Studie eskalace dávky AV-380 u pacientů s metastatickým karcinomem s kachexií
Fáze 1 studie eskalace dávky AV-380 v kombinaci s chemoterapií standardní péče u pacientů s metastatickým karcinomem s kachexií a zvýšenými hladinami GDF-15
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.
Přehled studie
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
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California
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Beverly Hills, California, Spojené státy, 90211
- Beverly Hills Cancer Center
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Lakewood, California, Spojené státy, 90712
- Cancer and Blood Specialty Clinic
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Newport Beach, California, Spojené státy, 92663
- Hoag Memorial Hospital
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Connecticut
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Hartford, Connecticut, Spojené státy, 06102
- Hartford Hospital
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Florida
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Orlando, Florida, Spojené státy, 32804
- Advent Health Orlando Hospital
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Nebraska
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Omaha, Nebraska, Spojené státy, 68130
- Nebraska Cancer Specialists
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New Jersey
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East Brunswick, New Jersey, Spojené státy, 08816
- Astera Cancer Care
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New York
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Shirley, New York, Spojené státy, 11967
- New York Cancer And Blood Specialists
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Oregon
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Portland, Oregon, Spojené státy, 97239
- Oregon Health and Science University
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South Carolina
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Charleston, South Carolina, Spojené státy, 29425
- MUSC Hollings Cancer Center
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Tennessee
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Nashville, Tennessee, Spojené státy, 37232
- Vanderbilt University Henry-Joyce Cancer Clinic
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Texas
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Kingwood, Texas, Spojené státy, 77339
- Community Clinical Trials
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 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. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Assessment of adverse events (AEs)
Časové okno: From enrollment to the last follow-up visit approximately 60-days post dose
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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
Časové okno: 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)
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Laboratory Abnormalities
Časové okno: From enrollment to the last follow-up visit approximately 60-days post dose.
|
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.
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Cmax
Časové okno: 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.
|
|
Tmax
Časové okno: 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)
Časové okno: From first dose to the last follow-up visit approximately 60-days post dose.
|
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.
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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Hladina séra GDF-15
Časové okno: Od zápisu do poslední následné návštěvy přibližně 60 dnů po dávce.
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Od zápisu do poslední následné návštěvy přibližně 60 dnů po dávce.
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Immunogenicity
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
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Lumbar (L3) Skeletal Muscle Index (L3SMI)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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.
|
Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- AV-380-22-102
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