Een dosisescalatiestudie van AV-380 bij patiënten met gemetastaseerde kanker met cachexie
Een fase 1-dosisescalatiestudie van AV-380 in combinatie met standaardchemotherapie bij patiënten met gemetastaseerde kanker met cachexie en verhoogde GDF-15-spiegels
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.
Studie Overzicht
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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California
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Beverly Hills, California, Verenigde Staten, 90211
- Beverly Hills Cancer Center
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Lakewood, California, Verenigde Staten, 90712
- Cancer and Blood Specialty Clinic
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Newport Beach, California, Verenigde Staten, 92663
- Hoag Memorial Hospital
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Connecticut
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Hartford, Connecticut, Verenigde Staten, 06102
- Hartford Hospital
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Florida
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Orlando, Florida, Verenigde Staten, 32804
- Advent Health Orlando Hospital
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Nebraska
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Omaha, Nebraska, Verenigde Staten, 68130
- Nebraska Cancer Specialists
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New Jersey
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East Brunswick, New Jersey, Verenigde Staten, 08816
- Astera Cancer Care
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New York
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Shirley, New York, Verenigde Staten, 11967
- New York Cancer And Blood Specialists
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Oregon
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Portland, Oregon, Verenigde Staten, 97239
- Oregon Health and Science University
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South Carolina
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Charleston, South Carolina, Verenigde Staten, 29425
- MUSC Hollings Cancer Center
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Tennessee
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Nashville, Tennessee, Verenigde Staten, 37232
- Vanderbilt University Henry-Joyce Cancer Clinic
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Texas
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Kingwood, Texas, Verenigde Staten, 77339
- Community Clinical Trials
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Sequentiële toewijzing
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 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. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Assessment of adverse events (AEs)
Tijdsspanne: 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
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Toxicity
Tijdsspanne: While receiving study drug (up to 4 months)
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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
Tijdsspanne: 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.
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Cmax
Tijdsspanne: From first dose to the last follow-up visit approximately 60-days post dose.
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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
Tijdsspanne: From first dose to the last follow-up visit approximately 60-days post dose
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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)
Tijdsspanne: 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.
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Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Serumniveau van GDF-15
Tijdsspanne: Van inschrijving tot het laatste vervolgbezoek bezoek ongeveer 60 dagen na de dosis.
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Van inschrijving tot het laatste vervolgbezoek bezoek ongeveer 60 dagen na de dosis.
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Immunogenicity
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: From enrollment to the end of treatment, approximately 4 months
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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)
Tijdsspanne: From enrollment to the end of treatment, approximately 4 months
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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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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.
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Medewerkers en onderzoekers
Sponsor
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- AV-380-22-102
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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