En doseeskaleringsstudie av AV-380 hos metastaserende kreftpasienter med kakeksi
En fase 1-doseeskaleringsstudie av AV-380 i kombinasjon med standardbehandling av kjemoterapi hos metastaserende kreftpasienter med kakeksi og forhøyede GDF-15-nivåer
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.
Studieoversikt
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
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California
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Beverly Hills, California, Forente stater, 90211
- Beverly Hills Cancer Center
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Lakewood, California, Forente stater, 90712
- Cancer and Blood Specialty Clinic
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Newport Beach, California, Forente stater, 92663
- Hoag Memorial Hospital
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Connecticut
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Hartford, Connecticut, Forente stater, 06102
- Hartford Hospital
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Florida
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Orlando, Florida, Forente stater, 32804
- Advent Health Orlando Hospital
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Nebraska
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Omaha, Nebraska, Forente stater, 68130
- Nebraska Cancer Specialists
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New Jersey
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East Brunswick, New Jersey, Forente stater, 08816
- Astera Cancer Care
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New York
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Shirley, New York, Forente stater, 11967
- New York Cancer And Blood Specialists
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Oregon
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Portland, Oregon, Forente stater, 97239
- Oregon Health and Science University
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South Carolina
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Charleston, South Carolina, Forente stater, 29425
- MUSC Hollings Cancer Center
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Tennessee
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Nashville, Tennessee, Forente stater, 37232
- Vanderbilt University Henry-Joyce Cancer Clinic
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Texas
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Kingwood, Texas, Forente stater, 77339
- Community Clinical Trials
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
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 studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Sekvensiell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
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)
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|
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 |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Cmax
Tidsramme: 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
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 |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Serumnivå av GDF-15
Tidsramme: Fra påmelding til siste oppfølgingsbesøk omtrent 60 dager etter dose.
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Fra påmelding til siste oppfølgingsbesøk omtrent 60 dager etter dose.
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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
|
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Lumbar (L3) Skeletal Muscle Index (L3SMI)
Tidsramme: 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
Tidsramme: From enrollment to the end of treatment, approximately 4 months
|
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.
|
Samarbeidspartnere og etterforskere
Sponsor
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- AV-380-22-102
Plan for individuelle deltakerdata (IPD)
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