A Study to Give Treatment Inside the Eye to Treat Retinoblastoma
Start Date
11/4/2022
Completion Date
3/31/2028
Summary
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.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the feasibility of administering intravitreal melphalan by cycle 6 when given in combination with systemic carboplatin, vincristine, and etoposide (CVE) for the treatment of Group D retinoblastoma with vitreous seeding. SECONDARY OBJECTIVES: I. To determine the safety and toxicity profile associated with intravitreal melphalan in combination with systemic CVE for the treatment of Group D retinoblastoma with vitreous seeding. II. To evaluate the efficacy of intravitreal melphalan in conjunction with systemic chemotherapy in Group D intraocular retinoblastoma with vitreous seeding. EXPLORATORY OBJECTIVES: I. To determine if eyes that become eligible for injection at cycle 3 or later would have been eligible for injection at diagnosis by retrospective central review of examination under anesthesia (EUA) and ultrasound biomicroscopy (UBM) images from diagnosis. II. To validate and standardize the extraction, storage and collection protocols across multiple centers to demonstrate that aqueous humor from eyes undergoing therapy have high enough tumor-derived deoxyribonucleic acid (DNA) concentration for whole genome sequencing and RB1 testing. III. To explore the relationship between highly-recurrent retinoblastoma (RB) somatic copy number alterations (SCNAs) and ocular salvage as well as tumor fraction (% of tumor DNA) as a marker of minimal residual disease and risk of intraocular disease relapse. IV. To evaluate the effects of intravitreal melphalan therapy in the histopathology of enucleated eyes for progressive or recalcitrant retinoblastoma while on therapy. V. To evaluate the long-term visual potential of eyes salvaged using intravitreal therapy. OUTLINE: CYCLES 1-2: Patients receive CVE regimen consisting of: carboplatin intravenously (IV) over 15-60 minutes on days 1 and 2 of each cycle, vincristine IV on day 1 of each cycle, and etoposide IV over 90-120 minutes on day 1 and 2 of each cycle. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ultrasound biomicroscopy (UBM) and imaging of the eye during a procedure called examination under anesthesia (EUA) at baseline and prior to each cycle, and urine sample collection at baseline and on study. NOTE: UBM is completed prior to cycle 1 only. CYCLES 3+: Patients receive CVE regimen as in cycles 1-2. Patients also undergo EUA prior to each cycle to determine eligibility to receive melphalan. If found eligible, patients receive intravitreal injection of melphalan once between days -14 to 14 of each cycle. Patients who are not eligible for melphalan for any cycle receive CVE only regimen for that cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo urine sample collection at baseline and on study for Cycles 3-6. NOTE: Patients may be eligible to receive additional cycles of melphalan alone (maximum of 6 injections). Additionally, patients undergo magnetic resonance imaging and may undergo aqueous humor and tissue sample collection throughout the trial. After completion of study treatment, patients are followed up at 4 weeks, then every 3 months for 1 year, and then every 3-6 months for years 2-5.
Eligibility Criteria
Age Range: No minimum to 18 years
Interventions
Biospecimen Collection
Carboplatin
Etoposide
Examination Under Anesthesia
Magnetic Resonance Imaging
Melphalan
Ultrasound Biomicroscopy
Vincristine
Conditions
Locations
Children's Hospital of Alabama
Birmingham, Alabama 35233
United States
Children's Hospital Los Angeles
Los Angeles, California 90027
United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California 94304
United States
Children's Hospital Colorado
Aurora, Colorado 80045
United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia 30329
United States
C S Mott Children's Hospital
Ann Arbor, Michigan 48109
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Duke University Medical Center
Durham, North Carolina 27710
United States
Children's Hospital Medical Center of Akron
Akron, Ohio 44308
United States
Cleveland Clinic Foundation
Cleveland, Ohio 44195
United States
Saint Jude Children's Research Hospital
Memphis, Tennessee 38105
United States
Dell Children's Medical Center of Central Texas
Austin, Texas 78723
United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas 75390
United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas 77030
United States
M D Anderson Cancer Center
Houston, Texas 77030
United States
Primary Children's Hospital
Salt Lake City, Utah 84113
United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin 53226
United States
Royal Children's Hospital
Parkville, Victoria 3052
Australia
Perth Children's Hospital
Perth, Western Australia 6009
Australia
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec H3T 1C5
Canada