Natalizumab for Metastatic Osteosarcoma

Recruiting in Palo Alto (17 mi)

Overseen by Kristen VanHeyst, DO

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Case Comprehensive Cancer Center

No Placebo Group

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if Natalizumab, a drug that changes how the immune system works, can help young patients with a specific type of lung-spread bone cancer that hasn't responded to other treatments.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot be on immunosuppressive therapy or other investigational agents while participating.

What data supports the idea that Natalizumab for Metastatic Osteosarcoma is an effective treatment?

The available research does not provide specific data supporting the effectiveness of Natalizumab for Metastatic Osteosarcoma. Instead, it discusses other treatments like tyrosine kinase inhibitors and ErbB-targeted therapies, which are being explored for this condition. These alternatives are being prioritized for clinical trials due to the lack of progress in improving survival rates for metastatic osteosarcoma with existing treatments. ^{1 2 3 4 5}

What safety data exists for Natalizumab (Tysabri)?

Natalizumab, also known as Tysabri, has been studied for its safety in multiple sclerosis (MS) and Crohn's disease. It has been associated with progressive multifocal leukoencephalopathy (PML), a serious brain infection, in some patients. The drug is generally well tolerated but carries an increased risk of infections, such as influenza. Due to the risk of PML, its use is restricted under the TOUCH program in the USA. Safety data from the STRATA MS Study indicates long-term safety over 240 weeks. Natalizumab was reapproved for relapsing forms of MS after initial concerns about PML. ^{6 7 8 9 10}

Is the drug Natalizumab a promising treatment for metastatic osteosarcoma?

Based on the provided research articles, there is no specific mention of Natalizumab as a promising treatment for metastatic osteosarcoma. The articles discuss other potential treatments and targets, but Natalizumab is not highlighted among them. ^{4 11 12 13 14}

Research Team

Kristen VanHeyst, DO

Principal Investigator

University Hospitals Cleveland Medical Center

Eligibility Criteria

This trial is for children and young adults with a type of bone cancer that has spread to the lungs (pulmonary metastatic osteosarcoma) and hasn't improved with standard treatments. Participants need normal heart, liver, and marrow function, no severe ongoing illnesses or infections, not be on immunosuppressive therapy or other investigational drugs, and agree to use contraception if applicable.

Inclusion Criteria

My liver is working well.

Peripheral absolute neutrophil count (ANC) ≥ 750/mcL

My organ and bone marrow functions are normal.

Exclusion Criteria

I have side effects from previous treatments, but they are mild except for hair loss, lack of appetite, bone, and tumor pain.

I do not have any severe illnesses that would stop me from following the study's requirements.

Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Treatment Details

Interventions

• Natalizumab (Monoclonal Antibodies)

Trial Overview The study tests Natalizumab's safety and how well it works in patients with pulmonary metastatic osteosarcoma. It aims to see if this drug can improve survival rates in those who have not responded well to conventional therapies.

Participant Groups

Group I: Phase I: Natalizumab Experimental Treatment 1 Intervention

Traditional 3+3 design escalation of Natalizumab at a weight-based dosing 2mg/kg not to exceed a maximum dose of 300mg Phase II treatment to continue if the participant has Complete Response (CR), Partial Response (PR) or Stable Disease (SD) of pOS as defined by RECIST 1.1 criteria after every 3 cycles after the first 6 cycles but not beyond 24 cycles. If the participant has progressive disease after 6 cycles, they will be removed from the study.

Natalizumab is already approved in Canada, Japan, Switzerland for the following indications:

Approved in Canada as Tysabri for:

• Multiple sclerosis
• Crohn's disease

Approved in Japan as Tysabri for:

• Multiple sclerosis

Approved in Switzerland as Tysabri for:

• Multiple sclerosis
• Crohn's disease

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Dr. Gary K. Schwartz

Case Comprehensive Cancer Center

Chief Executive Officer since 2023

MD, FASCO

Dr. Nathan Berger

Case Comprehensive Cancer Center

Chief Medical Officer since 2020

MD

Findings from Research

In a study of 45 patients with relapsing-remitting multiple sclerosis (RRMS) who switched to natalizumab after inadequate response to other treatments, 62% showed no signs of disease activity after 44 weeks, indicating its effectiveness in controlling the disease.

Approximately 29% of patients experienced significant improvements in disability status, as measured by the Expanded Disability Status Scale (EDSS), and about 30% showed enhanced walking speed, suggesting that natalizumab can rapidly improve both disability and ambulation in patients with high disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis. Belachew, S., Phan-Ba, R., Bartholomé, E., et al.[2021]

The methotrexate-bisphosphonate conjugate significantly inhibits the growth of human osteosarcoma MG-63 cells, with a notable decrease in cell survival observed at concentrations of 2000 mg/ml or higher over 24 to 96 hours.

This conjugate effectively induces apoptosis in MG-63 cells, as evidenced by various assays including TUNEL and flow cytometry, making it a promising candidate for targeted therapy in osteosarcoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted antiosteosarcoma methotrexate-bisphosphonate conjugate induces apoptosis of osteosarcoma cells in vitro. Yang, XN., Zeng, JC., Song, YC., et al.[2014]

References

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

Role of TKI for Metastatic Osteogenic Sarcoma. [2021]

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

LacZ transgene expression in the subcutaneous Dunn/LM8 osteosarcoma mouse model allows for the identification of micrometastasis. [2011]

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

Real-world experience of tyrosine kinase inhibitors in children, adolescents and adults with relapsed or refractory bone tumours: A Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) study. [2023]

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

Charting a path for prioritization of novel agents for clinical trials in osteosarcoma: A report from the Children's Oncology Group New Agents for Osteosarcoma Task Force. [2022]

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

Advanced development of ErbB family-targeted therapies in osteosarcoma treatment. [2020]

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

Long-term safety and effectiveness of natalizumab redosing and treatment in the STRATA MS Study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Natalizumab for the treatment of Crohn's disease. [2015]

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

Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Impact of natalizumab on patient-reported outcomes in a clinical practice setting: a cross-sectional survey. [2021]

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

Pharmacological properties, toxicology and scientific rationale for the use of natalizumab (Tysabri) in inflammatory diseases. [2020]

11. Italy pubmed.ncbi.nlm.nih.gov

Targeted antiosteosarcoma methotrexate-bisphosphonate conjugate induces apoptosis of osteosarcoma cells in vitro. [2014]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Identification of therapeutic targets for osteosarcoma by integrating single-cell RNA sequencing and network pharmacology. [2023]

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

Antimetastatic activity of honokiol in osteosarcoma. [2012]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Immunoconjugates for Osteosarcoma Therapy: Preclinical Experiences and Future Perspectives. [2020]