- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00645710
Infusión arterial hepática de floxuridina, clorhidrato de gemcitabina y terapia con anticuerpos monoclonales radiomarcados para el tratamiento de metástasis hepáticas en pacientes con cáncer colorrectal metastásico tratados previamente con cirugía
Un ensayo de fase I/II de radioinmunoterapia (Y-90 cT84.66), gemcitabina e infusión arterial hepática de Fudr para el carcinoma colorrectal metastásico al hígado
RATIONALE: Drugs used in chemotherapy, such as floxuridine and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hepatic arterial infusion uses a catheter to carry cancer-killing substances directly into the liver. Radiolabeled monoclonal antibodies can find tumor cells and carry tumor-killing substances to them without harming normal cells. Giving hepatic arterial infusion of floxuridine together with gemcitabine hydrochloride and radiolabeled monoclonal antibody therapy after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase I/II trial is studying the side effects and best dose of floxuridine when given as a hepatic arterial infusion together with gemcitabine hydrochloride and radiolabeled monoclonal antibody therapy and to see how well it works in treating liver metastases in patients with metastatic colorectal cancer.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
- Otro: laboratory biomarker analysis
- Otro: pharmacological study
- Droga: gemcitabine hydrochloride
- Droga: floxuridine
- Genético: proteomic profiling
- Otro: matrix-assisted laser desorption/ionization time of flight mass spectrometry
- Otro: liquid chromatography
- Radiación: yttrium Y 90 anti-CEA monoclonal antibody cT84.66
- Otro: mass spectrometry
Descripción detallada
OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and associated toxicities of concurrent hepatic arterial infusion (HAI) fluorodeoxypyrimidine (FUdR)/Decadron and intravenous gemcitabine combined with intravenous yttrium-90 (^90Y) chimeric T84.66 (cT84.66) in colorectal cancer patients after hepatic resection or maximum surgical debulking (to < 3 cm) of liver metastases.
II. To study the feasibility and toxicities of such adjuvant therapy following resection and/or ablation of liver metastases.
III. To evaluate the biodistribution, clearance and metabolism of ^90Y and ^111In (indium-iii) chimeric T84.66 administered intravenously.
IV. To estimate radiation doses to whole body, normal organs, and tumor through serial nuclear imaging.
V. To correlate proteomic profiles pre and post-therapy with toxicities and anti-tumor effects.
OUTLINE: This is a phase I, dose-escalation study of floxuridine followed by a phase II study.
Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV over 25 minutes on day 9. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Patients may receive an additional course of floxuridine in combination with systemic therapy at the discretion of the treating physician.
After completion of study treatment, patients are followed up at 3 and 6 months.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
California
-
Duarte, California, Estados Unidos, 91010
- City of Hope
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion
- Patients must have a Karnofsky performance status of >= 60%; this must be met pre-surgery and pre-study therapy
- Patients must have histological confirmation of colorectal carcinoma and present with potentially resectable or abatable metachronous or synchronous hepatic metastases
- Patients must have colorectal tumors that produce CEA as documented by either immunohistochemistry or by an elevated serum CEA
- Prior radiotherapy, immunotherapy, or chemotherapy must have been completed at least four weeks prior to start of FUdR/RIT therapy on this study (6 weeks if mitomycin-C or nitrosoureas were part of last therapy) and patients must have recovered from all expected side effects of the prior therapy
- Laboratory values must be met pre-surgery and pre-study therapy
- Hemoglobin > 10 gm % (patients may be transfused to reach a hemoglobin > 10 gm %)
- WBC > 4000/ul
- Absolute granulocyte count of > 1,500/mm^3
- Platelets > 150,000/ul
- Patients may have history of prior malignancy for which the patient has been disease-free for five years with the exception of basal or squamous cell skin cancers or carcinoma in situ of the cervix
- Patients must have no prior history of radiation therapy to the liver
- Total bilirubin < 1.5 (unless reversibly obstructed due to the metastatic tumor)
- Serum creatinine of < 2.0
- Patients must have evidence of intrahepatic metastases involving < 60% of the functioning liver
- Patients cannot have evidence of extrahepatic disease with the following exceptions: patients known to have a resectable "anastomotic" or local recurrence of their tumor; patients who undergoing their initial surgery for resection of their primary colorectal carcinoma can have potentially resectable porta hepatis and/or mesenteric lymph node involvement in addition to liver metastases; patients who have disease extension from the liver metastasis that can be resected en bloc (e.g., diaphragm, kidney, and abdominal wall); patients who have minimal, potentially resectable to less than 3 cm extrahepatic disease
- The pre-operative eligibility checklist must be completed
- If a patient has previously received murine or chimeric antibody, then serum anti-antibody testing must be negative (This must be met pre-surgery if possible)
- Serum HIV testing and hepatitis B surface antigen and C antibody testing must be negative
- Women of childbearing potential must have a negative serum pregnancy test prior to entry and while on study must be practicing an effective form of contraception (This must be met pre-surgery and pre-study therapy)
- Patients must have resectable or abatable liver metastases as determined by the attending surgeon
- Colorectal carcinoma must be confined to the liver except as noted above
- Patients with limited extrahepatic disease as defined (primary, lymph node, or anastomotic recurrence) must have disease resected or debulked to less than 3 cm in greatest dimension
- To receive study therapy, patients must be at least 3 weeks post-surgery but no more than 16 weeks post surgery and without evidence of post-operative complications, such as infection or poor wound healing
- Patients must have < 40% liver resected at the close of completion of the hepatic resection
Exclusion
- Patients that have received radiation therapy to greater than 50% of their bone marrow
- Patients with any nonmalignant intercurrent illness (example cardiovascular, pulmonary, or central nervous system disease) which is either poorly controlled with currently available treatment or which is of such severity that the investigators deem it unwise to enter the patient on protocol shall be ineligible
- Biopsy-proven chronic active hepatitis
Plan de estudios
¿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: Arm I
Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV over 25 minutes on day 9. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may receive an additional course of floxuridine in combination with systemic therapy at the discretion of the treating physician. |
Correlative studies Correlative studies
Otros nombres:
Given IV
Otros nombres:
Given via hepatic arterial infusion
Otros nombres:
Correlative studies Correlative studies
Otros nombres:
Correlative studies
Otros nombres:
Given IV Correlative studies |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Number of Participants With at Least One Dose Limiting Toxicity
Periodo de tiempo: 4 weeks from start of treatment, up to 2 years.
|
Dose Limiting Toxicity (DLT) defined as any treatment-related grade grade 3 nonhematologic toxicity not reversible to grade 2 or less within 24 hours, or any grade 4 toxicity.Up to three cycles of therapy were allowed with DLTs determined based on first cycle tolerance. Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2.0. |
4 weeks from start of treatment, up to 2 years.
|
|
Recommended Phase II Dose
Periodo de tiempo: 4 weeks from start of treatment, up to 2 years.
|
The maximum tolerated dose (MTD) of HAI FUdR in combination with intravenous gemcitabine and 90Y-DTPA-cT84.66 is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design. |
4 weeks from start of treatment, up to 2 years.
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Overall Survival
Periodo de tiempo: Up to 5 years
|
Estimated using the product-limit method of Kaplan and Meier. Event defined as death due to any cause. |
Up to 5 years
|
|
Progression-free Survival
Periodo de tiempo: Up to 5 years
|
Estimated using the product-limit method of Kaplan and Meier. Progression is defined as a 25% increase in the sum of products of measurable lesions over the smallest sum observed, or appearance of any lesions that had disappeared, or appearance of any new lesion/site. |
Up to 5 years
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Jeffrey Wong, City of Hope Medical Center
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 (Estimado)
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
- Enfermedades intestinales
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Neoplasias colorrectales
- Neoplasias Intestinales
- Enfermedades Rectales
- Enfermedades del Colon
- Neoplasias Rectales
- Neoplasias colónicas
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Técnicas de investigación
- Ácidos nucleicos, nucleótidos y nucleósidos
- Desoxicitidina
- Citidina
- Nucleósidos de pirimidina
- Pirimidinas
- Técnicas de química, analítica
- Nucleósidos
- Desoxirribonucleósidos
- Desoxiuridina
- Uridina
- Cromatografía
- Gemcitabina
- Floxuridina
- Espectrometría de Masas
- Chromatography, Liquid
Otros números de identificación del estudio
- 04122
- NCI-2010-01229
- CDR0000590335 (Identificador de registro: PDQ)
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