Combination Chemotherapy + Stem Cell Transplant/Radiation for Retinoblastoma

No longer recruiting at 81 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Disqualifiers: Prior chemotherapy, Prior radiotherapy, 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: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy, stem cell transplant, and radiation to evaluate their effectiveness in treating children with extraocular retinoblastoma, a type of eye cancer that has spread beyond the eye. The goal is to determine if this treatment can effectively stop cancer cell growth and potentially kill them. Participants must have confirmed extraocular retinoblastoma and should not have received chemotherapy or radiation for this type of cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol 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 treatments used in this trial are safe for humans.

Carboplatin causes few side effects, especially when doses are adjusted for young patients. It is considered safe and effective for treating high-risk retinoblastoma, with some studies reporting minimal side effects. Cisplatin is effective but can cause nerve damage at high doses. However, studies indicate good results when doses are carefully controlled. Etoposide is generally safe, with few reports of harm to the entire body. Long-term side effects are rare, making it a good option.

Thiotepa has been tested in high doses and shows promising survival rates, but monitoring for any health changes during treatment is important. Lastly, Vincristine Sulfate is FDA-approved for neuroblastoma and has been used successfully for retinoblastoma. Studies report no issues with its administration, indicating a good safety profile.

Overall, these treatments are generally well-tolerated. However, monitoring for side effects remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for retinoblastoma because it uniquely blends chemotherapy, autologous stem cell transplantation, and targeted radiotherapy. Unlike standard treatments that primarily rely on chemotherapy or radiotherapy alone, this regimen uses a robust lineup of chemotherapy drugs like carboplatin, cisplatin, etoposide, thiotepa, and vincristine sulfate to aggressively target cancer cells. Additionally, the inclusion of autologous stem cell infusion allows patients to recover their blood cell counts more quickly after intensive chemotherapy, potentially improving outcomes for those with more advanced stages of the disease. This multifaceted approach aims to enhance treatment effectiveness while minimizing long-term side effects, making it a promising option for children with retinoblastoma.

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

In this trial, participants will receive a combination of treatments, including chemotherapy and radiotherapy, to treat retinoblastoma. Previous studies have shown that carboplatin and etoposide are 85% effective in treating extraocular retinoblastoma, with many patients experiencing full or partial recovery. Cisplatin, another drug used in this trial, has successfully treated advanced retinoblastoma when combined with other treatments. Vincristine sulfate, especially when combined with drugs like etoposide and carboplatin, helps prevent cancer from spreading after eye removal. Thiotepa, also part of this trial, has been associated with better survival rates. Overall, these drugs, when used together in this trial, aim to stop tumors from growing by preventing cancer cells from multiplying or destroying them. ^{1 2 5 6 7}

Who Is on the Research Team?

Ira J Dunkel

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients with extraocular retinoblastoma, a type of eye cancer that has spread outside the eye. They should be in good physical condition (ECOG score 0-2), have not received prior treatment for this condition, and meet specific blood count and organ function criteria. Consent from patients or guardians is required.

Inclusion Criteria

All patients and/or their parents or legal guardians must sign a written informed consent

All institutional, FDA, and NCI requirements for human studies must be met

Total bilirubin =< 1.5 times upper limit of normal (ULN)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Patients receive vincristine, cisplatin, cyclophosphamide, etoposide, and filgrastim. Treatment repeats every 21 days for up to 4 courses.

12 weeks

4 visits (in-person)

Stem Cell Harvesting

Peripheral blood stem cells or bone marrow cells are collected after at least 1 course of induction chemotherapy.

1 week

High-Dose Consolidation Chemotherapy

Patients receive carboplatin, thiotepa, and etoposide.

1 week

Autologous Stem Cell Infusion

Patients undergo autologous stem cell infusion and receive filgrastim until blood counts recover.

1 week

Radiotherapy

Patients undergo radiotherapy to sites initially involved based on response.

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment.

1 year

Every 3 months for 1 year, then annually for 9 years

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Bone Marrow Transplantation
• Autologous Hematopoietic Stem Cell Transplantation
• Carboplatin
• Cisplatin
• Etoposide
• Filgrastim
• In Vitro-Treated Peripheral Blood Stem Cell Transplantation
• Radiation Therapy
• Thiotepa
• Vincristine Sulfate

Trial Overview The study tests how well combination chemotherapy works with autologous stem cell transplant and/or radiation therapy to treat these patients. The process involves using drugs to stop tumor growth, collecting the patient's own stem cells, giving more chemo to prepare for transplanting these cells back into the patient, followed by possible radiation therapy.

How Is the Trial Designed?

Group I: Treatment (chemotherapy, radiotherapy, autologous SCI) Experimental Treatment 11 Interventions

INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover. CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV. AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover. RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.

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?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7384850/

Comparison of the therapeutic effects of lobaplatin and ... In the present study, it was confirmed that carboplatin and lobaplatin both exert antitumor effects on RB by inhibiting the E2F1 signaling pathway and that ...

2. nature.com nature.com/articles/s41416-024-02728-1

Utility of carboplatin therapeutic drug monitoring for the ... The current study highlights the benefit of delivering carboplatin to infants with retinoblastoma using a real-time TDM approach. This avoids ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2825162

Three vs 6 Cycles of Chemotherapy for High-Risk ... In the current study, the 5-year disease-free survival and overall survival rates for the 3-cycle postenucleation chemotherapy group were 90.4% ...

4. cancertherapyadvisor.com cancertherapyadvisor.com/news/combo-safe-effective-high-risk-intraocular-retinoblastoma/

Combo Appears Safe, Effective in High-Risk Intraocular ... Carboplatin plus etoposide, with or without focal treatments, may be safe and effective for patients with high-risk intraocular ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9792108/

Spotlight on Targeted Chemotherapy in Retinoblastoma According to a rodent study, topotecan with carboplatin effectively stopped the progression of RB compared to vincristine, carboplatin, and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/10519590/

A phase I/II study of subconjunctival carboplatin for ... Conclusions: Subconjunctival carboplatin as used in this protocol is effective for intraocular retinoblastoma. It appears to be safe, but additional study and ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2162098924000562

Update on chemotherapy modalities for retinoblastoma In 2012, Munier et al. reported a notable safety profile and high success rate for IvitC in controlling tumors with vitreous seeding and minimal side effects, ...