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Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer

19 de junio de 2013 actualizado por: National Cancer Institute (NCI)

A Phase I/II Trial of Vaccination With Mutant Ras Peptide-Pulsed Dendritic Cells in the Treatment of HLA A2.1 Positive Patients With Colorectal Cancer

RATIONALE: Vaccines may make the body build an immune response that will kill cancer cells. Combining vaccine therapy with interleukin-2 may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy with or without interleukin-2 in treating patients who have locally advanced or metastatic colorectal cancer.

Descripción general del estudio

Descripción detallada

OBJECTIVES:

  • Determine the frequency of immunologic response in patients with locally advanced or metastatic colorectal cancer treated with ras peptide-pulsed dendritic cell vaccine with or without interleukin-2.
  • Determine the tumor response and survival time in patients with metastatic colorectal cancer treated with vaccine plus interleukin-2.
  • Determine the time to progression in patients with locally advanced colorectal cancer treated with adjuvant vaccine.

OUTLINE: Patients are assigned to 1 of 2 treatment groups according to extent of disease. Patients with prior locally advanced disease are assigned to treatment group A, while those with metastatic disease are assigned to treatment group B.

  • Group A: Patients are vaccinated against influenza on day -6. Patients undergo collection of peripheral blood mononuclear cells (PBMC) on day -4. The PBMC are cultured with sargramostim (GM-CSF) and interleukin-4 for 5 days and CD40 ligand for 24 hours and then pulsed for 2 hours with the appropriate peptide to form a vaccine. Patients receive ras peptide-pulsed dendritic cell vaccine IV over 5 minutes on days 1, 15, 29, 43, and 57.
  • Group B: Patients undergo collection of PBMC and receive vaccination as in group A. Patients also receive interleukin-2 subcutaneously on days 2-6 and 9-13.

Treatment in both groups repeats every 2 weeks for up to 5 vaccinations in the absence of disease progression or unacceptable toxicity.

Patients are followed on days 75, 90, 120, and 365.

PROJECTED ACCRUAL: A total of 500 patients will be accrued for this study within 3 years.

Tipo de estudio

Intervencionista

Fase

  • Fase 2
  • Fase 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

    • Maryland
      • Bethesda, Maryland, Estados Unidos, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37232-6838
        • Vanderbilt-Ingram 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

Todos

Descripción

DISEASE CHARACTERISTICS:

  • Histologically confirmed locally advanced or metastatic colorectal cancer
  • Metastatic disease must be radiologically proven
  • HLA-A2-1 positive
  • Locally advanced disease must have had prior resection or incomplete resection with poor prognosis
  • Locally advanced disease includes:

    • Stage III or IV colon cancer (T4 or any T, N2-3, M0)
    • Stage III or IV rectal cancer (T4 or T3, N1-3)
    • Resectable or unresectable T4 disease after radiotherapy, chemotherapy, and/or surgery
    • Absence of measurable disease but more than a 50% chance of recurrence
  • Completely resected or locally advanced disease may have had conventional therapy completed within 1-12 months (surgery alone, with or without adjuvant chemotherapy and/or radiotherapy) prior to study entry
  • Metastatic disease patients must have bidimensionally measurable disease

    • Bone lesions with well-demarcated borders allowed
    • Lesions seen only on bone scan, pleural effusions, ascites, and changes in carcinoembryonic antigen are not considered measurable disease

PATIENT CHARACTERISTICS:

Age:

  • Over 18

Performance status:

  • ECOG 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • Lymphocyte count at least 470/mm^3
  • Granulocyte count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL*
  • SGOT no greater than 4 times upper limit of normal (ULN) (2.5 times ULN for adjuvant patients)*
  • Albumin at least 3 g/dL
  • No active viral hepatitis
  • No evidence of chronic infection due to hepatitis C
  • Hepatitis B surface antigen negative NOTE: *Unless due to metastatic disease

Renal:

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular:

  • No history of cardiac failure, significant arrhythmias, or coronary artery disease (metastatic disease patients only)

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • HIV negative
  • No prior malignancy with a 50% chance of recurrence within 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
  • No medical or psychiatric condition that would preclude compliance
  • No serious medical condition that would preclude apheresis
  • No serious infection
  • No uncontrolled thyroid disease (metastatic disease patients only)
  • Patients with an allergy to eggs are allowed but are not vaccinated against influenza during study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior immunologic therapy directed at the cellular immune system

Chemotherapy:

  • See Disease Characteristics
  • Prior chemotherapy for metastatic disease allowed
  • At least 4 weeks since prior chemotherapy
  • No concurrent chemotherapy or anticipated need for chemotherapy for 2 months after vaccinations

Endocrine therapy:

  • At least 4 weeks since prior supraphysiologic steroid therapy

Radiotherapy:

  • See Disease Characteristics
  • Prior radiotherapy for metastatic disease allowed
  • No concurrent radiotherapy

Surgery:

  • See Disease Characteristics
  • Prior surgery for metastatic disease allowed

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

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Response rate every 3 months for up to a year after completion of study treatment

Colaboradores e Investigadores

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

Investigadores

  • Silla de estudio: John E. Janik, MD, NCI - Metabolism Branch;MET

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

1 de marzo de 1999

Finalización del estudio (Actual)

1 de noviembre de 2005

Fechas de registro del estudio

Enviado por primera vez

11 de julio de 2001

Primero enviado que cumplió con los criterios de control de calidad

26 de enero de 2003

Publicado por primera vez (Estimar)

27 de enero de 2003

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

20 de junio de 2013

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

19 de junio de 2013

Última verificación

1 de noviembre de 2005

Más información

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. .

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