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Study of Tremelimumab Alone or Combined With Olaparib for Patients With Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)

An Open Label Dose Escalation/Expansion Study of Tremelimumab Alone or Combined With Olaparib for Recurrent or Persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma)

This study will be looking at what dose of tremelimumab and olaparib is safe and effective in patients with persistent EOC (Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma).

Descripción general del estudio

Estado

Terminado

Intervención / Tratamiento

Descripción detallada

This clinical trial was initially intended to be a Phase 1/2 trial, but the trial never moved forward to Phase 2 prior to termination.

Tipo de estudio

Intervencionista

Inscripción (Actual)

24

Fase

  • Fase 1

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

    • Maryland
      • Baltimore, Maryland, Estados Unidos, 21231
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

Todos

Descripción

Inclusion Criteria:

  1. Signed informed consent form
  2. Age ≥ 18 years
  3. Recurrent or persistent EOC (epithelial ovarian, fallopian tube or primary peritoneal carcinoma)
  4. Have archival tissue or willingness to undergo a tumor biopsy
  5. Have measurable disease
  6. Have had one prior taxane-platinum-based chemotherapeutic regimen
  7. Have had a treatment-free interval following platinum-based therapy of less than 12 months, have progressed during platinum-based therapy, or had persistent disease after a platinum-based regimen
  8. Have received hormonal therapy
  9. ECOG Performance Status of 0 to 1
  10. Ability to take oral medications
  11. HIV, HTLV-1, HBV, and HCV negative
  12. Adequate organ and bone marrow function as defined by study-specified laboratory tests
  13. Normal blood coagulation parameters
  14. Life expectancy greater than 16 weeks
  15. Must use acceptable form of birth control through the study and for 28 days after final dose of study drug
  16. Willing and able to comply with study procedures

Exclusion Criteria:

  1. Prior therapy with an anti-CTLA-4 antibody or PARP inhibitor
  2. Active infection requiring antibiotics
  3. Active autoimmune disease
  4. Active and uncontrolled intercurrent illness
  5. History of other cancers within the past 5 years
  6. Systemically active steroid use
  7. Receiving systemic chemotherapy or radiotherapy within 4 weeks prior to the first dose of study drug
  8. Use of ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir
  9. Requirement for chronic parenteral hydration/nutrition
  10. Vaccination with live attenuated vaccine within 1 month prior to first dose of study drug
  11. Patients with untreated brain metastases, treated brain metastases that are not stable, leptomeningeal disease, or seizures uncontrolled with standard medical therapy
  12. Patients with myelodysplastic syndrome/acute myeloid leukaemia
  13. History of diverticulitis
  14. History of bleeding disorder or diathesis.
  15. Serious or nonhealing wound, ulcer, bone fracture, or osteonecrosis of the jaw
  16. Major surgical procedure within 28 days of study enrollment, or anticipated while on study.
  17. Pregnant or breast feeding woman

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: Arm A: Tremelimumab Alone
25 patients will receive tremelimumab alone at 10 mg/kg IV every 4 weeks for 7 doses then every 12 weeks until disease progression.
Experimental: Arm B1: DESE Tremelimumab and Olaparib
18 patients will receive tremelimumab (3 or 10 mg/kg IV) every 4 weeks for 7 doses then every 12 weeks and olaparib (150 or 300 mg orally twice a day) until disease progression.
Otros nombres:
  • LYNPARZA
Experimental: Arm B2: Tremelimumab and Olaparib
25 patients will receive tremelimumab (every 4 weeks for 7 doses then every 12 weeks) and olaparib (daily) until disease progression. Dose of tremelimumab and olaparib will be determined during the DESE (Arm B1).
Otros nombres:
  • LYNPARZA

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Adverse events as a measure of the safety and tolerability profile of tremelimumab in combination with olaparib
Periodo de tiempo: 4 years
Number of participants experiencing study drug-related dose limiting toxicities (DLTs). Dose escalation (phase I) portion of the trial only.
4 years
Fold change from baseline in the ratio of peripheral CD4+ICOShi T cells and Regulatory T cells
Periodo de tiempo: 4 years
Dose escalation (phase I) portion of the trial only.
4 years
Maximum Tolerated Dose (MTD) of tremelimumab combined with olaparib
Periodo de tiempo: 4 years
Dose escalation (phase I) portion of the trial only.
4 years

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Supervivencia general (SG)
Periodo de tiempo: 4 años
La OS se medirá desde la fecha de la primera dosis hasta la muerte o el final del seguimiento (la OS se censurará en la fecha en que se supo por última vez que el sujeto estaba vivo para los sujetos sin documentación de muerte en el momento del análisis). Estimación basada en la curva de Kaplan-Meier.
4 años
Progression Free Survival (PFS) Rate at 6 months by RECIST
Periodo de tiempo: 6 months
PFS rate is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 6 months. Per RECIST 1.1 criteria, Complete Response (CR) = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
6 months
Progression Free Survival (PFS) Rate at 6 months by irRECIST
Periodo de tiempo: 6 months
PFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRECIST criteria) or death due to any cause at 6 months. Per irRECIST criteria, irCR = disappearance of all lesions, irPR is =>30% decrease in tumor burden, irPD is >20% increase in tumor burden compared with nadir, irSD is <30% decrease in tumor burden compared with baseline cannot be established nor <20% increase compared with nadir. Estimation based on the Kaplan-Meier curve.
6 months
Objective Response Rate (ORR) by RECIST
Periodo de tiempo: 4 years
Objective Response Rate (ORR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. Per RECIST 1.1 criteria, CR = disappearance of all target lesions and PR is =>30% decrease in sum of diameters of target lesions.
4 years
Objective Response Rate (ORR) by irRECIST
Periodo de tiempo: 4 years
Objective Response Rate (irORR) is defined as the percentage of patients achieving a complete response (irCR) or partial response (irPR) based on irRECIST criteria. Per irRECIST criteria, irCR = disappearance of all lesions and irPR is =>30% decrease in tumor burden.
4 years
Duration of Response by RECIST
Periodo de tiempo: 4 years
Number of months from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, and PD is >20% increase in sum of diameters of target lesions.
4 years
Duration of Response by irRECIST
Periodo de tiempo: 4 years
Number of months from the start date of irPR or irCR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per irRECIST criteria, irCR = disappearance of all lesions, irPR is =>30% decrease in tumor burden, and irPD is is >20% increase in tumor burden compared with nadir.
4 years
Disease Control Rate (DCR)
Periodo de tiempo: 4 years
DCR is defined as the number of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, PD is >20% increase in sum of diameters of target lesions, SD is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
4 years
Progression-Free Survival (PFS)
Periodo de tiempo: 4 years
PFS is defined as the number of patients with disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
4 years

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Colaboradores

Investigadores

  • Investigador principal: Stéphanie Gaillard, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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)

8 de enero de 2016

Finalización primaria (Actual)

5 de marzo de 2020

Finalización del estudio (Actual)

5 de marzo de 2020

Fechas de registro del estudio

Enviado por primera vez

26 de junio de 2015

Primero enviado que cumplió con los criterios de control de calidad

29 de junio de 2015

Publicado por primera vez (Estimar)

30 de junio de 2015

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

12 de abril de 2021

Última actualización enviada que cumplió con los criterios de control de calidad

9 de abril de 2021

Última verificación

1 de abril de 2021

Más información

Términos relacionados con este estudio

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. .

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