastly, vincristine, cyclophosphamide, and doxorubicin are used for high-risk patients. This combination is safe and effective at reducing the chances of cancer spreading after surgery.

In summary, while these treatments have some side effects, they are generally expected and manageable with proper care. Safety data from these studies suggest they are suitable for treating retinoblastoma in children. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the individualized therapy for retinoblastoma because it tailors treatment to the specific stage and risk level of the disease, unlike the one-size-fits-all approach of current treatments. For early-stage cases, the combination of vincristine and carboplatin, coupled with focal therapies, offers targeted intervention with potentially fewer side effects. In more advanced stages, the treatment alternates between chemotherapy regimens, including vincristine, etoposide, and doxorubicin, maximizing effectiveness based on individual tumor response. This personalized approach not only aims to improve outcomes but also minimizes unnecessary treatments, aligning with the latest trend towards precision medicine.

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

Research has shown that using vincristine and carboplatin together, as studied in Stratum A of this trial, can effectively treat retinoblastoma by reducing the need for more invasive treatments like radiation or eye removal. Studies have found that this combination can delay or even prevent these interventions. In Stratum B, for more advanced cases, the combination of vincristine and topotecan has effectively managed advanced retinoblastoma in both eyes with manageable side effects. Another successful option in Stratum C involves using vincristine, carboplatin, and etoposide together, which has helped prevent the cancer from spreading after eye removal. Additionally, the combination of vincristine, cyclophosphamide, and doxorubicin, also part of Stratum C, has been studied for high-risk cases and has improved survival rates. These treatments offer promising ways to tackle retinoblastoma while aiming to save both vision and life. ^{3 6 7 8 9}

Who Is on the Research Team?

Ibrahim Qaddoumi, M.D.

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children with newly diagnosed retinoblastoma, a type of eye cancer. They must have good liver and kidney function, be expected to live at least 8 weeks, and have a performance status showing they can do some daily activities. Kids who've had surgery or focal treatments on one eye but then get cancer in the other are also eligible. Children with spread of cancer outside the eye or an active infection cannot join.

Inclusion Criteria

I have a new diagnosis of eye cancer and haven't been treated, or I had treatment for cancer in one eye and now the other is affected.

Must have a life expectancy of at least 8 weeks.

I am able to get out of my bed or chair and move around.

Exclusion Criteria

I do not have a serious infection right now.

Patients who have received treatment for this condition before.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive individualized treatment based on the form and stage of retinoblastoma, including chemotherapy, surgery, and focal treatments.

6-12 months

Regular visits for chemotherapy cycles and focal treatments

Follow-up

Participants are monitored for ocular survival and event-free survival, as well as cognitive and developmental assessments.

5 years

Annual visits for assessments and monitoring

Long-term Follow-up

Participants are monitored for changes in visual cortex function and development of pineal cysts.

6 years after last patient enrollment

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Doxorubicin
• Enucleation
• Etoposide
• External Beam Radiation
• Focal Therapies
• G-CSF
• Periocular carboplatin
• Vincristine
• Vincristine and Carboplatin
• Vincristine and Topotecan
• Vincristine, Carboplatin and Etoposide

Trial Overview The study tests various treatments based on whether one or both eyes are affected and how advanced the disease is. It includes chemotherapy combinations like topotecan and vincristine (with G-CSF support), carboplatin around the eye, plus potential surgeries and focal therapies like laser treatment. The aim is to cure cancer, save vision, understand how kids adapt visually post-treatment, and learn more about retinoblastoma biology.

How Is the Trial Designed?

Group I: Stratum C Experimental Treatment 5 Interventions

Patients with advanced unilateral advanced intraocular disease. First intervention is enucleation. If enucleated eye does not have disease outside the retina (low risk), no additional treatment is given. For patients whose enucleated eye shows tumor outside the retina (intermediate risk), they will receive 4 courses of vincristine, cyclophosphamide, and doxorubicin followed by G-CSF. For patients with high risk disease (involvement of the sclera, optic nerve at the level of the cut-end), treatment after enucleation is 6 courses of alternating chemotherapy with vincristine, carboplatin, etoposide (VCE) to alternate with vincristine, cyclophosphamide, and doxorubicin (VCD). High risk patients also receive external-beam radiation therapy.

Group II: Stratum B Experimental Treatment 8 Interventions

Patients with bilateral disease (at least one advanced stage eye), candidate for conservative management. Treatment included window treatment with vincristine and topotecan, Followed by 3 more courses of vincristine-topotecan if they had a response to the window+ 6 courses of vincristine and carboplatin. If they do not respond to the window, they receive 6 courses of vincristine, carboplatin, and etoposide. Periocular carboplatin is also given three times, depending on whether they respond to window. External Beam Radiation 44-46 Gy administered using standard practices.

Group III: Stratum A Experimental Treatment 5 Interventions

Patients with early bilateral or unilateral, or patients with bilateral that have already had the advanced eye enucleated. Treatment included vincristine and carboplatin for 8 courses, given at 3-4 week intervals. Focal therapies any time after second course can include cryotherapy, laser photocoagulation, thermotherapy, and 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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/12743157/

Treatment of intraocular retinoblastoma with vincristine and ... To evaluate the efficacy of chemoreduction using vincristine and carboplatin in preventing or delaying external-beam radiotherapy (EBRT) or enucleation.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1319453413000738

Efficacy of vincristine and carboplatin as chemo-reduction ... In a study by Friedman27, 47 patients were treated with 6 cycles of vincristine, etoposide and carboplatin along with focal therapy in the majority of patients ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.10002

Vincristine and topotecan versus carboplatin-, etoposide ... We did a randomised comparative trial in children with group D/E intraocular retinoblastoma (IORB) to compare 2 different chemotherapy regimens.

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2825162

Three vs 6 Cycles of Chemotherapy for High-Risk ... 3 cycles of CEV chemotherapy resulted in 5-year disease-free survival that was noninferior to 6 cycles of CEV chemotherapy.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00002794?tab=table

Carboplatin Plus Vincristine in Treating Children With ... A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00002794

Carboplatin Plus Vincristine in Treating Children With ... Estimate the objective response rate in infants and children with retinoblastoma when treated with carboplatin (CBDCA) and vincristine (VCR) ...

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

Ocular safety of repeated intravitreal injections ... In this experimental study, we investigated the ocular safety of repeated intravitreal injections of 1 µg/0.1 cc Carboplatin and 10 µg/0.1 cc Digoxin as an ...

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

Update on chemotherapy modalities for retinoblastoma In 2006, Shields et al. reported on a large cohort of 249 cases treated with intravenous vincristine, etoposide, and carboplatin (VEC). They achieved globe ...

9. jamanetwork.com jamanetwork.com/journals/jamaophthalmology/fullarticle/413027

Complications of Systemic Chemotherapy as Treatment ... Systemic chemotherapy employed for retinoblastoma has been associated with adverse events such as myelosuppression and subsequent infections and need for ...