LY3295668 Erbumine for Neuroblastoma

Recruiting at 44 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

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

Compensation: Varies

Number of Visits: 28

Duration: 8 weeks

71 Participants Needed

Trial Summary

What is the purpose of this trial?

The reason for this study is to see if the study drug LY3295668 erbumine is safe in participants with relapsed/refractory neuroblastoma.

Do I need to stop my current medications for the trial?

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.

What data supports the effectiveness of the drug LY3295668 Erbumine for treating neuroblastoma?

Research shows that combining topotecan with cyclophosphamide has been used effectively in treating neuroblastoma, with studies indicating that this combination can help manage the disease and improve outcomes in high-risk patients. ^{1 2 3 4 5}

What safety data exists for LY3295668 Erbumine and related treatments?

The research does not provide specific safety data for LY3295668 Erbumine or the related treatments mentioned for neuroblastoma or other conditions. ^{6 7 8 9 10}

What makes the drug LY3295668 Erbumine for neuroblastoma unique?

The drug LY3295668 Erbumine for neuroblastoma is unique because it combines LY3295668 Erbumine with cyclophosphamide and topotecan, which are known for their effectiveness in treating resistant neuroblastoma with minimal risk to major organs, potentially enhancing the immune response to other therapies. ^{1 3 11 12 13}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for people with neuroblastoma that has come back or didn't respond to treatment. They must have active cancer in bone, marrow, or soft tissue and be able to provide a tissue sample. Participants need to swallow pills but can't join if they've had certain transplants, untreated brain/spinal tumors, serious diseases besides cancer, absorption issues, prior aurora kinase inhibitor use, allergies to the drug, or symptomatic HIV/hepatitis.

Inclusion Criteria

My neuroblastoma has returned or didn't respond to treatment, and I can provide a tissue sample.

I can swallow pills.

Exclusion Criteria

I do not have any conditions that affect how my body absorbs medication.

I do not have any serious active diseases other than neuroblastoma.

I do not have untreated cancer in my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LY3295668 Erbumine, with some groups also receiving Topotecan and Cyclophosphamide

8 weeks

Multiple visits per cycle (28-day cycles)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Estimated up to 5 years

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Estimated up to 6 years

Treatment Details

Interventions

• Cyclophosphamide
• LY3295668 Erbumine
• Topotecan

Trial Overview The study is testing LY3295668 erbumine's safety for relapsed/refractory neuroblastoma patients. It involves taking this new medication alongside standard drugs Cyclophosphamide and Topotecan to see how well it works and what side effects occur.

Participant Groups

Group I: LY3295668 Erbumine Expansion Experimental Treatment 1 Intervention

LY3295668 Erbumine given orally.

Group II: LY3295668 Erbumine Escalation Experimental Treatment 1 Intervention

LY3295668 Erbumine given orally.

Group III: LY3295668 Erbumine + Topotecan + Cyclophosphamide Expansion Experimental Treatment 3 Interventions

LY3295668 Erbumine given orally and topotecan and cyclophosphamide given IV.

Group IV: LY3295668 Erbumine + Topotecan + Cyclophosphamide Escalation Experimental Treatment 3 Interventions

LY3295668 Erbumine given orally and topotecan and cyclophosphamide given intravenously (IV).

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Innovative Therapies for Children with Cancer in Europe (ITCC)

Collaborator

Trials

1

Recruited

70+

New Approaches to Neuroblastoma Therapy Consortium (NANT)

Collaborator

Trials

1

Recruited

70+

Findings from Research

In a phase II trial involving 119 children with relapsed/refractory neuroblastoma, the combination of topotecan and cyclophosphamide (TOPO/CTX) showed a higher response rate (32%) compared to single-agent topotecan (19%), indicating that TOPO/CTX may be more effective in achieving initial responses.

While TOPO/CTX resulted in significantly better progression-free survival (PFS), there was no difference in overall survival (OS) between the two treatments after adjusting for subsequent therapies, suggesting that while TOPO/CTX may delay disease progression, it does not necessarily improve long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II randomized comparison of topotecan plus cyclophosphamide versus topotecan alone in children with recurrent or refractory neuroblastoma: a Children's Oncology Group study. London, WB., Frantz, CN., Campbell, LA., et al.[2022]

An optimized liposomal formulation of topotecan, specifically using sphingomyelin/cholesterol (SM/Chol), showed significantly better drug retention and tolerability in mice compared to the previously used DSPC/cholesterol formulation.

This new formulation resulted in a 10-fold increase in plasma half-life and a 1000-fold increase in drug exposure over 24 hours, although it only modestly increased the lifespan of mice with neuroblastoma, indicating that further optimization may be needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of liposomal topotecan for use in treating neuroblastoma. Chernov, L., Deyell, RJ., Anantha, M., et al.[2022]

Topotecan, used in a myeloablative regimen with thiotepa and carboplatin, showed promising efficacy in treating poor-prognosis tumors, particularly in neuroblastoma and brain tumors, with a follow-up of up to 32 months revealing significant event-free survival rates.

The treatment was associated with manageable toxicities, although severe mucositis and other complications were noted, indicating that while the regimen is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults. Kushner, BH., Cheung, NK., Kramer, K., et al.[2013]

In a study of 107 high-risk neuroblastoma patients, an induction regimen combining topotecan and cyclophosphamide resulted in favorable treatment responses, with no patients experiencing stable disease or progression after the fifth cycle.

The treatment was well tolerated, with febrile neutropenia being the most common side effect, indicating that this regimen could be a safe and effective option for managing high-risk neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes and prognostic factors to predict treatment response in high risk neuroblastoma patients receiving topotecan and cyclophosphamide containing induction regimen: a prospective multicenter study. Rujkijyanont, P., Photia, A., Traivaree, C., et al.[2020]

Topiramate is effective in reducing seizure frequency by 35-47% at a dose of 400 mg/day for patients with partial-onset seizures, and it can also be used alone for this type of seizure.

While topiramate has a good safety profile with no serious toxicity reported, common side effects include psychomotor slowing, which often resolves with time or dosage adjustments; 11-28% of patients may stop taking it due to side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical studies of topiramate. Faught, E.[2019]

In a Phase 2 trial involving 55 pediatric patients with epilepsy, lacosamide (LCM) was found to be safe and well-tolerated, with no significant worsening of generalized seizures observed during treatment.

While there were trends toward improvement in seizure frequency, particularly in various seizure types, the overall efficacy in reducing seizure counts was not statistically significant, indicating the need for further studies to evaluate its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and efficacy of adjunctive lacosamide in pediatric patients with epilepsy syndromes associated with generalized seizures: Phase 2, open-label exploratory trial. Auvin, S., Arzimanoglou, A., Beller, C., et al.[2023]

FTY720 shows potent anti-cancer activity against neuroblastoma (NB) in preclinical models, effectively inducing cell death and inhibiting tumor growth, especially when combined with the chemotherapy drug topotecan.

The mechanism of action for FTY720 involves the inhibition of sphingosine kinase 2 and the alteration of sphingolipid levels, leading to a unique, caspase-independent cell death pathway that may enhance treatment strategies for advanced NB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FTY720 inhibits tumor growth and enhances the tumor-suppressive effect of topotecan in neuroblastoma by interfering with the sphingolipid signaling pathway. Li, MH., Hla, T., Ferrer, F.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Camptothecin analogs (irinotecan or topotecan) plus high-dose cyclophosphamide as preparative regimens for antibody-based immunotherapy in resistant neuroblastoma. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II randomized comparison of topotecan plus cyclophosphamide versus topotecan alone in children with recurrent or refractory neuroblastoma: a Children's Oncology Group study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Optimization of liposomal topotecan for use in treating neuroblastoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Clinical outcomes and prognostic factors to predict treatment response in high risk neuroblastoma patients receiving topotecan and cyclophosphamide containing induction regimen: a prospective multicenter study. [2020]

6. Spain pubmed.ncbi.nlm.nih.gov

Clinical studies of topiramate. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and efficacy of adjunctive lacosamide in pediatric patients with epilepsy syndromes associated with generalized seizures: Phase 2, open-label exploratory trial. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of adjunctive lacosamide in a pediatric population with focal seizures - An open-label trial. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

A study of topiramate pharmacokinetics and tolerability in children with epilepsy. [2019]

10. India pubmed.ncbi.nlm.nih.gov

Efficacy of Topiramate as an add-on drug in seizures in Indian children--an observational study. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

FTY720 inhibits tumor growth and enhances the tumor-suppressive effect of topotecan in neuroblastoma by interfering with the sphingolipid signaling pathway. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Murine neuroblastoma: further evaluation of the C1300 model with single antitumor agents. [2016]

13. United States pubmed.ncbi.nlm.nih.gov

Studies and characterization of a murine neuroblastoma model. [2019]