Intra-arterial Chemotherapy for Retinoblastoma

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
Intra-arterial Chemotherapy for Retinoblastoma (IAC)

Conditions
-----------------
Retinoblastoma

Intervention / Treatment
-----------------
* Drug: Melphalan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients diagnosed with retinoblastoma >4 months of age16 Patients whose other treatment options would require systemic chemotherapy, radiotherapy, or enucleation Patient or parent/legal guardian must sign a written informed consent One of a, b, or c: Patients who have bilateral COG stage B, C, D, or E retinoblastoma (refer to Appendix A) who have undergone systemic chemotherapy without resolution (meaning either has not had CR or has progressed despite systemic chemotherapy) and would have the following treatment options remaining: IAC enucleation of one eye local radiation Patients with non-germline retinoblastoma with unilateral disease who have COG A, B, C, or D tumors (refer to Appendix A). Other patients may be considered on a case by case basis after discussion with pediatric ophthalmology, hematology/oncology, and interventional neuroradiology. Exclusion Criteria: Opaque or hazy media which precluded visualization of the fundus. New or recurrent retinoblastoma that can be controlled with other conservative measures such as cryotherapy, thermotherapy, or plaque radiotherapy. Unilateral COG group E retinoblastoma (refer to Appendix A) with very poor visual prognosis as defined by pediatric ophthalmologist. Patients who would benefit from systemic chemotherapy. Patients with clinical or radiological evidence suggestive of retinoblastoma invasion of the optic nerve, choroid, sclera, orbit or metastatic sites. Currently receiving any other investigational agents. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan or other agents used in the study. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Pregnant and/or breastfeeding. Participants of childbearing potential must have a negative pregnancy test within 14 days of study entry. Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.

Ages Eligible for Study
-----------------
Minimum Age: 4 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intra-arterial injections of melphalan<br>-Participants will receive intra-arterial injections of melphalan Q4W for 3 cycles. | Drug: Melphalan<br>* -The drug is commerically available<br>* Other names: Evomela;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of intra-arterial chemotherapy as measured by the number of participants who receive 3 intra-arterial injections of melphalan | -Feasibility is defined as the ability to receive 3 intra-arterial injections of melphalan per patient. | Completion of enrollment and treatment of all patients (estimated to be 32 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of procedure-related complications |  | Through 30 days following completion of treatment (estimated to be 4 months) | 
| Rate of ocular salvage | A patient will be considered a successful ocular salvage if the child does not experience enucleation because of disease progression or toxicity during 2 years of follow-up. | 2 years post-treatment | 
| Visual acuity as measured by Cardiff testing |  | 6 months post-treatment | 
| Rate of metastatic disease | -Patients will be determined to have metastatic disease if they have received 1 or more administrations of IAC and they are found to have progression of disease or appearance of tumor outside of the eye after protocol therapy. Pineal tumors will not be considered metastatic disease. | Completion of treatment (estimated to be 3 months) |