Natalizumab in Recurrent, Refractory or Progressive Pulmonary Metastatic Osteosarcoma

NCT03811886 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: CASE1718
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pulmonary Metastatic Osteosarcoma (pOS)

Keywords

Natalizumab

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Clinical benefit rate

  1 year after start of treatment

• Overall survival measured in months

  Up to 3 years

Study Arms (1)

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.

Drug: Natalizumab

Interventions

Natalizumab DRUG

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.

Also known as: Tysabri

Phase I: Natalizumab

Eligibility Criteria

• Age: 5 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Interventions

Natalizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kristen VanHeyst, DO

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: January 22, 2019
• Study Start: December 1, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): October 1, 2026
• Last Updated: January 15, 2025

Record last verified: 2025-01

Locations

US (1)