Trial Outcomes & Findings for Neoadjuvant Carboplatin and Vincristine and Standard Local Ophthalmic Therapy in Treating Patients With Intraocular Retinoblastoma (NCT NCT00079417)

Last Updated: 2023-03-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

28 participants

Primary outcome timeframe

At 2 years

Results posted on

2023-03-13

Participant Flow

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	28
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Overall Study Physician Decision	2
Overall Study Ineligible	7

Baseline Characteristics

Neoadjuvant Carboplatin and Vincristine and Standard Local Ophthalmic Therapy in Treating Patients With Intraocular Retinoblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vincristine Sulfate and Carboplatin and Surgery n=28 Participants 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.
Age, Continuous	0.3 Years n=99 Participants
Sex: Female, Male Female	13 Participants n=99 Participants
Sex: Female, Male Male	15 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=99 Participants
Race (NIH/OMB) Black or African American	4 Participants n=99 Participants
Race (NIH/OMB) White	19 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=99 Participants
Region of Enrollment United States	27 participants n=99 Participants
Region of Enrollment Barbados	1 participants n=99 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Vincristine Sulfate and Carboplatin and Surgery n=21 Participants 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
Event-free Survival	0.65 Proportion of participants Interval 0.4 to 0.82

SECONDARY outcome

Timeframe: 1 month after enrollment

Population: All eligible patients are reported. 7 patients were excluded due to ineligible status.

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

Outcome measures

Outcome measures
Measure	Vincristine Sulfate and Carboplatin and Surgery n=21 Participants 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
Response Rate (RR) at Patient Level After the First Course of Therapy	0.71 Proportion of participants Interval 0.48 to 0.89

SECONDARY outcome

Timeframe: 1 month after enrollment

Population: Number of Group B eyes for the eligible patients. 4 patients were excluded due to ineligible status.

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

Outcome measures

Outcome measures
Measure	Vincristine Sulfate and Carboplatin and Surgery n=24 Participants 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
Response Rate (RR) at Eye Levels After the First Course of Therapy	0.71 Proportion of eyes Interval 0.49 to 0.87

SECONDARY outcome

Timeframe: 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.

EFSR will be estimated for patients who respond to vincristine and carboplatin after an initial 1 cycle of chemoreduction

Outcome measures

Outcome measures
Measure	Vincristine Sulfate and Carboplatin and Surgery n=15 Participants 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
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 Interval 0.4 to 0.91

SECONDARY outcome

Timeframe: 6 months after enrollment

Population: All eligible patients are reported. 7 patients were excluded due to ineligible status.

Participants with Grade 3 and higher reported on protocol therapy

Outcome measures

Outcome measures
Measure	Vincristine Sulfate and Carboplatin and Surgery n=21 Participants 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
Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 Incidence of Dehydration	1 Participants
Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 Incidence of Urticaria	1 Participants
Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 Incidence of Neutrophils	6 Participants
Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 Incidence of Catheter Related Infection	1 Participants
Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 Incidence of Upper Respiratory Infection	1 Participants

Adverse Events

Vincristine Sulfate and Carboplatin and Surgery

Serious events: 10 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vincristine Sulfate and Carboplatin and Surgery n=21 participants at risk 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.
Infections and infestations Catheter related infection	4.8% 1/21 Adverse events grade 3 and above were considered as Serious Adverse Events in this study. All eligible patients are reported.
Metabolism and nutrition disorders Dehydration	4.8% 1/21 Adverse events grade 3 and above were considered as Serious Adverse Events in this study. All eligible patients are reported.
Investigations Neutrophil count decreased	28.6% 6/21 Adverse events grade 3 and above were considered as Serious Adverse Events in this study. All eligible patients are reported.
Infections and infestations Upper respiratory infection	4.8% 1/21 Adverse events grade 3 and above were considered as Serious Adverse Events in this study. All eligible patients are reported.
Skin and subcutaneous tissue disorders Urticaria	4.8% 1/21 Adverse events grade 3 and above were considered as Serious Adverse Events in this study. All eligible patients are reported.

Other adverse events

Other adverse events
Measure	Vincristine Sulfate and Carboplatin and Surgery n=21 participants at risk 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.
Investigations Neutrophil count decreased	4.8% 1/21 Adverse events grade 3 and above were considered as Serious Adverse Events in this study. All eligible patients are reported.
Investigations Platelet count decreased	9.5% 2/21 Adverse events grade 3 and above were considered as Serious Adverse Events in this study. All eligible patients are reported.

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 352-273-0567

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Must obtain prior Sponsor approval.
Publication restrictions are in place

Restriction type: OTHER