Radioterapia con protones o fotones en el tratamiento de pacientes con cáncer de hígado
Un ensayo aleatorizado de fase III de protones versus fotones para el carcinoma hepatocelular
This phase III trial studies how well radiation therapy with protons works compared with photons in treating patients with liver cancer. Radiation therapy, such as photon therapy, uses high energy x-rays to send the radiation inside the body to the tumor while proton therapy uses a beam of proton particles. Proton therapy can stop shortly after penetrating through the tumor and may cause less damage to the surrounding healthy organs and result in better survival in patients with liver cancer.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
PRIMARY OBJECTIVE:
I. To determine if overall survival (OS) is different for hepatocellular carcinoma patients treated with protons compared to photons.
SECONDARY OBJECTIVES:
I. To determine the difference in progression-free-survival (PFS) in patients with hepatocellular carcinoma (HCC) treated with protons compared to patients with HCC treated with photons.
II. To determine the difference in local progression (LP) in patients with HCC treated with protons compared to patients with HCC treated with photons.
III. To determine differences in toxicity in patients with HCC treated with protons versus photons.
IV. To determine differences in fatigue, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue in patients with HCC treated with protons, versus photons; as well as quality-adjusted survival, if the primary endpoint is met.
V. To determine if there are correlations between the baseline values of hepatocyte growth factor (HGF) and outcomes (OS/PFS/fatigue).
EXPLORATORY OBJECTIVES:
I. To determine differences in overall quality of life, measured by Functional Assessment of Cancer Therapy-Hepatobiliary Cancer (FACT-Hep) in patients with HCC treated with protons.
II. Biospecimen collection for future correlative science projects.
OUTLINE: Patients are randomized to 1 of 2 arms, photon or proton therapy (see Arms and Interventions).
Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly thereafter.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Georgia
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Atlanta, Georgia, Estados Unidos, 30308
- Emory University Hospital Midtown
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Atlanta, Georgia, Estados Unidos, 30322
- Emory University Hospital/Winship Cancer Institute
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Atlanta, Georgia, Estados Unidos, 30342
- Emory Saint Joseph's Hospital
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Atlanta, Georgia, Estados Unidos, 30308
- Emory Proton Therapy Center
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Illinois
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Warrenville, Illinois, Estados Unidos, 60555
- Northwestern Medicine Cancer Center Warrenville
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Maryland
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Baltimore, Maryland, Estados Unidos, 21201
- University of Maryland/Greenebaum Cancer Center
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Baltimore, Maryland, Estados Unidos, 21201
- Maryland Proton Treatment Center
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital Cancer Center
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Michigan
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Dearborn, Michigan, Estados Unidos, 48124
- Corewell Health Dearborn Hospital
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Royal Oak, Michigan, Estados Unidos, 48073
- Corewell Health William Beaumont University Hospital
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Troy, Michigan, Estados Unidos, 48085
- Corewell Health Beaumont Troy Hospital
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Missouri
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St Louis, Missouri, Estados Unidos, 63110
- Washington University School of Medicine
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New Jersey
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Basking Ridge, New Jersey, Estados Unidos, 07920
- Memorial Sloan Kettering Basking Ridge
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Middletown, New Jersey, Estados Unidos, 07748
- Memorial Sloan Kettering Monmouth
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Montvale, New Jersey, Estados Unidos, 07645
- Memorial Sloan Kettering Bergen
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New York
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Commack, New York, Estados Unidos, 11725
- Memorial Sloan Kettering Commack
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East White Plains, New York, Estados Unidos, 10604
- Memorial Sloan Kettering Westchester
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New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Estados Unidos, 10035
- New York Proton Center
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Uniondale, New York, Estados Unidos, 11553
- Memorial Sloan Kettering Nassau
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45219
- University of Cincinnati Cancer Center-UC Medical Center
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Cleveland, Ohio, Estados Unidos, 44106
- Case Western Reserve University
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Columbus, Ohio, Estados Unidos, 43210
- Ohio State University Comprehensive Cancer Center
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West Chester, Ohio, Estados Unidos, 45069
- University of Cincinnati Cancer Center-West Chester
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Texas
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Houston, Texas, Estados Unidos, 77030
- UT MD Anderson Cancer Center
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Washington
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Seattle, Washington, Estados Unidos, 98195
- University of Washington Medical Center - Montlake
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Seattle, Washington, Estados Unidos, 98109
- Fred Hutchinson Cancer Center
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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Pathologically (histologically or cytologically) or radiographically-proven (based on the American Association for the Study of Liver Diseases [AALSD] criteria) unresectable or locally recurrent hepatocellular cancer prior to registration
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Appropriate stage for study entry based on the following diagnostic workup:
- All patients must have computed tomography (CT) scan chest/abdomen/pelvis with multiphasic liver CT scan prior to registration; if CT contrast is contraindicated, CT chest without contrast and magnetic resonance imaging (MRI) of abdomen is permitted
- Participants must have measurable disease at study entry, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 2 cm with conventional techniques or as > 1 cm with spiral CT scan
- Patient must have 3 or fewer single or multinodular tumors; for patients with a single lesion, lesion must be 15 cm or less in greatest dimension; for patients with two lesions, no lesion may be greater than 10 cm in greatest dimension; for patients with three lesions, no lesion may be greater than 6 cm in greatest dimension; portal vein involvement or thrombosis combined with a single lesion that is >= 1 cm and =< 15 cm in greatest dimension is allowed
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Age >= 18
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Zubrod performance status 0-1 within 30 days prior to registration
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Negative urine or serum pregnancy test for women of childbearing potential within 7 days prior to study entry
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Absolute neutrophil count (ANC) >= 1,000 cells/mm^3
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Platelets >= 50,000 cells/mm^3
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Hemoglobin >= 9.0 g/dl; (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable)
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Total bilirubin < 4 x institutional upper limit of normal (ULN)
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Transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) < 6 x institutional ULN
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Albumin >= 2.5 g/dl
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Creatinine < 2 mg/dl
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Prior chemotherapy, targeted biological therapy (e.g. sorafenib), surgery, transarterial chemoembolization (TACE), ablation for present disease is acceptable
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Must have Child-Turcotte-Pugh (CTP) A or B7
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The patient or a legally authorized representative must provide study-specific informed consent prior to study registration
Exclusion Criteria:
- PRIOR TO STEP ONE REGISTRATION:
- Definitive clinical or radiologic documentation of extrahepatic tumor, defined as extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) > 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions); note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
- Uncontrolled prior invasive malignancy, excluding the current diagnosis
- Systemic chemotherapy for the study cancer < 2 weeks prior to registration
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
- HIV positive with CD4 count < 200 cells/microliter; note that patients who are human immunodeficiency virus (HIV) positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 (cluster of differentiation 4)count >= 200 cells/microliter prior to registration; note also that HIV testing is not required for eligibility for this protocol; this exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields (to include Y90)
- Prior liver transplant
- PRIOR TO STEP TWO RANDOMIZATION:
- Unable to obtain confirmation of payment coverage (insurance or other) for either possible treatment
Plan de estudios
¿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 |
|---|---|
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Experimental: Proton Therapy (Arm 1)
Proton therapy delivered in 5 fractions over 15 days or 15 fractions over 24 days, determined by the treating physician. |
Fractions
Otros nombres:
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Experimental: Photon Therapy (Arm 2)
Photon therapy delivered in 5 fractions over 15 days or 15 fractions over 24 days, determined by the treating physician. |
Fractions
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percentage of Participants Alive (Overall Survival)
Periodo de tiempo: From randomization to death or last follow-up. Median follow-up time for all patients at time of analysis was 20.4 months. One- and two-year estimates are reported.
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Survival rates are estimated using the Kaplan-Meier method, censoring participants alive at last known follow-up. |
From randomization to death or last follow-up. Median follow-up time for all patients at time of analysis was 20.4 months. One- and two-year estimates are reported.
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percentage of Participants Alive Without Progression (Progression-free Survival)
Periodo de tiempo: From randomization to progression, death, or last follow-up, whichever occurs first. Median follow-up time for all patients at time of analysis was 20.4 months. One- and two-year estimates are reported.
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Progression is defined as local, regional, or distant progression. Progression-free survival rates are estimated using the Kaplan-Meier method, censoring participants alive without progression at time of last follow-up. |
From randomization to progression, death, or last follow-up, whichever occurs first. Median follow-up time for all patients at time of analysis was 20.4 months. One- and two-year estimates are reported.
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Percentage of Participants With Local Progression
Periodo de tiempo: From randomization to local progression, death, or last follow-up, whichever occurs first. Median follow-up time for all patients at time of analysis was 20.4 months. One- and two-year estimates are reported.
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Local progression rates are estimated using the cumulative incidence method in which death is treated as competing risk and participants alive without local failure are censored at last known follow-up. |
From randomization to local progression, death, or last follow-up, whichever occurs first. Median follow-up time for all patients at time of analysis was 20.4 months. One- and two-year estimates are reported.
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Percentage of Participants With Grade 3+ Treatment-Related Adverse Events
Periodo de tiempo: From randomization to death or last follow-up. Median follow-up time for all patients at time of analysis was 20.4 months.
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Common Terminology Criteria for Adverse Events (version 5.0) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Adverse events reported as possibly, probably, or definitely related to treatment are considered to be treatment-related adverse events. |
From randomization to death or last follow-up. Median follow-up time for all patients at time of analysis was 20.4 months.
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Change From Baseline to One Month in the Patient Reported Outcomes Measurement Information System - Fatigue Short Form version1.0 8a [PROMIS Fatigue Score]
Periodo de tiempo: Baseline and one month
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The PROMIS Fatigue Short Form v1.0 8a contains 8 items that assess self-reported fatigue symptoms over the past 7 days. Item responses are summed to obtain a raw score ranging from 8 to 40, which is then converted to a standardized T-score (mean = 50, standard deviation = 10). Higher T-scores indicate greater fatigue. Change from baseline is calculated as the post-baseline T-score minus the baseline T-score, with positive change scores indicating increased fatigue and negative change scores indicating decreased fatigue. |
Baseline and one month
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Quality-adjusted LIfe Years
Periodo de tiempo: Baseline up to 12 months
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Was to be calculated using the EuroQol 5-Dimension Three Level Questionnaire (EQ-5D-3L). |
Baseline up to 12 months
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Percentage of Participants Alive (Overall Survival) by Plasma Hepatocyte Growth Factor (HGF) Level
Periodo de tiempo: From randomization to death or last follow-up. One- and two-year estimates will be reported.
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Survival rates are estimated using the Kaplan-Meier method, censoring participants alive at last known follow-up. HGF will be dichotomized at 2311 pg/mL. |
From randomization to death or last follow-up. One- and two-year estimates will be reported.
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Percentage of Participants Alive Without Progression (Progression-free Survival) by HGF Level
Periodo de tiempo: From randomization to progression, death, or last follow-up, whichever occurs first. One- and two-year estimates will be reported.
|
Progression is defined as local, regional, or distant progression. Progression-free survival rates are estimated using the Kaplan-Meier method, censoring participants alive without progression at time of last follow-up. HGF will be dichotomized at 2311 pg/mL. |
From randomization to progression, death, or last follow-up, whichever occurs first. One- and two-year estimates will be reported.
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Change From Baseline to One Month in PROMIS Fatigue Score by HGF Level
Periodo de tiempo: Baseline and one month
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The PROMIS Fatigue Short Form v1.0 8a contains 8 items that assess self-reported fatigue symptoms over the past 7 days. Item responses are summed to obtain a raw score ranging from 8 to 40, which is then converted to a standardized T-score (mean = 50, standard deviation = 10). Higher T-scores indicate greater fatigue. Change from baseline is calculated as the post-baseline T-score minus the baseline T-score, with positive change scores indicating increased fatigue and negative change scores indicating decreased fatigue. HGF will be dichotomized at 2311 pg/mL. |
Baseline and one month
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Overall Quality of Life by Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Version 4
Periodo de tiempo: Baseline up to 12 months
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Differences between treatment arms in the overall score, the four domains (physical, social, emotional, and functional well-being), and the additional concerns subscale will also be analyzed. |
Baseline up to 12 months
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Title: Percentage of Participants Alive (Overall Survival) by Sex
Periodo de tiempo: From randomization to death or last follow-up. Median follow-up for all patients at time of analysis was 20.4 months. Two-year estimates are reported.
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NIH-required analysis. Survival rates are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis. |
From randomization to death or last follow-up. Median follow-up for all patients at time of analysis was 20.4 months. Two-year estimates are reported.
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Percentage of Participants Alive (Overall Survival) by Race
Periodo de tiempo: From randomization to death or last follow-up. Median follow-up time for all patients at time of analysis was 20.4 months. Two-year estimates are reported.
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NIH-required analysis. Survival rates are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis. |
From randomization to death or last follow-up. Median follow-up time for all patients at time of analysis was 20.4 months. Two-year estimates are reported.
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Percentage of Participants Alive (Overall Survival) by Ethnicity
Periodo de tiempo: From randomization to death or last follow-up. Median follow-up time for all patients at time of analysis was 20.4 months. Two-year estimates are reported.
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NIH-required analysis. Survival rates are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis. |
From randomization to death or last follow-up. Median follow-up time for all patients at time of analysis was 20.4 months. Two-year estimates are reported.
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Theodore S Hong, NRG Oncology
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
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
Términos MeSH relevantes adicionales
- Neoplasias por sitio
- Neoplasias
- Neoplasias por tipo histológico
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades del HIGADO
- Neoplasias Glandulares y Epiteliales
- Adenocarcinoma
- Neoplasias Hepaticas
- Carcinoma
- Carcinoma Hepatocelular
- Terapéutica
- Fenómeno físico
- Radioterapia de iones pesados
- Radioterapia
- Radiación
- Terapia de protones
Otros números de identificación del estudio
- NRG-GI003
- U10CA180868 (Subvención/contrato del NIH de EE. UU.)
- NRG-GI003 (Otro identificador: CTEP)
- NCI-2016-02009 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- NRG-GI003 (Otro identificador: NRG Oncology)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
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Información sobre medicamentos y dispositivos, documentos del estudio
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Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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