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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-00422 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| ARET0331 | |||
| CDR0000355721 | |||
| COG-ARET0331 | |||
| ARET0331 | Other Identifier | Children's Oncology Group | |
| ARET0331 | Other Identifier | CTEP | |
| U10CA098543 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (chemotherapy, surgery) | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carboplatin | Drug | Given IV |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | At 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Newly diagnosed Group B intraocular retinoblastoma meeting 1 of the following criteria:
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:
Group B: Tumors more than 3 mm meeting the following criteria:
Group E: Must have ≥ 1 of the following present:
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
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| Name | Affiliation | Role |
|---|---|---|
| Debra L Friedman | Children's Oncology Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States | ||
| Lurie Children's Hospital-Chicago |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. cryosurgery: Application of extreme cold to destroy abnormal or diseased tissue. infrared laser therapy: Laser therapy or "photobiomodulation" is the use of specific wavelength of light (red and near-infrared) to create therapeutic effects iodine I 125: Undergo radioactive therapy ruthenium Ru 106: Undergo radioactive therapy carboplatin: Given IV vincristine sulfate: Given IV |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Cryosurgery | Procedure |
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| Infrared Laser Therapy | Procedure |
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| Iodine I-125 | Radiation | Undergo radioactive therapy |
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| Radiation Therapy | Radiation | Undergo radioactive therapy |
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| Ruthenium Ru-106 | Radiation | Undergo radioactive therapy |
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| Vincristine Sulfate | Drug | Given IV |
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| 1 month after enrollment |
| 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 | 1 month after enrollment |
| 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 | 2 years after enrollment |
| 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 | 6 months after enrollment |
| Chicago |
| Illinois |
| 60611 |
| United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Children's Oncology Group | Philadelphia | Pennsylvania | 19104 | United States |
| Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | 77030 | United States |
| Fred Hutchinson Cancer Research Center | Seattle | Washington | 98109 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Number | 95% Confidence Interval | Proportion of participants | At 2 years |
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| 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 | All eligible patients are reported. 7 patients were excluded due to ineligible status. | Posted | Number | 95% Confidence Interval | Proportion of participants | 1 month after enrollment |
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| 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 | Number of Group B eyes for the eligible patients. 4 patients were excluded due to ineligible status. | Posted | Number | 95% Confidence Interval | Proportion of eyes | 1 month after enrollment |
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| 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 | 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. | Posted | Number | 95% Confidence Interval | Proportion of participants | 2 years after enrollment |
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| 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 | All eligible patients are reported. 7 patients were excluded due to ineligible status. | Posted | Number | Participants | 6 months after enrollment |
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Adverse events grade 3 and above were considered as Serious Adverse Events in this study. All eligible patients are reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 10 | 21 | 3 | 21 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Catheter related infection | Infections and infestations | Grades 3-5 |
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| Dehydration | Metabolism and nutrition disorders | Grades 3-5 |
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| Neutrophil count decreased | Investigations | Grades 3-5 |
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| Upper respiratory infection | Infections and infestations | Grades 3-5 |
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| Urticaria | Skin and subcutaneous tissue disorders | Grades 3-5 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count decreased | Investigations | Grades 1-2 |
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| Platelet count decreased | Investigations | Grades 1-2 |
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Must obtain prior Sponsor approval.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Results Reporting Coordinator | Children's Oncology Group | 352-273-0567 | resultsreportingcoordinator@childrensoncologygroup.org |
| ID | Term |
|---|---|
| D016190 | Carboplatin |
| D003452 | Cryosurgery |
| C000614960 | Iodine-125 |
| D011878 | Radiotherapy |
| D011827 | Radiation |
| C000615522 | Ruthenium-106 |
| D014750 | Vincristine |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D055011 | Ablation Techniques |
| D013514 | Surgical Procedures, Operative |
| D013812 | Therapeutics |
| D055585 | Physical Phenomena |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Units | Counts |
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| Participants |
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| Participants |
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