Pulmonary Metastatic Osteosarcoma (pOS) Clinical Trial
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.
| Status | Recruiting |
| Enrollment | 20 |
| Est. completion date | October 1, 2025 |
| Est. primary completion date | December 1, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 5 Years to 30 Years |
| Eligibility | Inclusion Criteria: - Subjects must have histologic verification of pOS. - 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 recovered from the acute toxic effects with = Grade 1 as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CASE 1718 Page 20 Version date: 9/11/18 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. Exclusion Criteria: The presence of any of the following will exclude a subject from study enrollment. - 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. - 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 can be completely surgically resected. |
| Country | Name | City | State |
|---|---|---|---|
| United States | University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center | Cleveland | Ohio |
| Lead Sponsor | Collaborator |
|---|---|
| Case Comprehensive Cancer Center |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 |
30 days after end of treatment (1 year) | |
| Secondary | 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 | 1 year after start of treatment | |
| Secondary | 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 | Up to 3 years |