Intraocular Chemotherapy for Retinoblastoma

Recruiting in Palo Alto (17 mi)

+18 other locations

Overseen by Rachana Shah

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Children's Oncology Group

Disqualifiers: Metastatic spread, Invasive infection, Prior therapy, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial tests the safety and side effects of adding melphalan (by injecting it into the eye) to standard chemotherapy in early treatment of patients with retinoblastoma (RB). RB is a type of cancer that forms in the tissues of the retina (the light-sensitive layers of nerve tissue at the back of the eye). It may be hereditary or nonhereditary (sporadic). RB is considered harder to treat (higher risk) when there are vitreous seeds present. Vitreous seeds are RB tumors in the jelly-like fluid of the eye (called the vitreous humor). The term, risk, refers to the chance of the cancer not responding to treatment or coming back after treatment. Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Other chemotherapy drugs given during this trial include carboplatin, vincristine, and etoposide. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Adding melphalan to standard chemotherapy early in treatment may improve the ability to treat vitreous seeds and may be better than standard chemotherapy alone in treating retinoblastoma.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that patients must not have had any prior anti-cancer therapy other than specific eye treatments. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Melphalan for treating retinoblastoma?

Research shows that Melphalan, especially in its Evomela formulation, is effective for treating retinoblastoma, with improved solubility and stability compared to standard formulations. It has been used successfully in combination with other drugs like carboplatin for managing retinoblastoma, and in some cases, it has helped save the eye from cancer. ^{1 2 3 4 5}

Is intraocular chemotherapy with melphalan safe for humans?

Intraocular chemotherapy with melphalan, used for treating retinoblastoma, has been studied for safety. While it is generally considered safe, some studies report potential eye-related side effects, especially with higher doses or repeated injections, such as retinal toxicity and chorioretinal atrophy (thinning of the retina and choroid). ^{2 4 6 7 8}

How is the drug Melphalan unique in treating retinoblastoma?

Melphalan is unique for retinoblastoma treatment because it is administered directly into the eye (intravitreal injection), allowing it to target the cancer more precisely and potentially reduce side effects compared to systemic treatments (those affecting the whole body). This method is particularly useful for treating recurrent or difficult-to-reach tumors within the eye. ^{1 3 4 6 9}

Research Team

Rachana Shah

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for children under 18 with newly diagnosed retinoblastoma, a cancer of the retina. It's specifically for those with certain types of tumor spread within the eye but no cancer outside it. Kids must have good performance status and adequate organ function, as measured by blood counts and liver/kidney tests.

Inclusion Criteria

I can take care of myself but may not be able to do active work.

Platelet count must be >= 75,000/uL (transfusion independent)

I am under 18 years old.

Exclusion Criteria

Lactating females who plan to breastfeed their infants

I am currently pregnant.

Patients with no reasonable expectation for any useful vision in the Group D eye

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive systemic chemotherapy with carboplatin, vincristine, and etoposide (CVE) for up to 6 cycles, with intravitreal melphalan injections starting from cycle 3 if eligible

24 weeks

Multiple visits for each cycle, including EUA and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Follow-up at 4 weeks, then every 3 months for 1 year, and every 3-6 months for years 2-5

Treatment Details

Interventions

• Melphalan (Alkylating agents)

Trial Overview The study is testing if injecting melphalan into the eye, along with standard chemo drugs like carboplatin, vincristine, and etoposide can better treat retinoblastoma. The focus is on improving treatment for tumors that have spread to the vitreous humor (the jelly-like fluid inside the eye).

Participant Groups

Group I: Treatment (CVE, melphalan) Experimental Treatment 8 Interventions

See Detailed Description

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Dr. Doug Hawkins

Children's Oncology Group

Chief Executive Officer since 2020

MD from University of Washington School of Medicine

Dr. Leo Mascarenhas

Children's Oncology Group

Chief Medical Officer since 2024

MD, MS from Cedars-Sinai Guerin Children’s

Findings from Research

In a study of 22 retinoblastoma patients treated with intravitreal carboplatin and melphalan, 77% of primary cases and 89% of refractory cases achieved complete control of vitreous seeds after 6 months, indicating the treatment's efficacy.

The treatment was associated with a low incidence of serious side effects, with no cases of orbital invasion, systemic metastasis, or death, suggesting it is a relatively safe option for managing vitreous seeds in retinoblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of intravitreal carboplatin with melphalan for management of vitreous seeding in retinoblastoma. Riazi-Esfahani, H., Masoomian, B., Khodabandeh, A., et al.[2023]

A 12-month-old boy with recurrent retinoblastoma successfully retained his functional eye after receiving combined intravitreal and intracameral injections of melphalan, demonstrating the treatment's efficacy.

After 3 years of follow-up, the patient showed no signs of disease recurrence, indicating that this method of administering melphalan can effectively manage retinoblastoma in the anterior chamber.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eye Salvage with Combination of Intravitreal and Intracameral Melphalan Injection for Recurrent Retinoblastoma with Anterior Chamber Involvement: Report of a Case. Cassoux, N., Aerts, I., Lumbroso-Le Rouic, L., et al.[2023]

Intravitreal melphalan (IVM) treatment for vitreous seeding in retinoblastoma patients showed an 83.3% enucleation-free survival rate, indicating its efficacy in managing this condition.

However, the treatment was associated with significant ocular toxicities, including retinal pigment epithelium atrophy and pupillary synechiae, affecting a majority of patients, which highlights the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular toxicity of intravitreal melphalan for retinoblastoma in Chinese patients. Xue, K., Ren, H., Meng, F., et al.[2020]

Intravitreal melphalan injections (30 μg weekly) in retinoblastoma patients led to a decrease in retinal function, as indicated by a reduction in electroretinogram (ERG) amplitudes, suggesting retinal toxicity with continued treatment.

Despite the observed retinal toxicity, no significant systemic toxicity was detected in either the human patients or the rabbit model, indicating that while melphalan affects retinal health, it may be safe for systemic use at these doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study. Francis, JH., Schaiquevich, P., Buitrago, E., et al.[2022]

A case study of a 12-month-old girl with retinoblastoma showed that a single low-dose intravitreal melphalan injection led to diffuse chorioretinal atrophy at the injection site, indicating potential retinal toxicity even at standard doses.

Despite the resolution of the main tumor and vitreous seeds after treatment, the patient experienced persistent retinal pigment epithelium alterations and hard exudates for over two years, highlighting the need for careful monitoring of patients receiving intravitreal melphalan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffuse chorioretinal atrophy after a single standard low- dose intravitreal melphalan injection in a child with retinoblastoma: a case report. Chao, A., Kao, LY., Liu, L., et al.[2022]

Intravitreal injection of melphalan for retinoblastoma is a safe treatment, with a low risk of serious adverse events; only one case of a postoperative subconjunctival tumor was reported, and no infections or uveitis occurred.

The treatment was effective, achieving complete vitreous seed remission in 68% of eyes, with about half of those maintaining good visual acuity, indicating that melphalan can be a viable option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal injection of melphalan for intraocular retinoblastoma. Suzuki, S., Aihara, Y., Fujiwara, M., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Addition of intravitreal carboplatin with melphalan for management of vitreous seeding in retinoblastoma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy of a prolonged stability melphalan formulation for intra-arterial treatment of retinoblastoma. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Eye Salvage with Combination of Intravitreal and Intracameral Melphalan Injection for Recurrent Retinoblastoma with Anterior Chamber Involvement: Report of a Case. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and toxicity of intravitreal melphalan formulations for retinoblastoma. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Evaluation of intravitreal topotecan dose levels, toxicity and efficacy for retinoblastoma vitreous seeds: a preclinical and clinical study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Ocular toxicity of intravitreal melphalan for retinoblastoma in Chinese patients. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Diffuse chorioretinal atrophy after a single standard low- dose intravitreal melphalan injection in a child with retinoblastoma: a case report. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

Intravitreal injection of melphalan for intraocular retinoblastoma. [2022]