Pulmonary Metastatic Osteosarcoma (pOS)Phase 1/2NCT03811886
Natalizumab in Recurrent, Refractory or Progressive Pulmonary Metastatic Osteosarcoma
A Phase 1/2 study testing Natalizumab in people with Pulmonary Metastatic Osteosarcoma (pOS), run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of Natalizumab in children, adolescent and young adult patients with pulmonary metastatic osteosarcoma (pOS) and to assess clinical response associated with this treatment as well as overall survival. Read more about this study
- Who is it for?
- Ages 5 to 30 years
- Conditions the study is for
- Pulmonary Metastatic Osteosarcoma (pOS)
- What is being tested?
- Natalizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2024to 1 Oct 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subjects may be male or female and must be equal to or greater than 5 years of age but less than or equal to 30 years of age at the time of enrollment. No large studies have evaluated the use of Natalizumab in younger pediatric patients, and Natalizumab is currently only FDA approved for adult use; for this reason, children younger than 5 years of age are excluded from this study.
- Subjects must have histologic verification of pOS.
- Subjects must have measurable pulmonary disease or pleural disease per RECIST 1.1 documented by clinical, radiographic and histologic criteria, and have progressed, relapsed or become refractory to conventional therapy.
- -- Subjects despite having peripheral diseases elsewhere outside of pulmonary disease or pleural disease, may be eligible:
- if these diseases have failed upfront standard therapy AND
- one or two salvage therapies
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- Subjects must have recovered from the acute toxic effects with ≤ Grade 1 as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 of all prior chemotherapy and immunotherapy with the exception of alopecia, anorexia, bone pain, and tumor pain prior to entering this study.
- Myelosuppressive chemotherapy: Must have adequate recovery of counts from previous treatment prior to entry onto this study.
- Monoclonal antibodies: At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody.
- 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.
- Subjects must have normal organ and marrow function as defined below:
- Adequate bone marrow function defined as:
- Peripheral absolute neutrophil count (ANC) ≥ 750/mcL
- Platelet count ≥ 75,000/mcL (transfusion independent)
- Hemoglobin ≥ 8.0 g/dL (may receive packed red blood cell transfusions)
- Adequate liver function defined as:
- Total bilirubin ≤ 1.5 times the upper limit of normal for age
- AST (SGOT) and ALT (SGPT) 2.5 X institutional upper limit of normal
- Serum albumin > 2 g/dL
- Adequate cardiac function defined as:
- Ejection fraction of ≥ 50% by echocardiogram
- Subjects must have the ability to understand and the willingness to sign a written informed consent document if ≥ 18 years of age and an assent document if < 18 years of age. If < 7 years of age, no assent document is required.
Who cannot join
- The presence of any of the following will exclude a subject from study enrollment.
- Patients with evidence of osteosarcoma outside of the lungs or pleura.
- Ongoing prior treatment toxicities > Grade 1 according to NCI CTCAE Version 5.0 with the exception of alopecia, anorexia, bone pain and tumor pain.
- Subjects receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Natalizumab.
- Subjects currently on immunosuppressive therapy.
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- 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.
- Pregnant or breastfeeding women are excluded from this study because Natalizumab crosses the placenta and can increase the risk of spontaneous abortion. There is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with Natalizumab, therefore breastfeeding should be discontinued if the mother is treated with Natalizumab.
- Female participants of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
- 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.
- HIV-positive subjects and HIV-positive subjects on antiretroviral therapy are ineligible because of the risk for developing a lethal infection when treated with immunosuppressive therapy.
- Participants who have or have had progressive multifocal leukoencephalopathy (PML).
- Participants whose pulmonary metastatic disease or pleural disease can be completely surgically resected.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
About this study
Official title: A Phase I/II Study of Natalizumab as a Single Agent in Children, Adolescents and Young Adults With Recurrent, Refractory or Progressive Pulmonary Metastatic Osteosarcoma
The purpose of this study is to evaluate the safety and tolerability of Natalizumab in children, adolescent and young adult patients with pulmonary metastatic osteosarcoma (pOS) and to assess clinical response associated with this treatment as well as overall survival.
Read the detailed description
This study is a single-arm, open-label, proof of concept clinical trial in children, adolescent and young adult patients with unresectable pOS that have progressed, relapsed or are refractory to standard systemic therapy.
All participants will receive the study therapy and there will be dose escalation in a traditional 3 + 3 design during the Phase I study of this trial.
In the Phase II study of the trial, treatment will continue if the subject has Complete Response (CR), Partial Response (PR) or Stable Disease (SD) of pOS after every 3 cycles after the first 6 cycles but not beyond 24 cycles, unless it is judged to be in his/her best interest.
Approximately 3-9 subjects will be enrolled in the phase I part and 10-12 in the phase II part of this trial. Participants will be followed for toxicity for 30 days after treatment has been discontinued or until one of the protocol-defined reasons
This study seeks to evaluate if Natalizumab can be used safely and effectively as immunotherapy in children, adolescent and young adult patients with pOS. Natalizumab is currently Food and Drug Administration (FDA) approved for the treatment of T-cell mediated autoimmune disorders The study team will evaluate the safety and tolerability of Natalizumab as well as the clinical response associated with Natalizumab treatment and evaluate overall survival.
- Conditions
- Pulmonary Metastatic Osteosarcoma (pOS)
- Being tested
- Natalizumab
- Keywords
- Natalizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NatalizumabDrug
Also called Tysabri
Natalizumab is an FDA approved monotherapy for treatment of relapsing forms of MS. It is also indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active CD who have had an inadequate response to, or intolerance of, conventional therapies and TNF-α inhibitors.
Traditional 3+3 escalation of Natalizumab at a weight-based dosing 2mg/kg not to exceed 300mg. If no subjects experience a dose limiting toxicity (DLT), 3 more subjects are enrolled at the next dose of 3mg/kg, not to exceed 300mg. If no subjects experience a DLT, 3 more subjects will be enrolled at the next and final dose of 4mg/kg, not to exceed 300mg.
Phase II will continue if the subject has Complete Response (CR), Partial Response (PR) or Stable Disease (SD) of pOS, defined by RECIST 1.1 criteria after every 3 cycles after the first 6 cycles but not beyond 24 cycles. If subject has progressive disease after cycle 6, they will be removed from the study.
| Study group | Role | What they receive |
|---|---|---|
| Phase I: Natalizumab | Experimental | 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. Receives: Drug: Natalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dosing limiting toxicity
Hematologic dose limiting toxicities: Grade 4 neutropenia or thrombocytopenia of > 7 days duration; or myelosuppression that causes a delay of > 8 weeks between treatment courses
Non-hematologic dose-limiting toxicities: Any Grade 4 non-hematologic toxicity attributable to Natalizumab with the specific exclusion of:
- Grade 4 nausea and vomiting responding to anti-emetics, alopecia, fatigue and drug related fever
- Grade 4 fever
- Any Grade 3 or greater neurologic toxicity
- Any Grade 3 or greater anaphylaxis
- Any Grade 2 or greater elevation in transaminases and bilirubin levels
- Any Grade 4 non-hematologic toxicities (excluding alopecia, nausea and vomiting) that do not resolve to ≤ Grade 1 by 8 weeks following the most recent dose of Natalizumab
Measured: 30 days after end of treatment (1 year)
Secondary outcomes (2)
Clinical benefit rate
Clinical benefit rate as defined by the number of participants that have Complete Response (CR), Partial Response (PR) or Stable Disease (SD) after 12 cycles
Measured: 1 year after start of treatment
Overall survival measured in months
Overall survival measured in months and summarized using Kaplan-Meier analysis. This will be calculated from the date of registration on-study to the dates of documented evidence of progression or death, up to 3 years
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2019
- Study start1 Dec 2024 (estimated)
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Oct 2026 (estimated)
Why it stopped: No accruals
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Metastatic Osteosarcoma (pOS)Studies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kristen VanHeyst, DO, Principal investigator, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03811886
- Sponsor's protocol ID
- CASE1718
- Status last verified
- Jan 2025
- First submitted
- 18 Jan 2019
- Last updated
- 15 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Natalizumab as a Single Agent in Children, Adolescents and Young Adults With Recurrent, Refractory or Progressive Pulmonary Metastatic Osteosarcoma
- ClinicalTrials.gov ID
- NCT03811886
- Acronym / sponsor ID
- CASE1718
- Conditions
- Pulmonary Metastatic Osteosarcoma (pOS)
- Keywords
- Natalizumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No accruals
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 1 Dec 2024 (estimated)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Oct 2026 (estimated)
- First posted
- 22 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and tolerability of Natalizumab in children, adolescent and young adult patients with pulmonary metastatic osteosarcoma (pOS) and to assess clinical response associated with this treatment as well as overall survival.
Detailed description
This study is a single-arm, open-label, proof of concept clinical trial in children, adolescent and young adult patients with unresectable pOS that have progressed, relapsed or are refractory to standard systemic therapy.
All participants will receive the study therapy and there will be dose escalation in a traditional 3 + 3 design during the Phase I study of this trial.
In the Phase II study of the trial, treatment will continue if the subject has Complete Response (CR), Partial Response (PR) or Stable Disease (SD) of pOS after every 3 cycles after the first 6 cycles but not beyond 24 cycles, unless it is judged to be in his/her best interest.
Approximately 3-9 subjects will be enrolled in the phase I part and 10-12 in the phase II part of this trial. Participants will be followed for toxicity for 30 days after treatment has been discontinued or until one of the protocol-defined reasons
This study seeks to evaluate if Natalizumab can be used safely and effectively as immunotherapy in children, adolescent and young adult patients with pOS. Natalizumab is currently Food and Drug Administration (FDA) approved for the treatment of T-cell mediated autoimmune disorders The study team will evaluate the safety and tolerability of Natalizumab as well as the clinical response associated with Natalizumab treatment and evaluate overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I: Natalizumab | Experimental | Drug: NatalizumabTraditional 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. |
Who may qualify
- Ages
- 5 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (22 listed)
- Subjects may be male or female and must be equal to or greater than 5 years of age but less than or equal to 30 years of age at the time of enrollment. No large studies have evaluated the use of Natalizumab in younger pediatric patients, and Natalizumab is currently only FDA approved for adult use; for this reason, children younger than 5 years of age are excluded from this study.
- Subjects must have histologic verification of pOS.
- Subjects must have measurable pulmonary disease or pleural disease per RECIST 1.1 documented by clinical, radiographic and histologic criteria, and have progressed, relapsed or become refractory to conventional therapy.
- -- Subjects despite having peripheral diseases elsewhere outside of pulmonary disease or pleural disease, may be eligible:
- Subjects must have recovered from the acute toxic effects with ≤ Grade 1 as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 of all prior chemotherapy and immunotherapy with the exception of alopecia, anorexia, bone pain, and tumor pain prior to entering this study.
Key exclusion criteria (13 listed)
- The presence of any of the following will exclude a subject from study enrollment.
- Patients with evidence of osteosarcoma outside of the lungs or pleura.
- Ongoing prior treatment toxicities > Grade 1 according to NCI CTCAE Version 5.0 with the exception of alopecia, anorexia, bone pain and tumor pain.
- Subjects receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Natalizumab.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NatalizumabAlso: TysabriNatalizumab is an FDA approved monotherapy for treatment of relapsing forms of MS. It is also indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active CD who have had an inadequate response to, or intolerance of, conventional therapies and TNF-α inhibitors. Traditional 3+3 escalation of Natalizumab at a weight-based dosing 2mg/kg not to exceed 300mg. If no subjects experience a dose limiting toxicity (DLT), 3 more subjects are enrolled at the next dose of 3mg/kg, not to exceed 300mg. If no subjects experience a DLT, 3 more subjects will be enrolled at the next and final dose of 4mg/kg, not to exceed 300mg. Phase II will continue if the subject has Complete Response (CR), Partial Response (PR) or Stable Disease (SD) of pOS, defined by RECIST 1.1 criteria after every 3 cycles after the first 6 cycles but not beyond 24 cycles. If subject has progressive disease after cycle 6, they will be removed from the study. | Drug | Phase I: Natalizumab |
Primary outcome
Dosing limiting toxicity
Time frame: 30 days after end of treatment (1 year)
Hematologic dose limiting toxicities: Grade 4 neutropenia or thrombocytopenia of > 7 days duration; or myelosuppression that causes a delay of > 8 weeks between treatment courses Non-hematologic dose-limiting toxicities: Any Grade 4 non-hematologic toxicity attributable to Natalizumab with the specific exclusion of: * Grade 4 nausea and vomiting responding to anti-emetics, alopecia, fatigue and drug related fever * Grade 4 fever * Any Grade 3 or greater neurologic toxicity * Any Grade 3 or greater anaphylaxis * Any Grade 2 or greater elevation in transaminases and bilirubin levels * Any Grade 4 non-hematologic toxicities (excluding alopecia, nausea and vomiting) that do not resolve to ≤ Grade 1 by 8 weeks following the most recent dose of Natalizumab
2 secondary outcomes
Clinical benefit rate
Time frame: 1 year after start of treatment
Overall survival measured in months
Time frame: Up to 3 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2025.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristen VanHeyst, DO principal investigator
University Hospitals Cleveland Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Natalizumab in people with Pulmonary Metastatic Osteosarcoma (pOS), run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dosing limiting toxicity (time frame: 30 days after end of treatment (1 year)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2025; AzTrials last refreshed its copy on 6 Nov 2026.