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- Ensayo clínico NCT00954512
Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Participants With Advanced Solid Tumors (P04722, MK-7454-004)
A Dose-Escalation Study to Evaluate the Safety and Tolerability of SCH 717454 in Combination With Different Treatment Regimens in Subjects With Advanced Solid Tumors (Phase 1B/2; Protocol No. P04722)
This is a Phase 1B/2, non-randomized, dose-escalation, multicenter, open-label study designed to evaluate the safety and tolerability of robatumumab (SCH 717454, MK-7454) in combination with standard treatment in participants with advanced solid tumors to be conducted in conformance with Good Clinical Practices.
Six different treatment regimens will be investigated in combination with robatumumab.
The study will be divided into two parts. Part 1 will consist of initial safety evaluation and dose-finding of robatumumab in combination with each treatment regimen. Part 2 will consist of an expansion of each robatumumab regimen at a newly established dose level, to better define safety, tolerability, and initial efficacy in specific target populations.
Descripción general del estudio
Estado
Condiciones
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Be willing and able to provide written informed consent for the study.
- Be ±18 years of age of either sex and of any race/ethnicity;
- Part 1: Have a histologically or cytologically confirmed advanced malignant solid tumor;
- Part 2: Have a histologically or cytologically confirmed, with measurable disease (as defined by Response Evaluation Criteria in Solid Tumors [RECIST]), advanced, malignant solid tumor.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of <=2.
- Have adequate organ function within 3 weeks prior to first study drug administration.
Exclusion Criteria:
- Not have known treated or untreated leptomeningeal metastasis or a metastatic central nervous system lesion.
- Not have a history of another malignancy
- Not have received prior therapy with any anti-insulin-like growth factor receptor 1 (anti-IGF-1R) monoclonal antibody.
- Not have received radiation therapy within 2 weeks prior to first study drug administration.
- Not have received radiation therapy to >25% of his/her total bone marrow during his/her lifetime.
- Not have undergone major surgery within 3 weeks prior to first study drug administration.
- Not have known human immunodeficiency virus (HIV) infection or a known HIV-related malignancy.
- Not have known active hepatitis B or C.
- Not have any serious or uncontrolled infection.
- Not have uncontrolled diabetes mellitus.
- Not have had any of the following within 6 months prior to first study drug administration: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality, cerebrovascular accident or transient ischemic attack, or seizure disorder.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Regimen A: FOLFIRI (± Cetuximab) + Robatumumab
Participants with colorectal adenocarcinoma receive FOLFIRI (Irinotecan 180 mg/m^2+ folinic acid 400 mg/m^2+ 5-fluorouracil [5-FU] 400 mg/m^2 bolus followed by 2400 mg/m^2 intravenous [IV] infusion over 46 hours) (± cetuximab initial dose of 400 mg/m^2 IV followed by once-weekly doses of 250 mg/m^2 IV) PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 2-week cycle.
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In Part 1, robatumumab was to be administered at 10 mg/kg, 15 mg/kg (for Regimens B and C), or 20 mg/kg together with the assigned standard treatment.
For Part 2, robatumumab was to be administered at the dose selected during Part 1, based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK) and pharmacodynamic (PD) data.
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Experimental: Regimen B: Carboplatin + Paclitaxel + Robatumumab
Participants with non-small cell lung cancer receive carboplatin administered at an area under the curve (AUC) of 6 mg/mL/min IV PLUS paclitaxel 225 mg/m^2 IV PLUS robatumumab 15 mg/kg IV on Day 1 of each 3-week cycle.
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In Part 1, robatumumab was to be administered at 10 mg/kg, 15 mg/kg (for Regimens B and C), or 20 mg/kg together with the assigned standard treatment.
For Part 2, robatumumab was to be administered at the dose selected during Part 1, based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK) and pharmacodynamic (PD) data.
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Experimental: Regimen C: Epirubicin + Cisplatin + 5-FU + Robatumumab
Participants with gastric adenocarcinoma receive epirubicin 50 mg/m^2 IV PLUS cisplatin 60 mg/m^2 IV PLUS 5-FU 200 mg/m^2/day administered via a 21-week continuous IV infusion PLUS robatumumab 15 mg/kg IV on Day 1 of each 3-week cycle.
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In Part 1, robatumumab was to be administered at 10 mg/kg, 15 mg/kg (for Regimens B and C), or 20 mg/kg together with the assigned standard treatment.
For Part 2, robatumumab was to be administered at the dose selected during Part 1, based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK) and pharmacodynamic (PD) data.
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Experimental: Regimen D: Trastuzumab + Robatumumab
Participants with human epidermal growth factor receptor 2 positive (Her2+) breast cancer receive trastuzumab 4 mg/kg IV once every week PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle.
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In Part 1, robatumumab was to be administered at 10 mg/kg, 15 mg/kg (for Regimens B and C), or 20 mg/kg together with the assigned standard treatment.
For Part 2, robatumumab was to be administered at the dose selected during Part 1, based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK) and pharmacodynamic (PD) data.
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Experimental: Regimen E: mTor Inhibitor (Everolimus) + Robatumumab
Participants with renal cell cancer receive mammalian target of rapamycin (mTor) inhibitor (everolimus) 10 mg orally once per day PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle.
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In Part 1, robatumumab was to be administered at 10 mg/kg, 15 mg/kg (for Regimens B and C), or 20 mg/kg together with the assigned standard treatment.
For Part 2, robatumumab was to be administered at the dose selected during Part 1, based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK) and pharmacodynamic (PD) data.
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Experimental: Regimen F: Gemcitabine (± Erlotinib) + Robatumumab
Participants with pancreatic adenocarcinoma receive gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 in Cycle 1 and on Days 1, 8 and 15 in subsequent cycles (± erlotinib 100 mg per day orally) PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle.
(Cycle 1 is 8 weeks.)
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In Part 1, robatumumab was to be administered at 10 mg/kg, 15 mg/kg (for Regimens B and C), or 20 mg/kg together with the assigned standard treatment.
For Part 2, robatumumab was to be administered at the dose selected during Part 1, based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK) and pharmacodynamic (PD) data.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response
Periodo de tiempo: Up to ~30 days after the final dose of robatumumab (Up to ~14 months)
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Overall best response was determined by RECIST criteria.
Types of overall response could be: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Assessable (NA) or Incomplete Response/Stable Disease (IR/SD).
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Up to ~30 days after the final dose of robatumumab (Up to ~14 months)
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Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs)
Periodo de tiempo: Up to ~30 days after the final dose of robatumumab (Up to ~14 months)
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An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to this study drug.
AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
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Up to ~30 days after the final dose of robatumumab (Up to ~14 months)
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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 (Estimar)
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
- Neoplasias
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de enzimas
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes Protectores
- Inhibidores de la topoisomerasa II
- Inhibidores de la topoisomerasa
- Agentes antineoplásicos inmunológicos
- Micronutrientes
- Antibióticos, Antineoplásicos
- Vitaminas
- Inhibidores de la topoisomerasa I
- Antídotos
- Complejo de vitamina B
- Hematínicos
- Gemcitabina
- Carboplatino
- Trastuzumab
- Epirubicina
- Leucovorina
- Irinotecán
- Levoleucovorina
- Ácido fólico
- Everolimus
- Cetuximab
Otros números de identificación del estudio
- P04722
- MK-7454-004 (Otro identificador: Merck Protocol Number)
- 2009-011101-16 (Número EudraCT)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Datos del estudio/Documentos
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