Intraocular Retinoblastoma
Conditions
Brief summary
This phase III trial is studying how well giving carboplatin and vincristine together with standard local ophthalmic therapy works in treating children with intraocular retinoblastoma. Drugs used in chemotherapy, such as carboplatin and vincristine, work in different ways to stop tumor from dividing so they stop growing or die. It is not yet known whether neoadjuvant chemotherapy combined with standard local ophthalmic therapy is effective in treating intraocular retinoblastoma.
Detailed description
PRIMARY OBJECTIVES: I. Determine the 2-year event-free survival of patients with Group B intraocular retinoblastoma treated with neoadjuvant chemoreduction comprising carboplatin and vincristine and standardized local ophthalmic therapy. SECONDARY OBJECTIVES: I. Determine the response rate after one course of chemoreduction (before standardized local ophthalmic therapy) in these patients. II. Correlate response rate with event-free survival in patients treated with this regimen. III. Determine the incidence of toxic effects in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive chemoreduction comprising carboplatin IV over 60 minutes followed by vincristine IV over 1-2 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the first course of chemoreduction, patients undergo standardized local ophthalmic therapy comprising local laser therapy, cryotherapy, and/or radioactive plaque comprising iodine I 125 or ruthenium Ru 106. Patients are followed every 3-4 weeks until there is no active tumor seen on a minimum of 3 ophthalmic exams under anesthesia, every 6-8 weeks until 3 years of age, every 4-6 months until 10 years of age, and then annually thereafter.
Interventions
DRUGCarboplatin
Given IV
PROCEDURECryosurgery
PROCEDUREInfrared Laser Therapy
RADIATIONIodine I-125
Undergo radioactive therapy
RADIATIONRadiation Therapy
Undergo radioactive therapy
RADIATIONRuthenium Ru-106
Undergo radioactive therapy
DRUGVincristine Sulfate
Given IV
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
No minimum to 5 Years
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed Group B intraocular retinoblastoma meeting 1 of the following criteria: * Group B tumor(s) in 1 eye * Group B tumor(s) in both eyes * Group A tumor in 1 eye and Group B tumor(s) in the other eye * Group E tumor in 1 eye that has been enucleated and Group B tumor(s) in the remaining eye at the time of enucleation of the Group E tumor * Defined by the International Classification System for Intraocular Retinoblastoma as follows: * Group A: Small tumors (≤ 3 mm in greatest dimension) confined to the retina, away from foveola and disc meeting the following criteria: * More than 3 mm from fovea * More than 1.5 mm from optic disk * Group B: Tumors more than 3 mm meeting the following criteria: * Confined to the retina in any location not in Group A * Tumor associated subretinal fluid \< 3 mm from the tumor margin with no subretinal seeding * Group E: Must have ≥ 1 of the following present: * Tumor touching the lens * Tumor anterior to anterior vitreous face involving ciliary body or anterior segment * Diffuse infiltrating retinoblastoma * Neovascular glaucoma * Opaque media from hemorrhage * Tumor necrosis with aseptic orbital cellulites * Phthisis bulbi * Confirmation of diagnosis by CT scan or MRI of the brain and orbits AND an ophthalmologic evaluation under anesthesia within the past 3 weeks * No choroidal and/or optic nerve invasion past the lamina cribosa * No evidence of extraocular retinoblastoma clinically or by head and orbital MRI and/or CT scan * No tumor present on histological exam at the cut end of the optic nerve for any Group E eye enucleated before study entry * Performance status - ECOG 0-2 * Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age * AST or ALT \< 2.5 times ULN for age * Creatinine clearance (based on Schwartz formula) or radioisotope glomerular filtration rate ≥ 70mL/min/1.73 m\^2 * No prior chemotherapy * No other concurrent chemotherapy * No prior radiotherapy * No other concurrent radiotherapy, including intensity-modulated stereotactic, or proton beam radiotherapy * Prior enucleation of one eye allowed provided the remaining eye is Group B * No concurrent enucleation * No prior local ophthalmic therapy for retinoblastoma * No other prior therapy for retinoblastoma * No local therapy during chemotherapy course 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival | At 2 years | Proportion of patients with event free survival at 2 years. An event is defined as the need for non-protocol therapy, defined as additional on-protocol chemotherapy, enucleation or external beam radiation, among patients with Group B intraocular tumors with a schedule of neoadjuvant 2-agent (Vincristine/Carboplatin) chemotherapy (chemo-reduction) and standardized local ophthalmic therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (RR) at Patient Level After the First Course of Therapy | 1 month after enrollment | RR will be estimated. The response after 1 course of chemotherapy will be used to better define response to this neoadjuvant systemic chemotherapy, prior to the use of local ophthalmic therapy. Response to subsequent courses will help define response to combined systemic chemotherapy and local ophthalmic therapy. Number of patients with Type I, II, III or IV response after first course of therapy |
| Response Rate (RR) at Eye Levels After the First Course of Therapy | 1 month after enrollment | RR will be estimated. The response after 1 course of chemotherapy will be used to better define response to this neoadjuvant systemic chemotherapy, prior to the use of local ophthalmic therapy. Response to subsequent courses will help define response to combined systemic chemotherapy and local ophthalmic therapy. Number eyes with Type I, II, III or IV response after first course of therapy |
| Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level | 2 years after enrollment | EFSR will be estimated for patients who respond to vincristine and carboplatin after an initial 1 cycle of chemoreduction |
| Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | 6 months after enrollment | Participants with Grade 3 and higher reported on protocol therapy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vincristine Sulfate and Carboplatin and Surgery Patients receive chemoreduction comprising carboplatin IV (Pts \< 36 months: 18.6 mg/kg Pts ≥ 36 months: 560 mg/m2) over 60 minutes followed by vincristine sulfate IV (Pts \< 36 months: 0.05 mg/kg Pts ≥36 months: 1.5 mg/m2) over 1-2 minutes on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the first course of chemoreduction, patients undergo standardized local ophthalmic therapy comprising local infrared laser therapy, cryosurgery, and/or radiation therapy (radioactive) plaque comprising iodine I 125 or ruthenium Ru 106. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 7 |
| Overall Study | Physician Decision | 2 |
Baseline characteristics
| Characteristic | Vincristine Sulfate and Carboplatin and Surgery |
|---|---|
| Age, Continuous | 0.3 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment Barbados | 1 participants |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 21 |
| serious Total, serious adverse events | 10 / 21 |
Outcome results
Primary
Event-free Survival
Proportion of patients with event free survival at 2 years. An event is defined as the need for non-protocol therapy, defined as additional on-protocol chemotherapy, enucleation or external beam radiation, among patients with Group B intraocular tumors with a schedule of neoadjuvant 2-agent (Vincristine/Carboplatin) chemotherapy (chemo-reduction) and standardized local ophthalmic therapy.
Time frame: At 2 years
Population: All eligible patients are reported. 7 patients were excluded due to ineligible status. Of the 7 patients, 1 was determined to have only a Group A involved eye and the other 6 had an intact eye that was Group C or D.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vincristine Sulfate and Carboplatin and Surgery | Event-free Survival | 0.65 Proportion of participants |
Secondary
Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level
EFSR will be estimated for patients who respond to vincristine and carboplatin after an initial 1 cycle of chemoreduction
Time frame: 2 years after enrollment
Population: There were 15 eligible patients who responded to vincristine and carboplatin after an initial 1 cycle of therapy. 7 patients were excluded due to ineligible status.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vincristine Sulfate and Carboplatin and Surgery | Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level | 0.60 Proportion of participants |
Secondary
Response Rate (RR) at Eye Levels After the First Course of Therapy
RR will be estimated. The response after 1 course of chemotherapy will be used to better define response to this neoadjuvant systemic chemotherapy, prior to the use of local ophthalmic therapy. Response to subsequent courses will help define response to combined systemic chemotherapy and local ophthalmic therapy. Number eyes with Type I, II, III or IV response after first course of therapy
Time frame: 1 month after enrollment
Population: Number of Group B eyes for the eligible patients. 4 patients were excluded due to ineligible status.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vincristine Sulfate and Carboplatin and Surgery | Response Rate (RR) at Eye Levels After the First Course of Therapy | 0.71 Proportion of eyes |
Secondary
Response Rate (RR) at Patient Level After the First Course of Therapy
RR will be estimated. The response after 1 course of chemotherapy will be used to better define response to this neoadjuvant systemic chemotherapy, prior to the use of local ophthalmic therapy. Response to subsequent courses will help define response to combined systemic chemotherapy and local ophthalmic therapy. Number of patients with Type I, II, III or IV response after first course of therapy
Time frame: 1 month after enrollment
Population: All eligible patients are reported. 7 patients were excluded due to ineligible status.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vincristine Sulfate and Carboplatin and Surgery | Response Rate (RR) at Patient Level After the First Course of Therapy | 0.71 Proportion of participants |
Secondary
Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
Participants with Grade 3 and higher reported on protocol therapy
Time frame: 6 months after enrollment
Population: All eligible patients are reported. 7 patients were excluded due to ineligible status.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vincristine Sulfate and Carboplatin and Surgery | Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Incidence of Catheter Related Infection | 1 Participants |
| Vincristine Sulfate and Carboplatin and Surgery | Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Incidence of Upper Respiratory Infection | 1 Participants |
| Vincristine Sulfate and Carboplatin and Surgery | Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Incidence of Dehydration | 1 Participants |
| Vincristine Sulfate and Carboplatin and Surgery | Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Incidence of Urticaria | 1 Participants |
| Vincristine Sulfate and Carboplatin and Surgery | Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 | Incidence of Neutrophils | 6 Participants |