Unilateral Retinoblastoma
Conditions
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.
Interventions
DRUGMelphalan
Given IA
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Melphalan Patients receive melphalan intra-arterial (IA) on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Melphalan: Given IA | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Non-Protocol Therapy | 1 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Progressive Disease | 3 |
| Overall Study | Refusal of Further Protocol Therapy | 1 |
Baseline characteristics
| Characteristic | Melphalan |
|---|---|
| Age, Continuous | 1.92 years STANDARD_DEVIATION 0.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 3 / 14 |
| serious Total, serious adverse events | 2 / 14 |
Outcome results
Primary
Number of Patients Experiencing Feasibility Failure
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.
Time frame: Up to 4 months
Population: All Patients who are eligible and evaluable for the feasibility outcome are included in this outcome
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan | Number of Patients Experiencing Feasibility Failure | 4 participants |
Secondary
Incidence of Grade 3 or Higher CTCAE Adverse Events Associated With Multiple Doses of IA Chemotherapy
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.
Time frame: Up to 30 days after completion of study treatment
Population: One patient who did not receive protocol therapy was excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan | Incidence of Grade 3 or Higher CTCAE Adverse Events Associated With Multiple Doses of IA Chemotherapy | 38 Percentage of patients |
Secondary
Probability of Ocular Salvage
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.
Time frame: 2 years
Population: One patient who did not receive protocol therapy was excluded. Two patients who were lost to follow-up or follow-up was terminated electively prior to 2 years by patient or parent preference were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan | Probability of Ocular Salvage | 36 Percentage of patients |
Secondary
Rate of Metastases of Retinoblastoma
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
Time frame: Up to 2 years
Population: One patient who did not receive protocol therapy was excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan | Rate of Metastases of Retinoblastoma | 0 Percentage of Patients |
Secondary
Vision Acuity, Assessed According to the Amblyopia Treatment Study Visual Acuity Testing Protocol
Estimated by the average visual acuity amongst patients evaluated with a 95% confidence interval.
Time frame: 1 year after therapy
Population: The study was terminated at stage I since the therapy was considered not feasible to deliver.~No patients had this data available. Patients either had affected eye enucleated, or did not complete protocol therapy.