Study of Treatment for Patients With Cancer of the Eye -Retinoblastoma

NCT00186888 | Completed Phase 3 Results DMC

• 3 other identifiers: RET5P01CA023099NCI-2011-01186
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

Brief Summary

Retinoblastoma is a childhood cancer which affects the retina of the eye. The retina is the light sensitive layer of tissue that lines the back of the eyeball; sends visual messages through the optic nerve to the brain. When only one eye is affected, this is known as unilateral retinoblastoma and when both eyes are affected, it is called bilateral retinoblastoma. Treatment for retinoblastoma is individualized for each patient and is based on the form and the stage of the disease (inside the eye or has moved outside). The main goal is always to cure the cancer, and save the life of the child. Treatments are also designed with the hope of saving the vision, while completely destroying the tumor. Therapies may involve surgery, chemotherapy, radiation, and other treatments called focal treatments. Focal treatments may be laser therapy, freezing, or heat treatments meant to shrink and kill the tumor. In this study, researchers want to investigate how different participants respond to different therapies that are individualized specifically for them. Participants will be divided into three main groups, depending on whether the disease is unilateral or bilateral, and the stage of the disease. One of the main objectives of the study is to investigate how advanced tumors in children with bilateral disease respond to a new combination of chemotherapy with topotecan and vincristine, with G-CSF support. In order to improve results, some children with very advanced disease may receive carboplatin chemotherapy given around the eye at the same time that they receive topotecan by vein. Also, because children with retinoblastoma are diagnosed so early in life and the vision may be significantly impaired, this study will investigate how children develop and how the brain adjusts and compensates for the visual deficits. Finally, this study also investigates the biology of retinoblastoma, in order to understand better how this cancer develops.

Conditions

Retinoblastoma; Retinal Neoplasm

Keywords

Cancer of the Eye; Eye Enucleation

Outcome Measures

Primary Outcomes (1)

• Stratum B Response to Window Therapy

  The primary outcome is to estimate the proportion of stratum B patients responding to 2 courses of window therapy consisting of vincristine and topotecan. Complete Response is the complete regression of all apparent tumor masses in the funduscopic examination and by MRI and ultrasound (US). Partial Response is defined as greater than 50% (but less than 100%) reduction of the tumor masses in the funduscopic examination and by US and MRI, without the appearance of any new lesions. The response must persist for at least 4 weeks. Stratum A and C did not receive window therapy.

  Six weeks post window therapy

Secondary Outcomes (29)

• Stratum B Response Rate of Early Stage Eyes to Window Therapy

  Six weeks post window therapy.

• Relationship Between Topotecan Clearance (CL) and CYP3A4/5 Genotype in Stratum B Participants.

  Courses 1, 2, 5, and 8

• Relationship Between Topotecan Clearance (CL) and ABCG2/B1 Genotype in Stratum B Participants.

  Courses 1, 2, 5, and 8

• Event-free Survival of Stratum B Patients Responding to Window Treatment

  From date on-study to an event or last follow-up

• Ocular Survival of Stratum B Patients Responding to Window Treatment

  From date on-study to an event or last follow-up

Study Arms (3)

Stratum A

OTHER

Patients with early bilateral or unilateral, or patients with bilateral that have already had the advanced eye enucleated. Treatment included vincristine and carboplatin for 8 courses, given at 3-4 week intervals. Focal therapies any time after second course can include cryotherapy, laser photocoagulation, thermotherapy, and plaque radiotherapy

Procedure: Enucleation; Drug: Vincristine, Carboplatin; Procedure: Focal Therapies; Radiation: External Beam Radiation; Other: G-CSF

Stratum B

OTHER

Patients with bilateral disease (at least one advanced stage eye), candidate for conservative management. Treatment included window treatment with vincristine and topotecan, Followed by 3 more courses of vincristine-topotecan if they had a response to the window+ 6 courses of vincristine and carboplatin. If they do not respond to the window, they receive 6 courses of vincristine, carboplatin, and etoposide. Periocular carboplatin is also given three times, depending on whether they respond to window. External Beam Radiation 44-46 Gy administered using standard practices.

Procedure: Enucleation; Drug: Vincristine, Carboplatin; Procedure: Focal Therapies; Radiation: External Beam Radiation; Drug: Vincristine and Topotecan; Drug: Vincristine + Carboplatin + Etoposide; Procedure: Periocular carboplatin; Other: G-CSF

Stratum C

OTHER

Patients with advanced unilateral advanced intraocular disease. First intervention is enucleation. If enucleated eye does not have disease outside the retina (low risk), no additional treatment is given. For patients whose enucleated eye shows tumor outside the retina (intermediate risk), they will receive 4 courses of vincristine, cyclophosphamide, and doxorubicin followed by G-CSF. For patients with high risk disease (involvement of the sclera, optic nerve at the level of the cut-end), treatment after enucleation is 6 courses of alternating chemotherapy with vincristine, carboplatin, etoposide (VCE) to alternate with vincristine, cyclophosphamide, and doxorubicin (VCD). High risk patients also receive external-beam radiation therapy.

Procedure: Enucleation; Radiation: External Beam Radiation; Drug: vincristine, cyclophosphamide, and doxorubicin; Drug: Vincristine, Carboplatin and Etoposide; Other: G-CSF

Interventions

Enucleation PROCEDURE

Enucleation (possibly associated with all treatment strata/arms. For Stratum A, patients with bilateral disease will have surgery to remove the advanced eye before chemotherapy, or patients that have disease progression after chemotherapy may have surgery to remove the affected eye. For Stratum B, Surgical removal of the affected eye may be required in cases of disease progression For Stratum C, first intervention is removal of the affected eye.

Stratum A; Stratum B; Stratum C

Vincristine, Carboplatin DRUG

(Stratum A subjects receive 8 courses every 3-4 weeks, Stratum B subjects receive this combination for Courses 3, 4, 6, 7, 9, and 10 after the window, if they respond to window therapy) Vincristine dosage\< 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1.

Also known as: Oncovin + Paraplatin

Stratum A; Stratum B

Focal Therapies PROCEDURE

Method will be at the discretion of the treating team, used after second course of chemotherapy. Cryotherapy- freezing of affected tissue, Laser photocoagulation- using lasers to destroy affected tissue, Thermotherapy and thermochemotherapy- using heat or heat/chemotherapy combination to destroy diseased tissue, and Episcleral plaque brachytherapy- radiation insertions in the diseased area to destroy affected tissue.

Stratum A; Stratum B

External Beam Radiation RADIATION

44-46 Gy administered using standard practices , limiting dose to normal tissues to subjects with recurrent or progressive disease not considered controllable with focal treatments, Stratum B subjects with suspected active disease after completing therapy, or patients considered to have high-risk disease.

Stratum A; Stratum B; Stratum C

Vincristine and Topotecan DRUG

(Stratum B subjects receive two up-front courses of vincristine and topotecan, given in 21-day intervals, then those who respond receive 3 additional courses (courses 5, 8, and 11) after the window. Dosages are the same for both window and subsequent courses: Vincristine: \< 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Topotecan: TSE of 140 ± 20 ng/ml\*hr, daily for 5 consecutive days, infused over 30 minutes.

Also known as: Oncovin + Hycamtin

Stratum B

Vincristine + Carboplatin + Etoposide DRUG

Stratum B patients that do not respond to window receive 6 courses of this combination. Vincristine: \< 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1 Etoposide, \< 12 months of age: 3.3 mg/kg/d i.v. days 1 - 3, ≥ 12 months of age: 100 mg/m2/d i.v. days 1 - 3

Also known as: Oncovin + Paraplatin + VP-16

Stratum B

vincristine, cyclophosphamide, and doxorubicin DRUG

(High risk Stratum C patients in courses 2, 4, and 6 after enucleation, intermediate risk stratum C patients for four consecutive courses after enucleation) Vincristine: \< 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Cyclophosphamide: \< 12 months of age: 40 mg/kg i.v. day 1, ≥ 12 months of age: 1,200 mg/m2 i.v. day 1, MESNA 200 mg/m2 at 0, 3, 6, and 9 hours Doxorubicin \< 12 months of age: 1.5 mg/kg i.v. day 1, ≥ 12 months of age: 45 mg/m2 i.v. day 1

Also known as: Onconvin and Cytoxan and Adriamycin

Stratum C

Vincristine, Carboplatin and Etoposide DRUG

High risk Stratum C patients in courses 1, 3, and 5 after enucleation: Vincristine: \< 12 months of age: 0.05 mg/kg i.v. day 1, ≥ 12 months of age: 1.5 mg/m2 i.v. day 1 (max. dose 2 mg) Carboplatin will be administered i.v. to achieve an AUC of 6.5 mg/ml/min, day 1 Etoposide, \< 12 months of age: 3.3 mg/kg/d i.v. days 1 - 3, ≥ 12 months of age: 100 mg/m2/d i.v. days 1 - 3

Also known as: Onconvin and Paraplatin and Vepesid

Stratum C

Periocular carboplatin PROCEDURE

Periocular (subtenon) carboplatin 20 mg, one injection, in courses 5, 8, and 11 in patients responding to the VT window, and in courses 1, 3, and 6 of VCE in patients not responding to the VT window, when active vitreous disease is present. Carboplatin 20 mg will be diluted in 2 mL of NS or D5W and given by subtenon administration while the patient is under general anesthesia.

Also known as: Paraplatin

Stratum B

G-CSF OTHER

G-CSF (5 mcg/kg/day), will be administered starting 24-36 hours after the completion of each course of chemotherapy, for 7 to 10 days, until ANC is \> 2,000/mL in one occasion after the expected nadir.

Also known as: Filgrastim, Neupogen

Stratum A; Stratum B; Stratum C

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have newly diagnosed intraocular retinoblastoma, previously untreated. Patients previously diagnosed with unilateral retinoblastoma treated surgically (or with focal therapies), who develop asynchronous involvement of the contralateral eye, will be eligible for study.
• Must have a life expectancy of at least 8 weeks.
• Must have Performance Status (ECOG) of 0-2.
• Patients must have an adequate liver function, as defined by bilirubin less than or equal to 3 x normal, and SGOT and SGPT less than or equal to 3x normal.
• Patients must have adequate renal function as defined by serum creatinine less than or equal to 3x normal for age.
• Legal guardians must sign an informed consent indicating that they are aware of this study, its possible benefits, and toxic side effects. Legal guardians will be given a copy of the consent form.

You may not qualify if:

• Previously treated patients
• Presence of metastatic disease or orbital involvement
• Patients must not have an invasive infection at time of protocol entry.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (1)

• King BA, Sahr N, Sykes A, Wilson MW, Brennan RC. Chemoreduction with topotecan and vincristine: Quantifying tumor response in bilateral retinoblastoma patients. Pediatr Blood Cancer. 2021 Apr;68(4):e28882. doi: 10.1002/pbc.28882. Epub 2021 Jan 28.

  PMID: 33507604 DERIVED

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Retinoblastoma; Retinal Neoplasms; Eye Neoplasms

Interventions

Eye Enucleation; Vincristine; Carboplatin; Topotecan; Etoposide; Cyclophosphamide; Doxorubicin; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Intervention Hierarchy (Ancestors)

Ophthalmologic Surgical Procedures; Surgical Procedures, Operative; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Coordination Complexes; Organic Chemicals; Camptothecin; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Ibrahim Qaddoumi MD
• Organization: St. Jude Children's Research Hospital

info@stjude.org

1-866-278-5833

Study Officials

• Ibrahim Qaddoumi, M.D.

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 16, 2005
• Study Start: April 7, 2005
• Primary Completion: November 1, 2013
• Study Completion: November 12, 2024
• Last Updated: September 4, 2025
• Results First Posted: August 30, 2011

Record last verified: 2025-09

Locations

US (1)