Intra-arterial Melphalan in Treating Younger Patients With Unilateral Retinoblastoma

Phase 1

Completed

Brief Summary: This pilot clinical trial studies whether unilateral group D retinoblastoma, or retinoblastoma affecting one eye that has spread to the inner jelly like part of the eye, can be treated with a new technique for delivering chemotherapy directly into the blood vessel that supplies the affected eye. This new technique is called intra-arterial injection. Giving melphalan via intra-arterial injection may make it less likely that children will need surgery to remove the eye and may reduce the amount of treatment side effects.

Detailed Description: PRIMARY OBJECTIVES:

I. To study the feasibility of delivering melphalan directly into the ophthalmic artery in children with newly diagnosed unilateral group D retinoblastoma, who would otherwise be considered for enucleation.

SECONDARY OBJECTIVES:

I. To estimate the ocular salvage rate after treatment with intra-arterial melphalan in children with newly diagnosed unilateral retinoblastoma with group D disease.

II. To evaluate the toxicities and adverse events associated with delivering multiple doses of intra-arterial chemotherapy.

III. To evaluate vision outcomes in children treated with intra-arterial chemotherapy.

IV. To monitor the rate of the development of metastatic disease while on protocol therapy.

TERTIARY OBJECTIVES:

I. To evaluate the effects of intra-arterial therapy on the histopathology of eyes enucleated for progression.

OUTLINE:

Patients receive melphalan intra-arterially (IA) on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then periodically for 2 years.

Recruitment & Eligibility

Inclusion Criteria

Newly diagnosed patients with unilateral group D retinoblastoma
Magnetic resonance imaging (MRI) (or computed tomography [CT] if MRI is not available) of the brain must be performed within 14 days prior to study entry
Diagnostic examination under anesthesia (EUA) must be performed within 14 days prior to study entry
Rapid central review confirmation of group D disease based on RetCam images from diagnostic EUA must be obtained before starting treatment
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2
Patients must have a life expectancy of >= 8 weeks
Patients must have adequate renal function, defined as:
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or
- A serum creatinine based on age/gender as follows:
  - 1 month to < 6 months: 0.4 mg/dL
  - 6 months to < 1 year: 0.5 mg/dL
  - 1 to < 2 years: 0.6 mg/dL
  - 2 to < 6 years: 0.8 mg/dL
  - 6 to < 10 years: 1 mg/dL
  - 10 to < 13 years: 1.2 mg/dL
  - 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
  - >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age

Exclusion Criteria

Patients with bilateral disease
Unilateral retinoblastoma with group A, B, C, or E eyes
Prior chemotherapy or radiation therapy for this disease (laser and cryotherapy are allowed and are not considered exclusion criteria)
Clinical or neuroimaging evidence of extraocular disease or orbital optic nerve involvement

Arm && Interventions

Group	Intervention	Description
Treatment (melphalan)	Melphalan	Patients receive melphalan IA on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Number of Patients Experiencing Feasibility Failure	Up to 4 months	Feasibility failure is defined as a) interventional radiologist is unable to access the ophthalmic artery for the 1st chemotherapy administration for any reason; b) patient develops central retinal artery occlusion after the 1st or 2nd course that does not reopen by the time the next injection is due; or c) the patient cannot receive all three treatments because of Common Terminology Criteria for Adverse Events (CTCAE) complications grade III or IV that are considered possibly, probably or likely related treatment.

Secondary Outcome Measures

Name	Time	Method
Incidence of Grade 3 or Higher CTCAE Adverse Events Associated With Multiple Doses of IA Chemotherapy	Up to 30 days after completion of study treatment	The percentage of patients with at least 1 occurrence of grade 3 or higher CTCAE adverse experience will be provided. Ineligible patients or patients who do not receive any protocol therapy are excluded from reporting of adverse events.
Probability of Ocular Salvage	2 years	A patient will be considered an ocular-salvage success if enucleation because of disease progression or toxicity is not required during the 2 years following enrollment.
Rate of Metastases of Retinoblastoma	Up to 2 years	The percentage of patients who experience metastases of retinoblastoma will be estimated. Ineligible patients or patients who do not receive any protocol therapy are excluded from this analysis
Vision Acuity, Assessed According to the Amblyopia Treatment Study Visual Acuity Testing Protocol	1 year after therapy	Estimated by the average visual acuity amongst patients evaluated with a 95% confidence interval.

Locations (12): UCSF Medical Center-Mission Bay
🇺🇸
San Francisco, California, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸
Houston, Texas, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States