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- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01864538
A Phase 2 Biomarker - Enriched Study of TH-302 in Subjects With Advanced Melanoma
24 de marzo de 2021 actualizado por: Threshold Pharmaceuticals
The primary objective of this study is to determine the response rate, duration of response,progression-free survival and overall survival of subjects with advanced melanoma treated with TH-302.
Descripción general del estudio
Descripción detallada
Hypoxia is an independent marker of a poor prognosis for subjects with metastatic melanoma (Simonetti 2012, Lartigau 1997).
Hypoxic melanoma cells are more likely to exhibit a stem-cell like phenotype with an associated increased propensity for invasion, angiogenesis, and metastasis formation compared to normoxic cells.
Moreover, this phenotype is also associated with treatment resistance.
TH-302, a hypoxia activated prodrug (HAP), was designed to target the hypoxic nature of tumours while having a minimal effect on normoxic tissue.
TH-302 belongs to a class of alkylating agents that have significant experimental and clinical activity (Brock 1989).
Preclinical data support the hypothesis that TH-302 targets hypoxic regions of tumours and is also able to kill tumour cells in normoxic regions as a result of cytotoxin diffusion, leading to significant effects on tumour growth (Meng 2011).
TH-302 has been investigated in over 700 subjects with solid tumours or hematologic malignancies, including subjects with metastatic melanoma.
In this subset a disease control rate of 63% (3 subjects with partial responses and 9 subjects with stable disease out of a total of 19) was observed in an early phase clinical trial of TH-302 (Weber 2010).
Predictive biomarkers for response and toxicity have yet to be identified for subjects with advanced melanoma treated with TH-302.
Optimal patient selection may be critical to maximize the clinical benefit.
A predictive biomarker approach will be investigated to try to identify subjects most likely to benefit from TH-302.
Given the hypoxia-targeting mechanism of TH- 302, it is believed that hypoxia biomarkers will be the most informative for identifying subjects likely to benefit from TH- 302; however, additional biomarkers including DNA repair biomarkers will also be investigated.
In addition, this approach will also have potential to synergise with future immunotherapeutic approaches as suppressive T regulatory cells are thought to reside within hypoxic niches within the tumour microenvironment that would be amenable to targeting by TH-302.
Tipo de estudio
Intervencionista
Inscripción (Actual)
11
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
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Alberta
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Edmonton, Alberta, Canadá, T6G1Z2
- Cross Cancer Institute
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Ontario
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Hamilton, Ontario, Canadá, L8V5C2
- Juravinski Cancer Centre
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London, Ontario, Canadá, N6A4L6
- London Health Sciences Centre
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Toronto, Ontario, Canadá, M5G2M9
- Princess Margaret Hospital
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California
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Los Angeles, California, Estados Unidos, 90025
- The Angeles Clinic and Research Institute
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Los Angeles, California, Estados Unidos, 90404
- UCLA
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New York
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New York, New York, Estados Unidos, 10032
- Columbia University Medical Center
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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:
- At least 18 years of age
- Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's Regional Ethics Board/Independent Ethics Committee (REB/IEC)
- Histologically documented cutaneous or mucosal malignant melanoma, which is recurrent or metastatic and is not curable by surgical or other means.
- Adequate tumour tissue (greater than 0.5cm3 preferred, 3 X core biopsy acceptable) available and agreement from subjects that this tissue from their primary and/or metastatic tumour be made available for assessment of potential biomarkers.
- Ability and availability to complete all prescribed biomarker studies (Screening and after Cycle 2).
- Recovered to Grade 1 from reversible toxicities of prior therapy
- Presence of clinically and/or radiologically documented disease. At least one site of disease (which will not be removed during the course of the study) must be uni-dimensionally measurable as per RECIST 1.1 or clinically quantifiable (such as in the case of skin disease)
- ECOG performance status of 0 - 1.
- Prior treatment with any number of immunotherapies (e.g., IL2, ipilimumab), targeted therapies (e.g., vemurafenib) are permitted but no more than one 1 prior chemotherapy
- Acceptable liver function
- Acceptable renal function
- Acceptable hematologic status (without growth factor support for neutropenia or transfusion dependency):
- Normal 12-lead ECG (clinically insignificant abnormalities permitted)
- Female subjects of childbearing age must have a negative urine HCG test unless prior hysterectomy or menopause (defined as age above 55 and twelve months without menstrual activity). Female subjects should not become pregnant or breast-feed while on this study. Sexually active male and female subjects should use effective birth control.
Exclusion Criteria:
- Anticancer treatment with radiation therapy, targeted therapies, chemotherapy, immunotherapy, hormones or other antitumour therapies within 28 days prior to first dose of TH-302.
- Subjects who have received any other investigational drug or agent within 28 days of first dose of TH-302
- Current use of drugs with known cardiotoxicity
- Significant cardiac dysfunction:
- Seizure disorders requiring anticonvulsant therapy
- Progressing brain metastases (unless previously treated and stable disease for a period of greater than or equal to 3 months on repeat MRI following definitive treatment).
- History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for greater than 2 years
- Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation less than 90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause hypoxia of normal tissue.
- Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1, without complete recovery
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Prior therapy with an hypoxic cytotoxin
- Known infection with HIV or active infection with hepatitis B or hepatitis C
- History of allergic reaction to a structural compound or biological agent similar to TH-302
- Pregnancy or breast-feeding
- Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
- Unwillingness or inability to comply with the study protocol for any reason.
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: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: TH-302
480 mg/m2 by iv infusion over 30 - 60 min on Days 1, 8, and 15 of a 28-day cycle.
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480 mg/m2 by iv infusion over 30 - 60 min on Days 1, 8, and 15 of a 28-day cycle.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
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Sobrevivencia promedio
Periodo de tiempo: 1 año
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1 año
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Director de estudio: Tillman Pearce, MD, Threshold Pharmaceuticals
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)
1 de mayo de 2013
Finalización primaria (Actual)
1 de septiembre de 2015
Finalización del estudio (Actual)
1 de septiembre de 2015
Fechas de registro del estudio
Enviado por primera vez
13 de mayo de 2013
Primero enviado que cumplió con los criterios de control de calidad
24 de mayo de 2013
Publicado por primera vez (Estimar)
29 de mayo de 2013
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
26 de marzo de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
24 de marzo de 2021
Última verificación
1 de agosto de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- TH-CR-413
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. .
Ensayos clínicos sobre TH-302
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Sarcoma Alliance for Research through CollaborationThreshold PharmaceuticalsYa no está disponibleSarcoma de tejido blando
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Threshold PharmaceuticalsDesconocidoTumores sólidosEstados Unidos
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Threshold PharmaceuticalsTerminadoHipoxia | TumoresEstados Unidos
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Threshold PharmaceuticalsTerminadoLeucemia linfoblástica aguda | Leucemia linfocítica crónica | Leucemia mielógena aguda | Leucemia mielógena crónica | Síndrome mielodisplásico de alto riesgo | Mielofibrosis avanzadaEstados Unidos
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Seoul National University HospitalThreshold PharmaceuticalsTerminadoCáncer de vías biliaresCorea, república de
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Herbert Hurwitz, MDGlaxoSmithKline; National Comprehensive Cancer Network; Threshold PharmaceuticalsTerminado
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Merck KGaA, Darmstadt, GermanyThreshold PharmaceuticalsTerminado
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Threshold PharmaceuticalsTerminadoSarcoma de tejido blandoEstados Unidos
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Threshold PharmaceuticalsDesconocidoTumores del estroma gastrointestinal | Carcinoma avanzado de células renales | Tumores neuroendocrinos pancreáticosEstados Unidos
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Threshold PharmaceuticalsTerminadoCancer de pancreas | Cáncer de pulmón de células no pequeñas | Cancer de prostataEstados Unidos