Un estudio de escalada de dosis de AV-380 en pacientes con cáncer metastásico con caquexia
Un estudio de fase 1 de escalada de dosis de AV-380 en combinación con quimioterapia de atención estándar en pacientes con cáncer metastásico con caquexia y niveles elevados de 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.
Descripción general del estudio
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
California
-
Beverly Hills, California, Estados Unidos, 90211
- Beverly Hills Cancer Center
-
Lakewood, California, Estados Unidos, 90712
- Cancer and Blood Specialty Clinic
-
Newport Beach, California, Estados Unidos, 92663
- Hoag Memorial Hospital
-
-
Connecticut
-
Hartford, Connecticut, Estados Unidos, 06102
- Hartford Hospital
-
-
Florida
-
Orlando, Florida, Estados Unidos, 32804
- Advent Health Orlando Hospital
-
-
Nebraska
-
Omaha, Nebraska, Estados Unidos, 68130
- Nebraska Cancer Specialists
-
-
New Jersey
-
East Brunswick, New Jersey, Estados Unidos, 08816
- Astera Cancer Care
-
-
New York
-
Shirley, New York, Estados Unidos, 11967
- New York Cancer And Blood Specialists
-
-
Oregon
-
Portland, Oregon, Estados Unidos, 97239
- Oregon Health and Science University
-
-
South Carolina
-
Charleston, South Carolina, Estados Unidos, 29425
- MUSC Hollings Cancer Center
-
-
Tennessee
-
Nashville, Tennessee, Estados Unidos, 37232
- Vanderbilt University Henry-Joyce Cancer Clinic
-
-
Texas
-
Kingwood, Texas, Estados Unidos, 77339
- Community Clinical Trials
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
-
Patient must be ≥ 18 years of age at the time of signing the informed consent.
-
Patients with histologically confirmed solid tumor cancer who are actively receiving SoC therapy for this cancer.
-
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%
-
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: 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. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Assessment of adverse events (AEs)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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.
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Cmax
Periodo de tiempo: 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
Periodo de tiempo: 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
|
|
AUC(0-t)
Periodo de tiempo: 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.
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Nivel sérico de GDF-15
Periodo de tiempo: Desde la inscripción hasta la última visita de seguimiento aproximadamente 60 días después de la dosis.
|
Desde la inscripción hasta la última visita de seguimiento aproximadamente 60 días después de la dosis.
|
|
|
Immunogenicity
Periodo de tiempo: From first dose to the last follow-up visit approximately 60-days post dose.
|
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.
|
|
Weight
Periodo de tiempo: From enrollment to the last follow-up visit approximately 60-days post dose.
|
Change from baseline body weight during the study |
From enrollment to the last follow-up visit approximately 60-days post dose.
|
|
Patient-Reported Outcomes
Periodo de tiempo: 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)
Periodo de tiempo: 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
|
|
Physical Function
Periodo de tiempo: 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
|
|
Albumin and CRP
Periodo de tiempo: From enrollment to the last follow-up visit approximately 60-days post dose.
|
Change from baseline in albumin and CRP levels |
From enrollment to the last follow-up visit approximately 60-days post dose.
|
|
Tumor status
Periodo de tiempo: From enrollment to the last follow-up visit approximately 60-days post dose.
|
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.
|
|
Biomarkers
Periodo de tiempo: From first dose to the last follow-up visit approximately 60-days post dose.
|
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.
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- AV-380-22-102
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .