Cabazitaxel Versus the Switch to Alternative AR Targeted Therapy Enzalutamide or Abiraterone in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Primary Resistant Patients to Abiraterone or Enzalutamide (PRIMCAB)
19 de junio de 2019 actualizado por: Sanofi
Phase II, Randomized, Open-label, Multicenter Study in Chemotherapy-naïve Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Who Have PRIMary Resistance to Abiraterone Acetate or Enzalutamide Treatment Comparing the Anti-tumor Effect of CABazitaxel to Alternative Androgen Receptors (AR) Targeted Therapy
Primary Objective:
To demonstrate the superiority in term of radiographic Progression-Free Survival (rPFS) of cabazitaxel at at 25 milligram per meter square (mg/m^2) plus prednisone (Arm A) versus either enzalutamide at 160 milligram (mg) once daily or abiraterone acetate at 1000 mg once daily plus prednisone (Arm B) in chemotherapy-naïve participants with metastatic Castration-Resistant Prostate Cancer (mCRPC) who have disease progression while receiving androgen receptor (AR) targeted therapy (abiraterone plus prednisone or enzalutamide) within 12 months of treatment initiation (≤12 months).
Secondary Objective:
- To compare efficacy for:
- Prostate-specific antigen (PSA) response rate and Time to PSA progression (TTPP).
- Progression Free Survival (PFS).
- Overall Survival (OS).
- Tumor response rate in participants with measurable disease (RECIST 1.1)
- Pain response and time to pain progression.
- Symptomatic skeletal events (SSE) rate and time to occurrence of any SSE.
- To analyze messenger ribonucleic acids (mRNAs) including androgen-receptor splice variant 7 messenger RNA (AR-V7) as a biomarker in Circulating Tumor Cells (CTCs).
- To evaluate safety in the 2 treatment arms.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
The duration of the study per participant was approximately 2 years.
Each participant was treated until radiographic disease progression, unacceptable toxicity, or participants refusal of further study treatment, and each participant was followed after completion of study treatment until death, study cutoff date, or withdrawal of participant consent.
Tipo de estudio
Intervencionista
Inscripción (Actual)
8
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
-
Edmonton, Canadá, T6G 1Z2
- Investigational Site Number 124003
-
Greenfield Park, Canadá, J4V2H1
- Investigational Site Number 124010
-
Hamilton, Canadá, L8V 5C2
- Investigational Site Number 124005
-
London, Canadá, N6A 4L6
- Investigational Site Number 124004
-
Montreal, Canadá, H2L 4M1
- Investigational Site Number 124002
-
Montreal, Canadá, H2W1S6
- Investigational Site Number 124006
-
Ottawa, Canadá, K1H8L6
- Investigational Site Number 124007
-
Quebec, Canadá, G1R 2J6
- Investigational Site Number 124009
-
Saskatoon, Canadá, S7N4H4
- Investigational Site Number 124008
-
Vancouver, Canadá, N5Z4E6
- Investigational Site Number 124001
-
-
-
-
Alabama
-
Muscle Shoals, Alabama, Estados Unidos, 35661
- Investigational Site Number 840030
-
-
Alaska
-
Anchorage, Alaska, Estados Unidos, 99508
- Investigational Site Number 840024
-
-
California
-
Anaheim, California, Estados Unidos, 92801
- Investigational Site Number 840028
-
Sacramento, California, Estados Unidos, 95817
- Investigational Site Number 840004
-
-
Florida
-
Boca Raton, Florida, Estados Unidos, 33486
- Investigational Site Number 840002
-
Lakeland, Florida, Estados Unidos, 33805
- Investigational Site Number 840027
-
Port Saint Lucie, Florida, Estados Unidos, 34952
- Investigational Site Number 840006
-
-
Illinois
-
Ottawa, Illinois, Estados Unidos, 61350
- Investigational Site Number 840015
-
-
Louisiana
-
Covington, Louisiana, Estados Unidos, 70433
- Investigational Site Number 840001
-
Metairie, Louisiana, Estados Unidos, 70006
- Investigational Site Number 840017
-
-
Maryland
-
Rockville, Maryland, Estados Unidos, 20850
- Investigational Site Number 840012
-
-
Nebraska
-
Omaha, Nebraska, Estados Unidos, 68198
- Investigational Site Number 840026
-
-
Ohio
-
Canton, Ohio, Estados Unidos, 44718
- Investigational Site Number 840022
-
-
South Carolina
-
Myrtle Beach, South Carolina, Estados Unidos, 29572
- Investigational Site Number 840016
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Masculino
Descripción
Inclusion criteria:
- Diagnosis of histologically or cytologically confirmed prostate adenocarcinoma.
- Metastatic disease.
- Progressive disease (PD) while receiving AR targeted therapy with abiraterone acetate or enzalutamide within 12 months of treatment initiation (≤12 months) by at least one of the following:
- Progression in measurable disease Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Appearance of 2 or more new bone lesions according to Prostate Cancer Working Group 2 (PCWG2).
- Rising PSA defined (PCWG2) as at least two consecutive rises in PSA to be documented over a reference value (measure 1) taken at least one week apart.
- A PSA value of at least 2 nanogram/milliliter (ng/mL) is required at study entry.
- Effective castration (serum testosterone levels ≤0.5 ng/mL).
- Prior AR targeted therapy (abiraterone acetate or enzalutamide) must be stopped at least 2 weeks before study treatment.
- Signed written informed consent.
Exclusion criteria:
- Prior chemotherapy for prostate cancer, except estramustine and except adjuvant/neoadjuvant treatment completed >3 years ago. No further anti-cancer therapy after the previous AR targeted therapy and before inclusion. Prior docetaxel in hormone sensitive setting is allowed if completed >1 year before randomization. Prior immunotherapy is allowed.
- Less than 28 days elapsed from prior treatment with immunotherapy, radiotherapy, or surgery to the time of randomization.
- Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0) at the time of randomization.
- Eastern Cooperative Oncology Group (ECOG) performance status >1.
- History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
- Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which treatment has been completed ≥5 years ago and from which the patient has been disease-free for ≥5 years.
- Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization.
- Acquired immunodeficiency syndrome (AIDS)-related illnesses or known Human immunodeficiency virus (HIV) disease requiring antiretroviral treatment.
- Any severe acute or chronic medical condition including uncontrolled diabetes mellitus, severe renal impairment, history of cardiovascular disease (uncontrolled hypertension, arterial thrombotic events in the past 6 months, congestive heart failure, severe or unstable angina pectoris, recent myocardial infraction within last 6 months or uncontrolled cardiac arrhythmia), which could impair the ability of the patient to participate to the study or interfere with interpretation of study results, or patient unable to comply with the study procedures.
- Participants with reproductive potential who do not agree to use accepted and effective method of contraception during the study treatment period and up to 6 months after the last administered dose. The definition of "effective method of contraception" will be based on the Investigator's judgment.
- Known allergies, hypersensitivity or intolerance to prednisone or excipients of abiraterone acetate or enzalutamide. History of hypersensitivity to docetaxel or polysorbate 80.
- Known history of mineralocorticoid excess or deficiency (not applicable to participants who have already been treated with abiraterone acetate in first line before inclusion).
- History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold (not applicable to participants who have already been treated with enzalutamide in first line before inclusion).
- Unable to swallow a whole tablet or capsule.
- Inadequate organ and bone marrow function as evidenced by:
- Hemoglobin <10.0 g/dL.
- Absolute neutrophil count <1.5 x 10^9/L.
- Platelet count <100 x 10^9/L.
- Aspartate aminotransferase (AST) and/or Alanine aminotransferase (ALT) >1.5 x Upper limit of normal (ULN).
- Total bilirubin >1.0 x ULN.
- Potassium <3.5 mmol/L.
- Serum albumin <3.0 g/dL.
- Child-Pugh Class B and C.
- Contraindications to the use of corticosteroid treatment.
- Symptomatic peripheral neuropathy grade ≥2 NCI CTCAE v4.0.
- Concomitant vaccination with yellow fever vaccine.
The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Cabazitaxel
Participants received Cabazitaxel 25 mg/m^2, intravenously for 1 hour along with prednisone 10 mg orally on Day 1 of every treatment cycle (each cycle was of 3 weeks) until disease progression, unacceptable toxicity, or participant's refusal of further study treatment.
|
Otros nombres:
|
|
Comparador activo: Abiraterone acetate or Enzalutamide
Participants received abiraterone acetate 1000 mg (4 tablets of 250 mg), orally once daily along with prednisone 5 mg, orally twice daily from Day 1 to 21 in each treatment cycle (each cycle was of 3 weeks) or enzalutamide 160 mg, orally, until disease progression, unacceptable toxicity, or participant's refusal of further study treatment.
|
Otros nombres:
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Radiographic Progression-Free Survival (rPFS)
Periodo de tiempo: Baseline until tumor progression or bone lesion progression or death due to any cause (maximum duration: 1059 days)
|
rPFS was defined as the time from randomization to the first occurrence of radiological tumor progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or progression of bone lesions using prostate cancer working group 2 (PCWG2) criteria or death due to any cause.
|
Baseline until tumor progression or bone lesion progression or death due to any cause (maximum duration: 1059 days)
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Number of Participants With Prostate Specific Antigen (PSA) Response
Periodo de tiempo: Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days)
|
PSA response was defined as decline of serum PSA from baseline by >= 50 percent (%).
|
Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days)
|
|
Progression-free Survival (PFS)
Periodo de tiempo: Baseline upto progression or death due to any cause (maximum duration: 1059 days)
|
PFS: time interval between date of randomization to first documentation of tumor progression as per RECIST 1.1.
|
Baseline upto progression or death due to any cause (maximum duration: 1059 days)
|
|
Overall Survival
Periodo de tiempo: Baseline until death or study cut-off date, whichever was earlier (maximum duration: 1059 days)
|
Overall Survival was defined as the time interval from the date of randomization to the date of death due to any cause.
|
Baseline until death or study cut-off date, whichever was earlier (maximum duration: 1059 days)
|
|
Time to PSA Progression
Periodo de tiempo: Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days)
|
Time to PSA progression was defined as the time interval between the date of randomization and the date of first documented PSA progression as per PCWG2 criteria.
|
Baseline up to PSA progression or death due to any cause (maximum duration: 1059 days)
|
|
Number of Participants Achieving Tumor Response
Periodo de tiempo: Baseline up to disease progression or death due to any cause (maximum duration: 1059 days)
|
Tumor response was defined as either a partial response (PR) or complete response (CR) according to the RECIST 1.1.
|
Baseline up to disease progression or death due to any cause (maximum duration: 1059 days)
|
|
Duration of Tumor Response
Periodo de tiempo: Baseline up to disease progression or death due to any cause (maximum duration: 1059 days)
|
Duration of tumor response was defined as the time between the first evaluation at which the tumor response criteria were met and the first documentation of tumor progression.
|
Baseline up to disease progression or death due to any cause (maximum duration: 1059 days)
|
|
Pain Response Using Brief Pain Inventory-Short Form (BPI-SF) for Pain Intensity Score
Periodo de tiempo: Baseline until the end of study (maximum duration: 1059 days)
|
Pain response was analyzed using the brief pain inventory-short form (BPI-SF).
|
Baseline until the end of study (maximum duration: 1059 days)
|
|
Time to Pain Progression
Periodo de tiempo: Baseline until disease progression, start of another anticancer therapy or study cut off, whichever came first (maximum duration: 1059 days)
|
Time to pain progression was defined as the time interval between the date of randomization and the date of the first documented pain progression.
|
Baseline until disease progression, start of another anticancer therapy or study cut off, whichever came first (maximum duration: 1059 days)
|
|
Percentage of Participants With Symptomatic Skeletal Event (SSE)
Periodo de tiempo: Baseline until the end of study (maximum duration: 1059 days)
|
SSE was the occurrence of a new symptomatic pathological fracture, or the use of external beam radiation to relieve bone pain, or the occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention.
|
Baseline until the end of study (maximum duration: 1059 days)
|
|
Time to Occurrence of Any Symptomatic Skeletal Events (SSE)
Periodo de tiempo: Baseline up to occurrence of the first event defining a SSE (maximum duration: 1059 days)
|
Time to SSE was defined as the time interval between the date of randomization and the date of the occurrence of the first event defining a SSE, whichever is earlier.
|
Baseline up to occurrence of the first event defining a SSE (maximum duration: 1059 days)
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
17 de junio de 2015
Finalización primaria (Actual)
10 de mayo de 2018
Finalización del estudio (Actual)
10 de mayo de 2018
Fechas de registro del estudio
Enviado por primera vez
27 de febrero de 2015
Primero enviado que cumplió con los criterios de control de calidad
3 de marzo de 2015
Publicado por primera vez (Estimar)
4 de marzo de 2015
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
21 de junio de 2019
Última actualización enviada que cumplió con los criterios de control de calidad
19 de junio de 2019
Última verificación
1 de junio de 2019
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Neoplasias
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias Genitales Masculinas
- Enfermedades prostáticas
- Neoplasias prostáticas
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antiinflamatorios
- Agentes antineoplásicos
- Glucocorticoides
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Agentes Antineoplásicos Hormonales
- Inhibidores de enzimas del citocromo P-450
- Antagonistas de hormonas
- Inhibidores de la síntesis de esteroides
- Prednisona
- Acetato de abiraterona
Otros números de identificación del estudio
- LPS14022
- U1111-1160-6008 (Otro identificador: UTN)
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. .