Intra-arterial Chemotherapy for Retinoblastoma

(IAC Trial)

No longer recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests melphalan for children with retinoblastoma, a type of eye cancer. The goal is to determine if administering melphalan directly into the arteries can be a safe and effective option, especially for those who haven't responded to other treatments. It offers an alternative for children who might otherwise require more aggressive treatments like full-body chemotherapy or eye removal. Children with retinoblastoma who have not succeeded with other treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, giving participants the chance to be among the first to receive this potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that melphalan, administered directly into the arteries (known as intra-arterial chemotherapy), is generally well-tolerated in children with retinoblastoma. One study followed 357 eyes treated with melphalan and found that most patients managed it well over several treatments. Another review identified this method as an effective and safe option for treating retinoblastoma. Although some side effects may occur, evidence suggests the treatment is safe enough for use in children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about intra-arterial chemotherapy with melphalan for retinoblastoma because it offers a targeted delivery method that directly reaches the tumor. Unlike traditional treatments like systemic chemotherapy or external beam radiation, this approach delivers the drug directly into the arteries feeding the cancer, potentially increasing effectiveness while reducing side effects. Melphalan, the active ingredient in this treatment, is specifically chosen for its potent ability to kill cancer cells. This method could mean fewer systemic side effects and better preservation of vision for patients, which is a significant advantage over more generalized treatments.

What evidence suggests that intra-arterial chemotherapy with melphalan might be an effective treatment for retinoblastoma?

Research has shown that delivering the chemotherapy drug melphalan directly to the eye can effectively treat retinoblastoma, a type of eye cancer in children. One study found that this method saved the affected eye in about 55% of cases. Participants in this trial will receive intra-arterial injections of melphalan, which target the eye directly and may reduce side effects compared to traditional chemotherapy. Another study found that using melphalan in this way offers acceptable effectiveness for patients. While results can vary, especially in more advanced cases, the treatment has shown promise in controlling the disease. ^{2 3 6 7 8}

Who Is on the Research Team?

Margaret Reynolds, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40563605/

Intra-Arterial Melphalan Chemotherapy for Retinoblastoma ... IAC achieves long-term globe salvage in 55% of Rb cases; however, outcomes are poorer with Group D/E tumors, vitreous seeds, prior IVC failure, or requiring >3 ...

2. ophthalmologyretina.org ophthalmologyretina.org/article/S2468-6530(25)00065-X/fulltext

Intra-arterial Chemotherapy for Retinoblastoma, Outcomes ... A total of 357 eyes were treated with 1536 IAC infusions, with a median of 4 cycles per eye, and followed for 60.69 months.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8860512/

The Safety and Effectiveness of Melphalan-Based Intra ... Our meta-analysis showed that melphalan-based IAC treatment was an option for retinoblastoma patients with acceptable efficacy according to retrospective ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01293539?intr=EVOMELA&aggFilters=studyType:int&viewType=Table&rank=9

Intra-arterial Chemotherapy for the Treatment of Intraocular ... A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology ...

5. jamanetwork.com jamanetwork.com/journals/jamaophthalmology/fullarticle/1106475

Intra-arterial Chemotherapy for Retinoblastoma The possible benefits of IAC include reduced dose of chemotherapy into the ophthalmic artery, thus minimizing systemic dose and toxic effects to the remainder ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12190955/

Intra-Arterial Melphalan Chemotherapy for Retinoblastoma in ... Data collection included patients' demographics, tumor staging, eye salvage, complications, and survival, followed by statistical comparisons ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02116959

Alternating Systemic Chemotherapy and Intra-Arterial ... The purpose of this study is to test the safety of the treatment combination of alternating standard chemotherapy and another (melphalan) chemotherapy at ...

8. ajnr.org ajnr.org/content/41/7/1286

Intra-Arterial Chemotherapy for Retinoblastoma in Infants ... We herein describe our efficacy and safety outcomes in a large series of IAC infusions performed in infants weighing ≤10 kg. MATERIALS AND ...