Intra-arterial Chemotherapy for Retinoblastoma

(IAC Trial)

Overseen By Margaret Reynolds, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: Opaque media, Systemic chemotherapy, Metastatic sites, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

5 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are currently receiving any other investigational agents, you may not be eligible to participate.

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

Research shows that using Melphalan in intra-arterial chemotherapy (directly into the artery) has been effective in treating retinoblastoma, leading to tumor shrinkage and saving the eye in some cases. ^{1 2 3 4 5}

What makes intra-arterial melphalan unique for treating retinoblastoma?

Intra-arterial melphalan is unique because it delivers chemotherapy directly to the eye's blood vessels, allowing for higher concentrations of the drug to target the tumor with potentially fewer side effects compared to traditional systemic chemotherapy (treatment that affects the whole body). ^{2 3 4 5 6}

What is the purpose of this trial?

Children with retinoblastoma who may benefit from intra-arterial chemotherapy will receive up to 3 doses of melphalan and will be assessed for feasibility, toxicity, and response.

Research Team

Margaret Reynolds, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for children over 4 months old with retinoblastoma, a type of eye cancer. It's specifically for those who haven't responded to systemic chemotherapy and are facing limited treatment options like eye removal or radiation. Patients need consent from a parent or guardian. Those with allergies to melphalan, pregnant/breastfeeding individuals, HIV patients with low CD4+ counts or recent opportunistic infections, and cases where the cancer has spread significantly are excluded.

Inclusion Criteria

My next treatment options include chemotherapy, radiotherapy, or eye removal.

Other patients may be considered on a case by case basis after discussion with pediatric ophthalmology, hematology/oncology, and interventional neuroradiology.

Patient or parent/legal guardian must sign a written informed consent

Exclusion Criteria

I do not have any uncontrolled illnesses or heart problems.

A history of allergic reactions attributed to compounds of similar composition to melphalan or other study agents

Currently receiving any other investigational agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intra-arterial injections of melphalan every 4 weeks for 3 cycles

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Melphalan

Trial Overview The trial tests intra-arterial chemotherapy using melphalan in children with retinoblastoma. Participants will receive up to three doses of this drug directly into the artery supplying the eye tumor. The study aims to evaluate how feasible and toxic this approach is and how well it works in shrinking the tumors.

Participant Groups

Group I: Intra-arterial injections of melphalan Experimental Treatment 1 Intervention

-Participants will receive intra-arterial injections of melphalan Q4W for 3 cycles.

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

Approved in European Union as Alkeran for:

• Multiple myeloma
• Malignant lymphoma
• Acute lymphoblastic leukemia
• Acute myeloblastic leukemia
• Childhood neuroblastoma
• Ovarian cancer
• Mammary adenocarcinoma

Approved in United States as Alkeran for:

• Multiple myeloma
• High-dose conditioning before hematopoietic stem cell transplant
• Uveal melanoma with unresectable hepatic metastases

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

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]

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

Three-drug intra-arterial chemotherapy using simultaneous carboplatin, topotecan and melphalan for intraocular retinoblastoma: preliminary results. [2022]

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

Two-dose exposure of intra-arterial chemotherapy for group D retinoblastoma. [2016]

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

The Addition of Topotecan to Melphalan in the Treatment of Retinoblastoma with Intra-arterial Chemotherapy. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Superselective intra-arterial melphalan therapy for newly diagnosed and refractory retinoblastoma: results from a single institution. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Intra-Arterial Chemotherapy for Retinoblastoma: A Single-Center Experience. [2015]