What is the mechanism of action of this treatment?

The most common treatments for Osteosarcoma include chemotherapy agents like methotrexate, cisplatin, and doxorubicin, which work by damaging the DNA of cancer cells, thereby inhibiting their ability to replicate and grow. Targeted therapies, such as monoclonal antibodies like Natalizumab, aim to interfere with specific molecules involved in tumor growth and immune evasion. Natalizumab targets alpha-4 integrin, reducing leukocyte adhesion and migration, which can potentially limit the tumor's ability to recruit immune cells that aid in its growth and spread. This is crucial for Osteosarcoma patients as it can help in controlling the metastatic spread of the disease and improve overall treatment outcomes.

What side effects are associated with this type of intervention?

Common treatments for osteosarcoma include chemotherapy agents like methotrexate, cisplatin, and doxorubicin, which are associated with side effects such as neutropenia, mucositis, nausea, vomiting, and anemia. Monoclonal antibodies, such as Natalizumab, which target alpha-4 integrin to reduce leukocyte adhesion and migration, are being studied for their safety and tolerability. Side effects of monoclonal antibodies can include infusion reactions, increased risk of infections, and potential reactivation of latent viruses. Overall, the side effects vary widely depending on the specific agent used.

What prior FDA approvals exist?

There is limited information on FDA-approved monoclonal antibodies specifically targeting alpha-4 integrin for the treatment of Osteosarcoma. Historically, the treatment of Osteosarcoma has primarily involved surgical resection and chemotherapy agents such as methotrexate, doxorubicin, and cisplatin. While monoclonal antibodies and other targeted therapies are being explored in clinical trials, including the use of Natalizumab, there have not been significant FDA approvals in this specific category for Osteosarcoma to date.

What other types of research exist?

A promising novel alternative to Natalizumab for osteosarcoma patients is the novel ADC targeting CSPG4-expressing melanoma, which could potentially be adapted for osteosarcoma due to its tumor-selective expression. Additionally, intetumumab (CNTO 95), an anti-αv integrin monoclonal antibody, has shown efficacy in enhancing radiation therapy and reducing metastasis in cancer models, which may be beneficial for osteosarcoma treatment.

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Monoclonal Antibodies

Natalizumab for Metastatic Osteosarcoma

Phase 1 & 2

Recruiting

Led By Kristen VanHeyst, DO

Research Sponsored by Case Comprehensive Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects must have measurable pulmonary disease per RECIST 1.1 documented by clinical, radiographic and histologic criteria, and have progressed, relapsed or become refractory to conventional therapy

Subjects must have a performance status corresponding to a Karnofsky ≥ 50% for participants > 16 years of age and Lansky ≥ 60 for participants ≤ 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score

Must not have

Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, liver failure, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Participants who have or have had progressive multifocal leukoencephalopathy (PML)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Natalizumab may cause allergic reactions similar to compounds of its class. There's also a risk of infection due to immune system suppression. Specific side effects are not listed but will relate to the drug’s impact on organ systems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My lung disease can be measured and has not improved with standard treatments.

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I can do most activities myself, even if I use a wheelchair.

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My bilirubin levels are within the normal range for my age.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have or had a brain infection called PML.

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I am not pregnant or breastfeeding.

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I am not HIV-positive or on HIV treatment.

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I am a woman able to have children and have a negative pregnancy test.

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I am currently taking medication to suppress my immune system.

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My lung cancer that has spread can be fully removed with surgery.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dosing limiting toxicity

Secondary study objectives

Clinical benefit rate

Overall survival measured in months

Side effects data

From 2011 Phase 4 trial • 19 Patients • NCT01144052

44%

Injection site reaction

33%

Infection

100%

80%

60%

40%

20%

Study treatment Arm

Interferon-beta-1b

Natalizumab

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Phase I: NatalizumabExperimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Natalizumab

2003

Completed Phase 4

~5310

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Osteosarcoma include chemotherapy agents like methotrexate, cisplatin, and doxorubicin, which work by damaging the DNA of cancer cells, thereby inhibiting their ability to replicate and grow. Targeted therapies, such as monoclonal antibodies like Natalizumab, aim to interfere with specific molecules involved in tumor growth and immune evasion. Natalizumab targets alpha-4 integrin, reducing leukocyte adhesion and migration, which can potentially limit the tumor's ability to recruit immune cells that aid in its growth and spread. This is crucial for Osteosarcoma patients as it can help in controlling the metastatic spread of the disease and improve overall treatment outcomes.