Individualized Therapy for Retinoblastoma

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Metastatic disease, Orbital involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 months

107 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Ibrahim Qaddoumi, M.D.

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for children with newly diagnosed retinoblastoma, a type of eye cancer. They must have good liver and kidney function, be expected to live at least 8 weeks, and have a performance status showing they can do some daily activities. Kids who've had surgery or focal treatments on one eye but then get cancer in the other are also eligible. Children with spread of cancer outside the eye or an active infection cannot join.

Inclusion Criteria

I have a new diagnosis of eye cancer and haven't been treated, or I had treatment for cancer in one eye and now the other is affected.

Must have a life expectancy of at least 8 weeks.

I am able to get out of my bed or chair and move around.

Exclusion Criteria

I do not have a serious infection right now.

Patients who have received treatment for this condition before.

My cancer has spread to other parts of my body or affects my eye socket.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive individualized treatment based on the form and stage of retinoblastoma, including chemotherapy, surgery, and focal treatments.

6-12 months

Regular visits for chemotherapy cycles and focal treatments

Follow-up

Participants are monitored for ocular survival and event-free survival, as well as cognitive and developmental assessments.

5 years

Annual visits for assessments and monitoring

Long-term Follow-up

Participants are monitored for changes in visual cortex function and development of pineal cysts.

6 years after last patient enrollment

Treatment Details

Interventions

• Carboplatin
• Doxorubicin
• Enucleation
• Etoposide
• External Beam Radiation
• Focal Therapies
• G-CSF
• Periocular carboplatin
• Vincristine
• Vincristine and Carboplatin
• Vincristine and Topotecan
• Vincristine, Carboplatin and Etoposide

Trial Overview The study tests various treatments based on whether one or both eyes are affected and how advanced the disease is. It includes chemotherapy combinations like topotecan and vincristine (with G-CSF support), carboplatin around the eye, plus potential surgeries and focal therapies like laser treatment. The aim is to cure cancer, save vision, understand how kids adapt visually post-treatment, and learn more about retinoblastoma biology.

Participant Groups

Group I: Stratum C Experimental Treatment 5 Interventions

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.

Group II: Stratum B Experimental Treatment 8 Interventions

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.

Group III: Stratum A Experimental Treatment 5 Interventions

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

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+