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Study of RNA-lipid Particle (RNA-LP) Vaccines for Recurrent Pulmonary Osteosarcoma (OSA)

Primary Purpose

Pulmonary Osteosarcoma

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
RNA-LP vaccine
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Osteosarcoma focused on measuring pulmonary osteosarcoma, RNA-LP, vaccines, immunotherapy

Eligibility Criteria

0 Years - 39 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age < 39 years. Histopathologically proven recurrent pulmonary osteosarcoma. Must be eligible for thoracotomy (Arms 1 and 2 only). Patient must have been enrolled on a screening consent and have had sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs). Patients must have recovered from the effects of surgery, biopsy, postoperative infection, and other complications. Karnofsky Performance Status (KPS) or Lansky Performance Status (LPS) ≥ 60. Bone Marrow: ANC (Absolute neutrophil count) ≥ 1,000µl (absent treatment) Platelets ≥ 100,000/µl (absent treatment for at least 3 days) Hemoglobin > 8 g/dL Renal: BUN ≤ 25 mg/dl Creatinine ≤ 1.7 mg/dl Hepatic Bilirubin ≤ 2.0 mg/dl ALT ≤ 5 times institutional upper limits of normal for age AST ≤ 5 times institutional upper limits of normal for age Signed informed consent. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the legally authorized representative per institutional policy. For subjects of childbearing potential (SOCBP), negative urine or serum pregnancy test at enrollment. SOCBP must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug. Subjects with partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug. Exclusion Criteria: HIV, Hepatitis B, CMV, or Hepatitis C seropositive. Known active infection or immunosuppressive disease. Known severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization. Unstable cardiac arrhythmias, abnormalities, or transmural myocardial infarction within the last 6 months. Acute bacterial or fungal infection requiring intravenous antibiotics Chronic Obstructive Pulmonary Disease exacerbation or other known respiratory illness requiring hospitalization or precluding study therapy Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects. Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Patients with autoimmune disease requiring medical management with immunosuppressants. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy. Known active connective tissue disorders such as lupus or scleroderma that, in the investigator's opinion, place the patient at high risk for radiation toxicity. Pregnancy or subjects of childbearing potential and their partners who are sexually active and who are unwilling or unable to use an acceptable method of contraception for the entire study period; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Subjects must not be pregnant or breast-feeding. Subjects who require systemic corticosteroids above physiologic doses or not weaned to physiologic dosing within 1 week of scheduled vaccination. Subjects who are receiving any other investigational agents or who have been treated on any other therapeutic clinical protocols within 30 days prior to study entry. Subjects who are unwilling or unable to receive treatment and undergo follow-up evaluations at the enrolled Sunshine Consortium treatment site.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    RNA-LP vaccine

    Arm Description

    Outcomes

    Primary Outcome Measures

    Maximum tolerated dose
    Determine the maximum tolerated dose of RNA-LP vaccine.
    12 month event-free survival
    Determine if RN-LP vaccine therapy extends 12 month event-free survival. Event-free survival is defined as the time from start of treatment to either disease progression or death, whichever occurs first.

    Secondary Outcome Measures

    Event-free survival
    Determine the event-free survival in patients with recurrent pulmonary oseteosarcoma receiving RNA-LP vaccine. Event-free survival is defined as the time from start of treatment to either disease progression or death, whichever occurs first.
    Overall survival
    Determine the overall survival in patients with recurrent pulmonary oseteosarcoma receiving RNA-LP vaccine.

    Full Information

    First Posted
    December 13, 2022
    Last Updated
    January 25, 2023
    Sponsor
    University of Florida
    Collaborators
    The V Foundation for Cancer Research
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05660408
    Brief Title
    Study of RNA-lipid Particle (RNA-LP) Vaccines for Recurrent Pulmonary Osteosarcoma (OSA)
    Official Title
    Study of RNA-lipid Particle (RNA-LP) Vaccines for Recurrent Pulmonary Osteosarcoma (OSA)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2023 (Anticipated)
    Primary Completion Date
    October 2026 (Anticipated)
    Study Completion Date
    October 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Florida
    Collaborators
    The V Foundation for Cancer Research

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The investigators have shown that intravenous administration of tumor mRNA loaded lipid particles (LPs) localizes primarily to lung, transfect antigen presenting cells (APCs) and lead to an activated T cell response for induction of anti-tumor immunity. In contrast to other formulations, RNA-LPs recruit multiple arms of the immune system (i.e. innate/adaptive), and remodel the systemic/intratumoral immune milieu, which remain potent barriers for vaccine, cellular, and checkpoint inhibiting immunotherapies. After only a single RNA-LP vaccine, the bulk of systemic and intratumoral dendritic cells (DCs) in mice display an activated phenotype; these activated DCs (harvested from tumors) expand antigen specific T cell immunity. In immunologically resistant pulmonary osteosacroma murine tumor models (i.e. K7M2), RNA-LPs induce robust anti-tumor efficacy in settings where immune checkpoint inhibitors (i.e. anti-PD-L1 therapy) do not confer therapeutic benefit. We have already demonstrated safety of RNA-LPs in acute/chronic murine toxicity studies, and in client-owned canine trial. In this study, we will investigate the safety and immunologic activity of RNA-LP vaccine in patients with recurrent pulmonary osteosarcoma.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pulmonary Osteosarcoma
    Keywords
    pulmonary osteosarcoma, RNA-LP, vaccines, immunotherapy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    43 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    RNA-LP vaccine
    Arm Type
    Experimental
    Intervention Type
    Biological
    Intervention Name(s)
    RNA-LP vaccine
    Intervention Description
    All subjects will receive two doses of RNA-LP vaccine every two weeks and then once monthly for 12 months afterward. Subjects on the phase 1 portion of the study will be assigned to receive either 0.01 mg/kg mRNA encapsulated in 0.15 mg/kg LPs (dose level -1), 0.02 mg/kg mRNA encapsulated in 0.3 mg/kg LPs (dose level 0), 0.04 mg mRNA encapsulated in 0.6 mg/kg LPs (dose level +1), 0.08 mg mRNA encapsulated in 1.2 mg/kg LPs (dose level +2) following a 3 + 3 design. All subjects on the Phase II portion will receive the maximum tolerated dose determined in the phase I portion of the study.
    Primary Outcome Measure Information:
    Title
    Maximum tolerated dose
    Description
    Determine the maximum tolerated dose of RNA-LP vaccine.
    Time Frame
    14 months
    Title
    12 month event-free survival
    Description
    Determine if RN-LP vaccine therapy extends 12 month event-free survival. Event-free survival is defined as the time from start of treatment to either disease progression or death, whichever occurs first.
    Time Frame
    12 months
    Secondary Outcome Measure Information:
    Title
    Event-free survival
    Description
    Determine the event-free survival in patients with recurrent pulmonary oseteosarcoma receiving RNA-LP vaccine. Event-free survival is defined as the time from start of treatment to either disease progression or death, whichever occurs first.
    Time Frame
    3 years
    Title
    Overall survival
    Description
    Determine the overall survival in patients with recurrent pulmonary oseteosarcoma receiving RNA-LP vaccine.
    Time Frame
    3 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    0 Years
    Maximum Age & Unit of Time
    39 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age < 39 years. Histopathologically proven recurrent pulmonary osteosarcoma. Must be eligible for thoracotomy (Arms 1 and 2 only). Patient must have been enrolled on a screening consent and have had sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs). Patients must have recovered from the effects of surgery, biopsy, postoperative infection, and other complications. Karnofsky Performance Status (KPS) or Lansky Performance Status (LPS) ≥ 60. Bone Marrow: ANC (Absolute neutrophil count) ≥ 1,000µl (absent treatment) Platelets ≥ 100,000/µl (absent treatment for at least 3 days) Hemoglobin > 8 g/dL Renal: BUN ≤ 25 mg/dl Creatinine ≤ 1.7 mg/dl Hepatic Bilirubin ≤ 2.0 mg/dl ALT ≤ 5 times institutional upper limits of normal for age AST ≤ 5 times institutional upper limits of normal for age Signed informed consent. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the legally authorized representative per institutional policy. For subjects of childbearing potential (SOCBP), negative urine or serum pregnancy test at enrollment. SOCBP must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug. Subjects with partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug. Exclusion Criteria: HIV, Hepatitis B, CMV, or Hepatitis C seropositive. Known active infection or immunosuppressive disease. Known severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization. Unstable cardiac arrhythmias, abnormalities, or transmural myocardial infarction within the last 6 months. Acute bacterial or fungal infection requiring intravenous antibiotics Chronic Obstructive Pulmonary Disease exacerbation or other known respiratory illness requiring hospitalization or precluding study therapy Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects. Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Patients with autoimmune disease requiring medical management with immunosuppressants. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy. Known active connective tissue disorders such as lupus or scleroderma that, in the investigator's opinion, place the patient at high risk for radiation toxicity. Pregnancy or subjects of childbearing potential and their partners who are sexually active and who are unwilling or unable to use an acceptable method of contraception for the entire study period; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Subjects must not be pregnant or breast-feeding. Subjects who require systemic corticosteroids above physiologic doses or not weaned to physiologic dosing within 1 week of scheduled vaccination. Subjects who are receiving any other investigational agents or who have been treated on any other therapeutic clinical protocols within 30 days prior to study entry. Subjects who are unwilling or unable to receive treatment and undergo follow-up evaluations at the enrolled Sunshine Consortium treatment site.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Shannon Alford, MPH
    Phone
    (352) 273-8146
    Email
    PMO@cancer.ufl.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    John Ligon, MD
    Organizational Affiliation
    University of Florida
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Study of RNA-lipid Particle (RNA-LP) Vaccines for Recurrent Pulmonary Osteosarcoma (OSA)

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