Combination Chemotherapy + Cyclosporine and Focal Therapy for Retinoblastoma

Not currently recruiting at 5 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: The Hospital for Sick Children

Must be taking: Cyclosporine

Disqualifiers: Unilateral RB, Metastatic RB, others

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

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

Compensation: Varies

Number of Visits: 10

Duration: 9-18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for retinoblastoma, a type of eye cancer affecting both eyes. The goal is to evaluate the effectiveness of a combination of chemotherapy drugs (Carboplatin, Etoposide, and Vincristine sulfate) and cyclosporine (an immunosuppressant), followed by cryotherapy (freezing) and laser therapy. Researchers aim to determine if adding cyclosporine enhances chemotherapy's effectiveness against resistant tumors. Suitable participants have a clinical diagnosis of retinoblastoma in both eyes, excluding the least severe form (Group A) and any signs of the disease outside the eye. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to advance treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of carboplatin, etoposide, and vincristine with cyclosporine is generally well-tolerated by patients with retinoblastoma. Studies have found that when children receive the correct dose of carboplatin, hearing problems are rare. This drug combination does not appear to increase the risk of more serious conditions like leukemia.

For treatments that focus directly on the eye, such as freezing (cryotherapy) and laser therapy, evidence indicates they are safe and effective for retinoblastoma. Laser therapy, in particular, has been safely used on its own for small tumors.

Overall, the treatments in this trial have a strong safety record based on past use. Existing data reassures participants about the safety of these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment because it combines chemotherapy with cyclosporine to potentially enhance effectiveness against retinoblastoma. Unlike standard treatments that rely solely on chemotherapy or focal therapies like laser therapy, this approach uses cyclosporine to inhibit a specific drug-resistant protein, possibly making the chemotherapy more effective. Additionally, the treatment includes focal therapies like laser therapy and cryosurgery after chemotherapy, which could help ensure thorough tumor reduction. Overall, this combination could offer a more comprehensive strategy to combat retinoblastoma than current options.

What evidence suggests that this trial's treatments could be effective for retinoblastoma?

In this trial, participants will receive a combination of the drugs carboplatin, etoposide, and vincristine with cyclosporine. Research has shown this combination to be promising for treating retinoblastoma, a type of eye cancer. One study found that this combination was very successful in saving eyes from removal. Cyclosporine may enhance chemotherapy effectiveness by reducing tumor cell resistance to the drugs. Additionally, focal therapies such as cryotherapy, which involves freezing tumor cells, and laser therapy will be used for tumor consolidation. Cryotherapy proved effective in about 70% of cases when used alone, and laser therapy also showed good results in saving eyes when combined with chemotherapy. Together, these treatments offer strong potential to improve outcomes for retinoblastoma patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Helen SL Chan, MD, BS

Principal Investigator

The Hospital for Sick Children

Elise Heon, MD

Principal Investigator

The Hospital for Sick Children

Brenda L Gallie, MD

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

This trial is for patients with bilateral retinoblastoma, a type of eye cancer, specifically those with IIRC Group B, C, or D disease in at least one eye. Suitable participants are over 30 days old and have normal liver and kidney function tests. Those with unilateral retinoblastoma, metastatic disease, or very young infants under 30 days old cannot join.

Inclusion Criteria

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

Age over 30 days

AST and ALT < 2 times upper limit of normal (ULN)

Exclusion Criteria

You have a type of eye cancer called retinoblastoma that has spread outside of the eye.

IIRC Group A disease in 1 or both eyes

Unilateral RB

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high-dose carboplatin, etoposide, vincristine, and cyclosporine chemotherapy followed by focal therapy with cryotherapy and/or laser therapy

9-18 weeks

Every 3 weeks for 3-6 cycles

Focal Therapy

Participants undergo additional cryotherapy and/or laser therapy for tumor consolidation

Up to 5 years as needed

Every 4-8 weeks or longer intervals

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, every 6 months for 2 years, then annually for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cryosurgery
• Cyclosporine
• Etoposide
• Laser Therapy
• Vincristine sulfate

Trial Overview The study is testing if combining chemotherapy (carboplatin, etoposide, vincristine) with cyclosporine followed by cryotherapy or laser therapy can effectively treat retinoblastoma. Cyclosporine may help reduce the tumor's resistance to chemotherapy.

How Is the Trial Designed?

Group I: CEV Chemo + Cyclosporine & Focal Therapy Experimental Treatment 7 Interventions

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.

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?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Terry Fox Foundation

Collaborator

Trials

8

Recruited

4,400+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11226919/

Retinoblastoma: An update on genetic origin, classification ... The clinical trial that utilized periocular administration of carboplatin, etoposide, and vincristine in combination for six months completed the phase-4 trial ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4399117/

Retinoblastoma: Achieving new standards with methods of ... Second malignant neoplasms following chemoreduction with carboplatin, etoposide, and vincristine in 245 patients with intraocular retinoblastoma. Pediatr ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00110110

Combination Chemotherapy and Cyclosporine Followed ... PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with cyclosporine followed by cryotherapy and/or laser therapy works ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024088753

Retinoblastoma: An update on genetic origin, classification ... The clinical trial that utilized periocular administration of carboplatin, etoposide, and vincristine in combination for six months completed ...

5. jamanetwork.com jamanetwork.com/journals/jamaophthalmology/fullarticle/415478

Comparison of Retinoblastoma Reduction for ... Shields et al reported 100% and 78% ocular salvage rates when a chemotherapeutic regimen consisting of a combination of carboplatin, vincristine, and etoposide ...

6. researchgate.net researchgate.net/publication/51557154_Second_malignant_neoplasms_following_chemoreduction_with_carboplatin_etoposide_and_vincristine_in_245_patients_with_intraocular_retinoblastoma

Second malignant neoplasms following chemoreduction ... One study has suggested that chemoreduction with vincristine, etoposide and carboplatin (VEC) may not lead to more leukemia cases, however mean ...