Relacorilant con Nab-Paclitaxel y Gemcitabina en Pacientes con Adenocarcinoma Pancreático Metastásico
Un ensayo de fase 2, de un solo brazo, de relacorilant en combinación con nab-paclitaxel y gemcitabina en pacientes con adenocarcinoma pancreático metastásico previamente no tratado
This is a 2-part, Phase 2 study to evaluate the safety, tolerability, dosing, pharmacokinetics (PK), and efficacy of relacorilant in combination with nab-paclitaxel and gemcitabine in chemotherapy-naïve patients with metastatic pancreatic adenocarcinoma (PDAC).
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This study will include 2 parts. In Part 1 (dose finding), approximately 6 patients will be enrolled to individual dose-finding cohorts. Cohorts will receive various dose concentrations of relacorilant, nab-paclitaxel, and gemcitabine at various dosing schedules. In all dose-finding cohorts, relacorilant will be administered orally under fed conditions, once daily for 3 days on the day before (excluding Cycle 1 Day -1), the day of, and the day after nab-paclitaxel and gemcitabine. Enrollment will be paused after each cohort has been filled until the safety review committee (SRC) provides recommendations. If maximum tolerated dose (MTD) criteria are not met in a cohort, then either a dose-finding cohort at a more intense dose and/or schedule may be enrolled, or a dose and schedule at/below the MTD may be selected as the optimal dose and schedule, and Part 2 may be initiated. If MTD criteria are met, then a dose-finding cohort at a less intense dose and/or schedule may be enrolled, or dose-finding may end without proceeding to Part 2.
In Part 2 (expansion), each patient will receive the optimal dose and schedule of relacorilant, nab-paclitaxel, and gemcitabine as identified in Part 1. Analysis of Part 2 will include data for patients from Part 1 who were enrolled in the optimal dose and schedule used in Part 2.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Corcept Therapeutics
- Número de teléfono: (714) 721-1505
- Correo electrónico: corceptstudy558@corcept.com
Ubicaciones de estudio
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Arizona
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Scottsdale, Arizona, Estados Unidos, 85258
- Reclutamiento
- Site 02
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California
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Los Angeles, California, Estados Unidos, 90025
- Reclutamiento
- Site 04
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Orange, California, Estados Unidos, 92868
- Reclutamiento
- Site 12
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Florida
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Jacksonville, Florida, Estados Unidos, 32224
- Reclutamiento
- Site 17
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Reclutamiento
- Site 06
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Indiana
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Goshen, Indiana, Estados Unidos, 46526
- Reclutamiento
- Site 14
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Kansas
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Westwood, Kansas, Estados Unidos, 66205
- Reclutamiento
- Site 15
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Michigan
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Grand Rapids, Michigan, Estados Unidos, 49503
- Reclutamiento
- Site 03
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Reclutamiento
- Site 18
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New Jersey
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East Brunswick, New Jersey, Estados Unidos, 08816
- Reclutamiento
- Site 10
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Morristown, New Jersey, Estados Unidos, 07960
- Reclutamiento
- Site 11
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New York
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Albany, New York, Estados Unidos, 12206
- Reclutamiento
- Site 08
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Lake Success, New York, Estados Unidos, 11042
- Retirado
- Site 05
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Shirley, New York, Estados Unidos, 11967
- Reclutamiento
- Site 07
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45219
- Reclutamiento
- Site 13
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Toledo, Ohio, Estados Unidos, 43614
- Reclutamiento
- Site 20
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Reclutamiento
- Site 09
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Nashville, Tennessee, Estados Unidos, 37232
- Reclutamiento
- Site 19
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Texas
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Fort Worth, Texas, Estados Unidos, 76104
- Reclutamiento
- Site 16
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San Antonio, Texas, Estados Unidos, 78229
- Reclutamiento
- Site 01
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Signed and dated informed consent form prior to screening procedures
- Histologic diagnosis or cytologic diagnosis of pancreatic adenocarcinoma (PDAC)
- Initial diagnosis of metastatic disease occurred ≤9 weeks prior to enrollment in the study
- Life expectancy of ≥3 months
- Radiographic confirmation of metastatic disease with at least 1 distant tumor metastasis measurable on radiology imaging per RECIST version 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Able to provide informed consent and comply with protocol requirements
- Able to swallow and retain oral medication and does not have uncontrolled emesis
- Has adequate gastrointestinal absorption
- Received no prior systemic anticancer chemotherapy to treat metastatic PDAC. Treatment of PDAC with a single agent RAS inhibitor is permitted.
- If a patient received prior treatment of PDAC with chemotherapy, disease progression must have occurred >12 months after completing the last dose, and no persistent treatment-related toxicities can be present.
- Adequate organ function
- Negative pregnancy test for patients of childbearing potential
- Agree to use protocol defined precautions to avoid pregnancy
Exclusion Criteria:
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Any major surgery within 4 weeks prior to enrollment
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Prior treatment as follows:
- Radiotherapy, surgery, chemotherapy, immunotherapy, investigational therapy for the treatment of metastatic disease
- Systemic, inhaled, or prescription strength topical corticosteroids within 5 times the half-life of the corticosteroid used prior to first dose of study drug
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Received gemcitabine or nab-paclitaxel to treat their PDAC
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Known germline or somatic breast cancer gene (BRCA) mutation
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Peripheral neuropathy from any cause >Grade 1
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Medical conditions requiring chronic or frequent treatment with corticosteroids
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History of severe hypersensitivity or severe reaction to any of study drugs or their excipients
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Concurrent treatment with mifepristone or other glucocorticoid receptor modulators.
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Uncontrolled condition(s) which, may confound the results of the trial or interfere with the patient's safety or participation
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Active infection with HIV, hepatitis C or hepatitis B virus
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Known untreated parenchymal brain metastasis or uncontrolled central nervous system metastases
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History of other malignancy within 3 years prior to enrollment
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Taking protocol-prohibited medications
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Concurrent treatment with other investigational treatment studies for cancer
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Has received a live vaccine within 30 days prior to the study start date
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 |
|---|---|
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Experimental: Relacorilant in Combination with Nab-paclitaxel and Gemcitabine
The patient will receive relacorilant administered orally under fed conditions, once daily for 3 consecutive days on the day before (excluding Cycle 1 Day -1), the day of, and the day after nab-paclitaxel and gemcitabine intravenous (IV) infusions. Various dose levels and dosing schedules of relacorilant, nab-paclitaxel, and gemcitabine will be evaluated. On days when relacorilant, nab-paclitaxel, and gemcitabine are administered, relacorilant will be administered first, then nab-paclitaxel, and gemcitabine last. |
Relacorilant will be administered as capsules for oral dosing.
Otros nombres:
Nab-paclitaxel will be administered via IV infusion. Gemcitabine will be administered via IV infusion. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of Patients with 1 or More Adverse Events (AEs) Leading to Study Drug Discontinuations or Dose Modifications (Part 1)
Periodo de tiempo: Time of first dose up to 30 days after last dose
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Time of first dose up to 30 days after last dose
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Percent of Patients who Experience Dose Limiting Toxicity (DLT) (Part 1)
Periodo de tiempo: Up to 28 days after the first dose of study treatment
|
The percentage of patients with a DLT is used to estimate maximum tolerated dose (MTD), the most intense dose/schedule among those evaluated at which <33% of patients experience DLT. |
Up to 28 days after the first dose of study treatment
|
|
Progression-Free Survival (PFS) (Part 2)
Periodo de tiempo: From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
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To evaluate PFS as the time from enrollment until first documented progressive disease (PD) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as determined by the Investigator, or death due to any cause, whichever comes first. |
From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Maximum Plasma Concentration (Cmax) of Relacorilant (Part 1 and Part 2)
Periodo de tiempo: Pre- and postdose on Cycle 1 Day 15 (each cycle is 28 days)
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Pre- and postdose on Cycle 1 Day 15 (each cycle is 28 days)
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Area Under the Plasma Concentration-time Curve (AUC) of Relacorilant (Part 1 and Part 2)
Periodo de tiempo: Pre- and postdose on Cycle 1 Day 15 (each cycle is 28 days)
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Pre- and postdose on Cycle 1 Day 15 (each cycle is 28 days)
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Cmax of Nab-paclitaxel (Part 1 and Part 2)
Periodo de tiempo: At serial timepoints postdose on Cycle 1 Day 15 (each cycle is 28 days)
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At serial timepoints postdose on Cycle 1 Day 15 (each cycle is 28 days)
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AUC of Nab-paclitaxel (Part 1 and Part 2)
Periodo de tiempo: At serial timepoints postdose on Cycle 1 Day 15 (each cycle is 28 days)
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At serial timepoints postdose on Cycle 1 Day 15 (each cycle is 28 days)
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Overall Survival (OS) (Part 2)
Periodo de tiempo: From date of enrollment until the date of death from any cause, whichever comes first, assessed up to 19 months
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From date of enrollment until the date of death from any cause, whichever comes first, assessed up to 19 months
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Best Overall Response (BOR) (Part 2)
Periodo de tiempo: From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
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From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
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Number of Patients with 1 or More Adverse Events (Part 2)
Periodo de tiempo: Time of first dose up to 30 days after last dose
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Time of first dose up to 30 days after last dose
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Number of Patients with Treatment-related Adverse Events (Part 2)
Periodo de tiempo: Time of first dose up to 30 days after last dose
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Time of first dose up to 30 days after last dose
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Number of Patients with Adverse Events by Severity (Part 2)
Periodo de tiempo: Time of first dose up to 30 days after last dose
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Time of first dose up to 30 days after last dose
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Number of Patients With 1 or More Adverse Events Leading to Study Drug Discontinuation (Part 2)
Periodo de tiempo: Time of first dose up to 30 days after last dose
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Time of first dose up to 30 days after last dose
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Objective Response Rate (ORR) (Part 2)
Periodo de tiempo: From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
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To evaluate the proportion of patients with measurable disease at Baseline who attain complete response (CR) or partial response (PR) by RECIST version 1.1. |
From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
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Duration of Response (DoR) (Part 2)
Periodo de tiempo: From date of first objective response until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
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To evaluate DOR as the time from the first CR or PR to first documented PD or death, whichever comes first. |
From date of first objective response until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months
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Clinical Benefit Rate (CBR) (Part 2)
Periodo de tiempo: Week 24
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To evaluate clinical benefit rate as the proportion of patients who attain CR, PR, or stable disease (SD) at Week 24 as per RECIST version 1.1. |
Week 24
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Cancer Antigen 19-9 (CA19-9) Kinetics (Part 2)
Periodo de tiempo: Baseline to Weeks 4, 8, and 16
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To evaluate change in CA19-9 from baseline in patients who had an elevated baseline CA19-9 and change in CA19-9 at Weeks 4, 8, and 16 from baseline in all patients. |
Baseline to Weeks 4, 8, and 16
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Director de estudio: Danny Nguyen, Corcept Therapeutics
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
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
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades del sistema endocrino
- Neoplasias por sitio
- Neoplasias
- Neoplasias por tipo histológico
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Neoplasias de glándulas endocrinas
- Enfermedades pancreáticas
- Neoplasias Glandulares y Epiteliales
- Carcinoma
- Neoplasias ductales, lobulillares y medulares
- Neoplasias pancreáticas
- Carcinoma Ductal
- Adenocarcinoma
- Carcinoma Ductal Pancreático
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Desoxicitidina
- Citidina
- Nucleósidos de pirimidina
- Pirimidinas
- Gemcitabina
- Paclitaxel de 130 nm en albúmina
- relacorilante
Otros números de identificación del estudio
- CORT125134-558
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.
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