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Prueba de la respuesta al fármaco contra el cáncer, triapina, en cánceres de útero utilizando marcadores del tejido en el momento de la histerectomía

11 de noviembre de 2026 actualizado por: National Cancer Institute (NCI)

Un ensayo farmacodinámico de ventana de oportunidad de fase 0 de triapina (NSC# 663249) en el adenocarcinoma seroso del cuerpo uterino

This early phase I trial investigates the response to the anti-cancer drug, triapine, in uterine cancers by using markers from tissue samples at the time of removal of the uterus, ovaries, and fallopian tubes (hysterectomy and bilateral salpingo-oophorectomy). Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Adding triapine to the usual approach of surgery followed by chemotherapy alone or in combination with radiation therapy may help to slow the growth of uterine cancer.

Descripción general del estudio

Estado

Activo, no reclutando

Condiciones

Intervención / Tratamiento

Descripción detallada

PRIMARY OBJECTIVE:

I. Determine whether intravenous (IV) triapine 25 mg/m^2 will induce cell cycle arrest as measured by phospho-histone H3 (pHH3) in uterine serous adenocarcinoma cells removed at the time of hysterectomy.

SECONDARY OBJECTIVES:

I. Determine whether a preoperative dose of intravenous triapine 25 mg/m^2 can be safely given prior to hysterectomy and staging for uterine serous adenocarcinoma.

II. Determine whether changes in cyclin D/E and Ki-67 protein expression are detectable using immunohistochemistry pre- and post-triapine treatment in uterine serous adenocarcinomas.

III. Evaluate plasma and tissue triapine concentrations.

EXPLORATORY OBJECTIVES:

I. Determine the feasibility of using single-cell transcriptome analysis to quantify changes in gene expression following triapine treatment and to evaluate their concordance with immunohistochemistry (IHC) endpoints of cell cycle arrest.

II. Identify genomic variants of uterine serous adenocarcinoma (including but not limited to p53) with treatment response to ribonucleotide reductase inhibitors such as triapine using whole exome sequencing (WES).

OUTLINE:

Patients receive triapine IV over 2 hours on day 1. Patients then undergo surgical resection and tissue collection 6-8 hours after the initiation of the triapine infusion. Patients also undergo biopsy and collection of blood samples on study.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

12

Fase

  • Fase temprana 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

    • Florida
      • Coral Gables, Florida, Estados Unidos, 33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Deerfield Beach, Florida, Estados Unidos, 33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Miami, Florida, Estados Unidos, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Plantation, Florida, Estados Unidos, 33324
        • UM Sylvester Comprehensive Cancer Center at Plantation
    • Maryland
      • Baltimore, Maryland, Estados Unidos, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19107
        • Thomas Jefferson University Hospital
    • Virginia
      • Richmond, Virginia, Estados Unidos, 23298
        • VCU Massey Comprehensive Cancer Center

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

Femenino

Descripción

Inclusion Criteria:

  • Patients must have histologically confirmed uterine corpus serous adenocarcinoma
  • Patients must be planned for surgical hysterectomy and operative staging
  • Patients must have adequate archival tissue obtained within 8 weeks of step 1 registration OR have sufficient tumor tissue and be willing to undergo an endometrial pipelle biopsy prior to beginning study treatment.
  • Patients must have adequate primary tumor volume, as determined by imaging (e.g., computed tomography [CT], ultrasound, magnetic resonance imaging [MRI]) at eligibility screening, to accommodate research specimen collections in addition to clinical pathology evaluation
  • Patients must not have received any prior anticancer treatment for endometrial cancer
  • Patients must be >= 18 years old. Because no dosing or adverse event data are currently available on the use of triapine in patients < 18 years of age, children are excluded from this study
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
  • International normalized ratio (INR) =< 2
  • Creatinine =< 1.5 x institutional ULN OR glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Patients of childbearing potential must have a negative pregnancy test result prior to beginning study treatment
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) are not eligible as there is limited likelihood of direct benefit for participants in this study

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
  • Patients who are receiving any other investigational agents
  • Patients who have known brain metastases, as they are not candidates for surgery
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine
  • Patients receiving any medications or substances that are inhibitors or inducers of triapine, as well as medications known to be associated with methemoglobinemia, are ineligible. Triapine drug interactions have not yet been identified. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Patients with uncontrolled intercurrent illness
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are not eligible. Patients at risk for G6PD deficiency must be screened prior to enrollment

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
Experimental: Treatment (triapine, surgical resection)

Patients receive triapine IV over 2 hours on day 1. Patients then undergo surgical resection and tissue collection 6-8 hours after the initiation of the triapine infusion. Patients also undergo biopsy and collection of blood samples on study.

Undergo biopsy

Otros nombres:
  • Caja
  • BIOPSIA_TIPO
  • Biopsia

Undergo collection of tissue and blood samples

Otros nombres:
  • Recolección de muestras biológicas
  • Muestra biológica recolectada
  • Coleccion de especimenes
  • Recolección de muestras

Undergo surgical resection

Otros nombres:
  • Resección quirúrgica

Given IV

Otros nombres:
  • 3-aminopiridina-2-carboxaldehído tiosemicarbazona
  • 3-AP
  • 3-Apto
  • OCX-0191
  • OCX-191
  • OCX191
  • PAN-811

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Pharmacodynamic response
Periodo de tiempo: Up to 6-8 hours post-triapine infusion

Pharmacodynamic response rate will be estimated as the proportion of evaluable patients who achieve pharmacodynamic response defined as a decrease in phospho-histone H3 immunoscore of >= 1 from baseline to post-exposure of intravenous triapine for each patient. The corresponding 95% confidence interval will be provided.

Up to 6-8 hours post-triapine infusion

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Incidence of adverse events
Periodo de tiempo: Up to day 42

Dose-limiting toxicities, as listed by Common Terminology Criteria for Adverse Events, version 5, are defined as any pre-surgical grade 3 or higher non-hematologic toxicity or grade 4 neutropenia, neutropenic fever, or thrombocytopenia within 24 hours of triapine administration. Toxicity will be tabulated by type and grade.

Up to day 42
Pharmacokinetic (PK) analysis
Periodo de tiempo: Baseline, 5 minutes before end of triapine infusion, 6-8 hours post-infusion (at time of surgical tissue resection), and 24 hours post-infusion

End of infusion plasma concentrations represent maximum concentration and will be compared with historical data. Post-triapine plasma and tissue concentrations will generate plasma to tissue ratios, which represent the tissue partitioning coefficient, a useful PK parameter.

Baseline, 5 minutes before end of triapine infusion, 6-8 hours post-infusion (at time of surgical tissue resection), and 24 hours post-infusion

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
Single-cell transcriptome analysis
Periodo de tiempo: Baseline, post-triapine infusion, surgical resection

Single-cell transcriptome analysis will be conducted to quantify changes in gene expression following triapine treatment. Changes of gene expression will be correlated with immunohistochemistry endpoints of cell cycle arrest.

Baseline, post-triapine infusion, surgical resection
Whole exome sequencing (WES) analysis
Periodo de tiempo: Baseline

WES will be used to identify genomic variants of uterine serous adenocarcinoma (including but not limited to p53) that can predict the treatment response to triapine.

Baseline

Colaboradores e Investigadores

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

Patrocinador

Investigadores

  • Investigador principal: Rebecca L Stone, JHU Sidney Kimmel Comprehensive Cancer Center LAO

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 febrero de 2022

Finalización primaria (Estimado)

30 de noviembre de 2026

Finalización del estudio (Estimado)

30 de noviembre de 2026

Fechas de registro del estudio

Enviado por primera vez

30 de julio de 2020

Primero enviado que cumplió con los criterios de control de calidad

30 de julio de 2020

Publicado por primera vez (Actual)

31 de julio de 2020

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

12 de noviembre de 2026

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

11 de noviembre de 2026

Última verificación

1 de junio de 2026

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • NCI-2020-05457
  • UM1CA186691 (Subvención/contrato del NIH de EE. UU.)
  • NCI-2020-05457 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
  • 10401 (Otro identificador: CTEP)
  • 10401 (Otro identificador: JHU Sidney Kimmel Comprehensive Cancer Center LAO)

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Descripción del plan IPD

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

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. .