Sorafenib + Cyclophosphamide/Topotecan for Neuroblastoma

(N2013-02 Trial)

Not currently recruiting at 11 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: New Approaches to Neuroblastoma Therapy Consortium

Must not be taking: Anticoagulants, Antihypertensives, Antiarrhythmics, Enzyme inducers

Disqualifiers: Pregnancy, Infection, Allogeneic transplant, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days per course, repeated over 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest high dose of sorafenib, a cancer treatment drug, that can be combined with cyclophosphamide and topotecan to treat neuroblastoma. Neuroblastoma primarily affects children and often returns or resists treatment. Researchers seek to determine if adding sorafenib enhances treatment effectiveness. This study is open to individuals under 30 with a confirmed diagnosis of high-risk neuroblastoma that has either recurred or not responded well to initial treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking cancer research.

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

The trial protocol does not specify if you need to stop all current medications, but you cannot take certain medications like anti-cancer agents, investigational drugs, enzyme inducers, anti-coagulation, anti-arrhythmic, or anti-hypertensive medications during the study. It's best to discuss your current medications with the study team.

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

Research shows that sorafenib, when combined with cyclophosphamide and topotecan, might have manageable side effects for patients with neuroblastoma. Earlier studies have shown that sorafenib can reduce the size of neuroblastoma tumors and enhance immune cells to help fight the cancer. However, this specific combination of the three drugs is being tested in humans for the first time, so researchers are still determining the safest dosage of sorafenib with cyclophosphamide and topotecan.

Sorafenib is a drug that can stop tumors from growing by preventing the formation of new blood vessels they need. A review found that about half of children using these types of drugs alone experienced serious side effects. This combination therapy aims to find a safe way to use sorafenib with the other two drugs, potentially balancing effectiveness with safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Sorafenib, Cyclophosphamide, and Topotecan for treating neuroblastoma because it offers a novel approach compared to current therapies. Sorafenib is a targeted therapy that inhibits specific proteins involved in cancer cell growth, which is different from the standard chemotherapy options that broadly attack rapidly dividing cells. This targeted action may potentially reduce side effects and improve outcomes when used alongside traditional drugs like Cyclophosphamide and Topotecan. This combination also includes growth factor support, which could help manage side effects and enhance recovery, making the treatment more tolerable for young patients.

What evidence suggests that this treatment might be an effective treatment for neuroblastoma?

Research has shown that adding sorafenib to cyclophosphamide and topotecan might enhance treatment effectiveness against neuroblastoma. Lab studies demonstrated that sorafenib shrinks neuroblastoma tumors and appears to activate immune cells to fight the tumors more effectively. This trial will test the combination of sorafenib, cyclophosphamide, and topotecan together for the first time. Early lab results are promising, and scientists hope this combination could improve treatment outcomes for patients with neuroblastoma that is difficult to treat or has recurred after treatment. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for patients under 30 with high-risk neuroblastoma that's come back or didn't respond to treatment. They should have a certain level of bone marrow activity, no recent other cancer treatments, and be able to perform daily activities at least half the time. Not eligible if pregnant, breastfeeding, had an allogeneic transplant, uncontrolled infections or certain heart conditions.

Inclusion Criteria

Serum albumin > 2.5 g/dl

I am not on blood thinners.

My cancer has come back, hasn't responded well, or still exists after initial treatment.

Exclusion Criteria

I or my close family had blood clots before 40, but only if not caused by a central line.

Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events

I do not have any active or uncontrolled infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sorafenib in combination with cyclophosphamide and topotecan to determine the maximum tolerated dose

5 days per course, repeated over 2 years

Multiple visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Sorafenib
• Topotecan

Trial Overview The study tests combining sorafenib with cyclophosphamide and topotecan in children and young adults with relapsed/refractory neuroblastoma. It aims to find the highest safe dose of sorafenib when used with these drugs for this specific condition.

How Is the Trial Designed?

Group I: Sorafenib and Cyclophosphamide/Topotecan Experimental Treatment 3 Interventions

Sorafenib and Cyclophosphamide/Topotecan with growth factor support.

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?

New Approaches to Neuroblastoma Therapy Consortium

Lead Sponsor

Trials

19

Recruited

1,700+

Cook Children's Health Care System

Collaborator

Trials

11

Recruited

5,001,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Children's Healthcare of Atlanta

Collaborator

Trials

172

Recruited

108,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

The Hospital for Sick Children

Collaborator

Trials

724

Recruited

6,969,000+

Lucile Packard Children's Hospital

Collaborator

Trials

16

Recruited

2,800+

Published Research Related to This Trial

In a Phase II trial involving 25 children with advanced neuroblastoma, the combination of topotecan, vincristine, and doxorubicin showed a promising overall response rate of 64%, with 4 complete responses and 12 partial responses.

The treatment was generally well tolerated, with limited toxicity primarily affecting the hematopoietic system, and only one patient experiencing dose-limiting Grade 4 liver toxicity, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of topotecan with vincristine and doxorubicin in children with recurrent/refractory neuroblastoma. Garaventa, A., Luksch, R., Biasotti, S., et al.[2020]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02298348

Sorafenib and Cyclophosphamide/Topotecan in Patients ... In the laboratory, sorafenib appears to make neuroblastoma tumors smaller, and in addition can help immune cells to be more active in attacking tumors and ...

2. withpower.com withpower.com/trial/phase-1-neuroblastoma-3-2015-2f369

Sorafenib + Cyclophosphamide/Topotecan for ... Adding sorafenib to cyclophosphamide and topotecan may increase the effectiveness of this combination. The investigators first need to find out the highest dose ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5649635/

Emerging and investigational therapies for neuroblastoma Specifically, nine of seventeen patients (52.9%) treated with dinutuximab and chemotherapy had a clinical response, and five (19.4%) achieved a complete ...

4. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/neuroblastoma

UCSF Neuroblastoma Clinical Trials — San Francisco Bay Area Adding sorafenib to cyclophosphamide and topotecan may increase the effectiveness of this combination. The investigators first need to find ...

5. med.stanford.edu med.stanford.edu/mosslab/research/clinicaltrial?start=1480

Clinical Trial | Moss Lab | Stanford Medicine Adding sorafenib to cyclophosphamide and topotecan may increase the effectiveness of this combination. The investigators first need to find out the highest ...

6. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT02298348

Sorafenib and Cyclophosphamide/Topotecan in Patients With ... In the laboratory, sorafenib appears to make neuroblastoma tumors smaller, and in addition can help immune cells to be more active in attacking ...

7. mdpi.com mdpi.com/2072-6694/14/21/5315

Safety of Anti-Angiogenic Drugs in Pediatric Patients with ... This systematic review and meta-analysis reported that one out of two pediatric patients using anti-angiogenic drugs in monotherapy experienced a serious ...