RetinoblastomaPhase 2NCT00110110
Combination Chemotherapy and Cyclosporine Followed by Focal Therapy for Bilateral Retinoblastoma
A Phase 2 study testing filgrastim, Carboplatin and Cyclosporine in people with Retinoblastoma, run by The Hospital for Sick Children at 6 sites in 4 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin, etoposide, and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. Read more about this study
- Who is it for?
- Ages 30 days and older
- Conditions the study is for
- Retinoblastoma
- What is being tested?
- filgrastim, Carboplatin and Cyclosporine
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 6 sitesin 4 countries
- Study dates
- Jun 2004to 31 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 days and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
>>INCLUSION CRITERIA<<
DISEASE CHARACTERISTICS:
- Clinical diagnosis of bilateral intraocular retinoblastoma (RB)
- International Intraocular Retinoblastoma Classification (IIRC) Group B, C, or D disease in 1 or both eyes
- IIRC Group E disease in 1 eye allowed provided the eye was enucleated at diagnosis AND there is no extraocular RB in the enucleated eye by histologic confirmation AND there is IIRC Group B, C, or D disease in the remaining eye
PATIENT CHARACTERISTICS:
Age
- Over 30 days
Performance status
- Not specified
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- AST and ALT < 2 times upper limit of normal (ULN)
- Conjugated and unconjugated bilirubin < 2 times ULN
Renal
- Creatinine < 1.5 times ULN
- Glomerular filtration rate (GFR) ≥ 100 mL/min* NOTE: *A 4-hour IV hydration is allowed if GFR is low due to poor hydration or transient dehydration
Other
- Meets 1 of the following auditory criteria:
- Normal audiogram
- At least normal responses to speech by audiogram
- Documentation of hearing by acoustic emission test
- Recording of evoked potentials by auditory brain stem response
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- See Disease Characteristics >>EXCLUSION CRITERIA<<
- IIRC Group A disease in 1 or both eyes
- unilateral RB
- extraocular or metastatic RB
- younger than 30 days
- Glomerular filtration rate (GFR) < 100 mL/min
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
Canada3 sites
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, H3H 1P3
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Children's and Women's Hospital of British Columbia
Vancouver, British Columbia, V6H 3V4
Singapore1 site
Kandang Kerbau Women's and Children's Hospital
Singapore, 229899
About this study
Official title: Multicenter Phase II Study for International Intraocular Retinoblastoma Classification Groups B, C & D Tumors Treated With Carboplatin-Etoposide-Vincristine-Cyclosporine-Focal Therapy Multimodality Protocol (OCRN Multicenter RB 2003)
RATIONALE: Drugs used in chemotherapy, such as carboplatin, etoposide, and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving cyclosporine together with chemotherapy may reduce drug resistance and allow the tumor cells to be killed. Cryotherapy kills tumor cells by freezing them. Laser therapy uses light to kill tumor cells. Giving combination chemotherapy together with cyclosporine followed by cryotherapy and/or laser therapy may be an effective treatment for retinoblastoma.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with cyclosporine followed by cryotherapy and/or laser therapy works in treating patients with newly diagnosed retinoblastoma in both eyes.
Read the detailed description
OBJECTIVES:
Primary
- Compare the efficacy of neoadjuvant high-dose carboplatin and etoposide, vincristine, and cyclosporine (CSA) followed by ophthalmic focal therapy comprising cryotherapy and/or laser therapy to historical world data of chemotherapy treatment without CSA, in terms of increasing the proportion of eyes that remain relapse free and do not require external beam radiotherapy and/or enucleation, in patients with newly diagnosed Group B, C, or D bilateral intraocular retinoblastoma.
Secondary
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study.
Patients receive high-dose carboplatin IV over 30 minutes on day 1; vincristine IV over 5 minutes and high-dose etoposide IV over 25 minutes on day 2; cyclosporine IV over 1 hour before chemotherapy and then over 2 hours after chemotherapy on days 1 and 2, and filgrastim (G-CSF) subcutaneously once daily beginning on day 3 and continuing until day 16 or until blood counts recover. Treatment repeats every 21 days for a total of 3 courses for patients with Group B disease and a total of 6 courses for patients with Group C or D disease.
Patients undergo eye examination under anesthesia (EUA) at initial staging and then before each course of chemotherapy. Patients with small peripheral tumors in eyes without retinal detachment undergo minimal focal therapy (mainly cryotherapy) during EUA at initial staging and then after chemotherapy courses 1 and 2. At EUA after the third and subsequent courses of chemotherapy, patients with tumors that have sufficiently reduced in size undergo additional cryotherapy or laser therapy. After completion of chemotherapy, patients with any suspicious, active, or reactivated tumor undergo additional cryotherapy and/or laser therapy during EUA approximately every 4-8 weeks (or at longer intervals) for up to 5 years (as needed).
After completion of study chemotherapy, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually for 1 year.
PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 2.4 years.
- Conditions
- Retinoblastoma
- Being tested
- filgrastim, Carboplatin, Cyclosporine, Etoposide, vincristine sulfate
- Keywords
- intraocular retinoblastoma
- Medical subject headings
- Retinoblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
Also called granulocyte colony-stimulating factor (G-CSF)
Given after chemo cycle for 7 days or until neutrophil counts return to normal.
CarboplatinDrug
Given at 28 mg/kg/dose.
CyclosporineDrug
Given at 33 mg/kg/dose
EtoposideDrug
Given at 12 mg/kg/dose
Also called vincristine
Given at 0.025 mg/kg/dose for the first cycle and 0.05 mg/kg/dose for subsequent cycles if first cycle well-tolerated
cryosurgeryProcedure or surgery
Also called cryotherapy
Local application of extreme cold to destroy residual tumor.
laser therapyProcedure or surgery
Local and precise application of laser beams to destroy residual tumor.
| Study group | Role | What they receive |
|---|---|---|
| CEV Chemo + Cyclosporine & Focal Therapy | Experimental | Systemic carboplatin (28 mg/kg/dose), etoposide (12 mg/kg/dose) and vincristine sulfate (0.025 mg/kg/dose for the first cycle and 0.05 mg/kg/dose for subsequent cycles if first cycle well-tolerated) chemotherapy given with cyclosporin A (33 mg/kg/dose). Following 4-6 cycles CEV chemotherapy (depending on tumor stage) given every 3 weeks, focal laser therapy and/or cryosurgery are applied for tumor consolidation. Filgrastim is given after each chemotherapy cycle to prevent severe neutropenia. Receives: Biological: filgrastim; Drug: Carboplatin; Drug: Cyclosporine; Drug: Etoposide; Drug: vincristine sulfate; Procedure: cryosurgery; Procedure: laser therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparing efficacy of study treatment with historic world data, in terms of increasing the proportion of eyes that remains relapse-free while avoiding external beam radiation and/or enucleation
Efficacy
Measured: 5 year follow-up per patient
Secondary outcomes (1)
Toxicity during treatment
Toxicity
Measured: 5 year follow-up per patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2005 (estimated)
- Study startJun 2004
- Primary completion20 Apr 2016
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RetinoblastomaStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 71 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Terry Fox Foundation
- Responsible party
- Principal investigator, Helen Chan, The Hospital for Sick Children
- Investigators
- Brenda L Gallie, MD, Principal investigator, The Hospital for Sick ChildrenElise Heon, MD, Principal investigator, The Hospital for Sick ChildrenHelen SL Chan, MD, BS, Study chair, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00110110
- Sponsor's protocol ID
- 1000005587
- Other IDs
- HFSC-OCRN-RB-2003, CDR0000422340
- Status last verified
- Apr 2024
- First submitted
- 3 May 2005
- Last updated
- 17 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Phase II Study for International Intraocular Retinoblastoma Classification Groups B, C & D Tumors Treated With Carboplatin-Etoposide-Vincristine-Cyclosporine-Focal Therapy Multimodality Protocol (OCRN Multicenter RB 2003)
- ClinicalTrials.gov ID
- NCT00110110
- Acronym / sponsor ID
- 1000005587
- Conditions
- Retinoblastoma
- Keywords
- intraocular retinoblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 71 participants (estimated)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Terry Fox Foundation
- Study start
- Jun 2004 (actual)
- Primary completion
- 20 Apr 2016 (actual)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 4 May 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as carboplatin, etoposide, and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving cyclosporine together with chemotherapy may reduce drug resistance and allow the tumor cells to be killed. Cryotherapy kills tumor cells by freezing them. Laser therapy uses light to kill tumor cells. Giving combination chemotherapy together with cyclosporine followed by cryotherapy and/or laser therapy may be an effective treatment for retinoblastoma.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with cyclosporine followed by cryotherapy and/or laser therapy works in treating patients with newly diagnosed retinoblastoma in both eyes.
Detailed description
OBJECTIVES:
Primary
- Compare the efficacy of neoadjuvant high-dose carboplatin and etoposide, vincristine, and cyclosporine (CSA) followed by ophthalmic focal therapy comprising cryotherapy and/or laser therapy to historical world data of chemotherapy treatment without CSA, in terms of increasing the proportion of eyes that remain relapse free and do not require external beam radiotherapy and/or enucleation, in patients with newly diagnosed Group B, C, or D bilateral intraocular retinoblastoma.
Secondary
- Determine the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study.
Patients receive high-dose carboplatin IV over 30 minutes on day 1; vincristine IV over 5 minutes and high-dose etoposide IV over 25 minutes on day 2; cyclosporine IV over 1 hour before chemotherapy and then over 2 hours after chemotherapy on days 1 and 2, and filgrastim (G-CSF) subcutaneously once daily beginning on day 3 and continuing until day 16 or until blood counts recover. Treatment repeats every 21 days for a total of 3 courses for patients with Group B disease and a total of 6 courses for patients with Group C or D disease.
Patients undergo eye examination under anesthesia (EUA) at initial staging and then before each course of chemotherapy. Patients with small peripheral tumors in eyes without retinal detachment undergo minimal focal therapy (mainly cryotherapy) during EUA at initial staging and then after chemotherapy courses 1 and 2. At EUA after the third and subsequent courses of chemotherapy, patients with tumors that have sufficiently reduced in size undergo additional cryotherapy or laser therapy. After completion of chemotherapy, patients with any suspicious, active, or reactivated tumor undergo additional cryotherapy and/or laser therapy during EUA approximately every 4-8 weeks (or at longer intervals) for up to 5 years (as needed).
After completion of study chemotherapy, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually for 1 year.
PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 2.4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CEV Chemo + Cyclosporine & Focal Therapy | Experimental | Biological: filgrastim, Drug: Carboplatin, Drug: Cyclosporine, Drug: Etoposide, Drug: vincristine sulfate, Procedure: cryosurgery, Procedure: laser therapySystemic carboplatin (28 mg/kg/dose), etoposide (12 mg/kg/dose) and vincristine sulfate (0.025 mg/kg/dose for the first cycle and 0.05 mg/kg/dose for subsequent cycles if first cycle well-tolerated) chemotherapy given with cyclosporin A (33 mg/kg/dose). Following 4-6 cycles CEV chemotherapy (depending on tumor stage) given every 3 weeks, focal laser therapy and/or cryosurgery are applied for tumor consolidation. Filgrastim is given after each chemotherapy cycle to prevent severe neutropenia. |
Who may qualify
- Ages
- 30 days and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| filgrastimAlso: granulocyte colony-stimulating factor (G-CSF)Given after chemo cycle for 7 days or until neutrophil counts return to normal. | Biological | CEV Chemo + Cyclosporine & Focal Therapy |
| CarboplatinGiven at 28 mg/kg/dose. | Drug | CEV Chemo + Cyclosporine & Focal Therapy |
| CyclosporineGiven at 33 mg/kg/dose | Drug | CEV Chemo + Cyclosporine & Focal Therapy |
| EtoposideGiven at 12 mg/kg/dose | Drug | CEV Chemo + Cyclosporine & Focal Therapy |
| vincristine sulfateAlso: vincristineGiven at 0.025 mg/kg/dose for the first cycle and 0.05 mg/kg/dose for subsequent cycles if first cycle well-tolerated | Drug | CEV Chemo + Cyclosporine & Focal Therapy |
| cryosurgeryAlso: cryotherapyLocal application of extreme cold to destroy residual tumor. | Procedure or surgery | CEV Chemo + Cyclosporine & Focal Therapy |
| laser therapyLocal and precise application of laser beams to destroy residual tumor. | Procedure or surgery | CEV Chemo + Cyclosporine & Focal Therapy |
Primary outcome
Comparing efficacy of study treatment with historic world data, in terms of increasing the proportion of eyes that remains relapse-free while avoiding external beam radiation and/or enucleation
Time frame: 5 year follow-up per patient
Efficacy
1 secondary outcome
Toxicity during treatment
Time frame: 5 year follow-up per patient
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brenda L Gallie, MD principal investigator
The Hospital for Sick Children
Elise Heon, MD principal investigator
The Hospital for Sick Children
Helen SL Chan, MD, BS study chair
The Hospital for Sick Children
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing filgrastim, Carboplatin and Cyclosporine in people with Retinoblastoma, run by The Hospital for Sick Children at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada, Chile, India, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparing efficacy of study treatment with historic world data, in terms of increasing the proportion of eyes that remains relapse-free while avoiding external beam radiation and/or enucleation (time frame: 5 year follow-up per patient). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.