En dosiseskaleringsundersøgelse af AV-380 i metastatiske kræftpatienter med kakeksi
Et fase 1-dosiseskaleringsstudie af AV-380 i kombination med standardbehandling kemoterapi hos metastaserende kræftpatienter med kakeksi og forhøjede GDF-15-niveauer
This open label ascending dose study is designed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AV-380 in cancer patients with Cachexia. AV-380 is an immunoglobulin (Ig) G1 monoclonal antibody (mAb) intended to bind circulating human growth differentiation factor 15 (GDF-15), a cytokine involved in cancer-induced cachexia.
Studieoversigt
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
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California
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Beverly Hills, California, Forenede Stater, 90211
- Beverly Hills Cancer Center
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Lakewood, California, Forenede Stater, 90712
- Cancer and Blood Specialty Clinic
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Newport Beach, California, Forenede Stater, 92663
- Hoag Memorial Hospital
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Connecticut
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Hartford, Connecticut, Forenede Stater, 06102
- Hartford Hospital
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Florida
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Orlando, Florida, Forenede Stater, 32804
- Advent Health Orlando Hospital
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Nebraska
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Omaha, Nebraska, Forenede Stater, 68130
- Nebraska Cancer Specialists
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New Jersey
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East Brunswick, New Jersey, Forenede Stater, 08816
- Astera Cancer Care
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New York
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Shirley, New York, Forenede Stater, 11967
- New York Cancer And Blood Specialists
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Oregon
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Portland, Oregon, Forenede Stater, 97239
- Oregon Health and Science University
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South Carolina
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Charleston, South Carolina, Forenede Stater, 29425
- MUSC Hollings Cancer Center
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37232
- Vanderbilt University Henry-Joyce Cancer Clinic
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Texas
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Kingwood, Texas, Forenede Stater, 77339
- Community Clinical Trials
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
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Patient must be ≥ 18 years of age at the time of signing the informed consent.
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Patients with histologically confirmed solid tumor cancer who are actively receiving SoC therapy for this cancer.
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Patients with cachexia as defined by Fearon criteria:
- Weight loss > 5% over past 6 months (in absence of simple starvation), or
- BMI < 20 kg/m2 and any degree of weight loss > 2%, or
- Sarcopenia and any degree of weight loss > 2%
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Patients with life expectancy ≥ 3 months
Exclusion Criteria:
- History of allergic or anaphylactic reaction to any monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibody
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 2 weeks before first dose of study treatment.
- Myocardial infarction or heart failure of New York Heart Association Grade 3-4 within 3 months prior to start of protocol therapy
- Uncontrolled pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- Cachexia is caused by other reasons (e.g., severe chronic obstructive pulmonary disease, heart failure, or HIV/AIDS), or the patient has uncontrolled reversible causes of reduced oral food intake, including, but not limited to, oral mucositis, nausea/vomiting, diarrhea, and/or obstruction, impairing the patient's ability to eat as determined by the Investigator.
- Patients receiving tube feedings or parenteral nutrition at the time of Screening.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Dose Escalation Cohorts
Experimental: Dose escalation cohorts of AV-380 administered by IV infusion |
AV-380 is an immunoglobulin (Ig) G1 monoclonal antibody (mAb) intended to bind circulating human growth differentiation factor 15 (GDF-15), a cytokine involved in cancer-induced cachexia. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Assessment of adverse events (AEs)
Tidsramme: From enrollment to the last follow-up visit approximately 60-days post dose
|
AEs as characterized by incidence, type, frequency, and severity (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE]) |
From enrollment to the last follow-up visit approximately 60-days post dose
|
|
Toxicity
Tidsramme: While receiving study drug (up to 4 months)
|
Dose-limiting Toxicity (DLT) events observed at increasing doses of AV-380 |
While receiving study drug (up to 4 months)
|
|
Laboratory Abnormalities
Tidsramme: From enrollment to the last follow-up visit approximately 60-days post dose.
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Laboratory abnormalities as characterized by type, frequency, severity (graded according to NCI-CTCAE v5.0) and timing. |
From enrollment to the last follow-up visit approximately 60-days post dose.
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Cmax
Tidsramme: From first dose to the last follow-up visit approximately 60-days post dose.
|
Maximum observed plasma concentration for AV-380 |
From first dose to the last follow-up visit approximately 60-days post dose.
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Tmax
Tidsramme: From first dose to the last follow-up visit approximately 60-days post dose
|
Time to reach the Cmax for AV-380 |
From first dose to the last follow-up visit approximately 60-days post dose
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AUC(0-t)
Tidsramme: From first dose to the last follow-up visit approximately 60-days post dose.
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Area under the plasma concentration-time curve from zero time to the last measurable point for AV-380 |
From first dose to the last follow-up visit approximately 60-days post dose.
|
Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Serumniveau af GDF-15
Tidsramme: Fra tilmelding til det sidste opfølgningsbesøg ca. 60 dage efter dosis.
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Fra tilmelding til det sidste opfølgningsbesøg ca. 60 dage efter dosis.
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Immunogenicity
Tidsramme: From first dose to the last follow-up visit approximately 60-days post dose.
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Serum levels of Anti-Drug Antibody (ADA) against AV-380 and their potential relationship with AEs and serum levels of GDF-15 |
From first dose to the last follow-up visit approximately 60-days post dose.
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Weight
Tidsramme: From enrollment to the last follow-up visit approximately 60-days post dose.
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Change from baseline body weight during the study |
From enrollment to the last follow-up visit approximately 60-days post dose.
|
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Patient-Reported Outcomes
Tidsramme: From enrollment to the end of treatment, approximately 4 months
|
Change from baseline in the following questionnaires: Functional Assessment of Anorexia Cachexia Therapy (FAACT); Patient global impression of severity (PGI-S) and patient global impression of change (PGI-C) for appetite, fatigue, and physical activity. |
From enrollment to the end of treatment, approximately 4 months
|
|
Lumbar (L3) Skeletal Muscle Index (L3SMI)
Tidsramme: From enrollment to the end of treatment, approximately 4 months
|
Measurement of a cross-sectional area of muscle at the level of the third lumbar vertebra (L3) using computed tomography (CT) scan |
From enrollment to the end of treatment, approximately 4 months
|
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Physical Function
Tidsramme: From enrollment to the end of treatment, approximately 4 months
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Change from baseline in physical function endpoints, including Short Physical Performance Battery test and digital measures of non-sedentary time |
From enrollment to the end of treatment, approximately 4 months
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Albumin and CRP
Tidsramme: From enrollment to the last follow-up visit approximately 60-days post dose.
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Change from baseline in albumin and CRP levels |
From enrollment to the last follow-up visit approximately 60-days post dose.
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Tumor status
Tidsramme: From enrollment to the last follow-up visit approximately 60-days post dose.
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Evaluate the effect of AV-380 on tumor burden and tumor status, per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) |
From enrollment to the last follow-up visit approximately 60-days post dose.
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Biomarkers
Tidsramme: From first dose to the last follow-up visit approximately 60-days post dose.
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including activin A and cytokine levels (e.g., monocyte chemoattractant protein-1 [MCP-1] and proinflammatory) |
From first dose to the last follow-up visit approximately 60-days post dose.
|
Samarbejdspartnere og efterforskere
Sponsor
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- AV-380-22-102
Plan for individuelle deltagerdata (IPD)
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