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Study of Oxaliplatin and Sorafenib Combination to Treat Gastric Cancer Relapsed After a Cisplatin Based Treatment

8 de noviembre de 2012 actualizado por: Grupo Espanol Multidisciplinario del Cancer Digestivo

A Phase 2 Trial of Oxaliplatin and Sorafenib Combination in Patients With Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma, Relapsed After a Cisplatin Based Treatment

In Spain, the gastric carcinoma is the 5th most frequent malignant tumor in women and the 6th in men, and represents the 3rd cause of cancer-related deaths amongst women and the 4th amongst men. The average of 5-year survival rate in Spain is under 30%. The main reason of it is that, despite carrying out an adjuvant treatment, more than the 50% will present relapsed disease.

Sorafenib has been the first RAF inhibitor, both of RAF-1 and B-rRAF and its b-RAF variant V600E. Moreover, it has shown its ability to inhibit other tyrosin-quinase receptors as VEGFR 2 and 3, c-kit, Flt-3 or PDGFR. Its activity has been clearly proven in clear cell renal carcinoma.

The mechanism by which Sorafenib seems to act is not because of the existence of a mutation of RAS or RAF, but because as there is a VHL shortage the HIP produces a VEGF, bFGF or TGF overexpression that produces in turn a hyper-stimulation on the RAF/ERK/MEK pathway.

The RAF/MEK/ERK pathway and angiogenesis seem to be clearly involved in the gastric carcinoma tumorigenesis and progression. Because of that, it seems interesting to associate Sorafenib to an oxaliplatin-based chemotherapy, which has shown its effectiveness in relapsed patients after receiving cisplatin-based schemes. Moreover, there is a phase 1 trial confirming the tolerance of the oxaliplatin and Sorafenib association, describing partial responses amongst gastric cancer patients previously treated with cisplatin.

Descripción general del estudio

Tipo de estudio

Intervencionista

Inscripción (Actual)

41

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

      • Barcelona, España
        • Hospital Clinic de Barcelona
      • Barcelona, España
        • Hospital Sant Pau
      • Girona, España
        • H. Josep Trueta
      • Madrid, España
        • Hospital La Paz
      • Madrid, España
        • Hospital De Fuenlabrada
      • Madrid, España
        • Centro Oncológico M.D. Anderson Spain
      • Manresa, España
        • Hospital Althaia
      • Pamplona, España
        • Clinica Universitaria de Navarra
      • Sabadell, España
        • Hospital Parc Tauli
      • Valencia, España
        • Hospital General de Valencia

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

14 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  1. Gastric or gastroesophageal junction adenocarcinoma confirmed by cytology or biopsy, with unresectable or metastatic disease which have progressed to a cisplatin-fluoropyrimidine based scheme (excluded neoadjuvant treatment administered with or without concomitant radiotherapy)
  2. Older than 18 years at the moment of informed consent form signature
  3. Age > 18 years
  4. ECOG 0-2
  5. Measurable disease by RECIST criteria. Lesions have to be measured by CT-scan or MRI
  6. Life expectancy > 12 weeks
  7. Adequate medullary reserve and hepatic and renal function, defined according to the following parameters:

    1. Hemoglobin ≥ 9g/dl
    2. Neutrophils ≥ 1,5 x 10^9/L
    3. Platelets ≥100 x 10^9/L
    4. Total bilirubin ≤ 1,5 times the upper limit of normal (ULN)
    5. ALT (GTP) and AST (GOT) ≤ 2,5 times the upper limit of normal (ULN) (≤ 5 times the ULN in patients with hepatic metastasis)
    6. PT-INR-PTT ≤ 1,5 times the ULN. (The patients under anticoagulant treatment with dicumarin or heparin can be included if there is no previous evidence of alteration in these parameters)
    7. Creatinine clearance > 30ml/min
  8. The patients have to be able to understand the meaning of their participation in the trial and voluntary give their participation consent signing the informed consent form

Exclusion Criteria:

  1. More than one line for the treatment of locally advanced disease
  2. Active ischemic cardiopathy. History of cardiac disease defined as follow:

    1. Congestive cardiac failure > class 2 from the NYHA
    2. Active coronary disease. The recruitment of patients with solved myocardial infarction is allowed, if diagnosed at least 6 months before the trial start
    3. Cardiac arrhythmia requiring treatment with antiarrhythmic drugs. (The treatment with beta-adrenergic antagonists or digoxin is allowed)
    4. Non-controlled arterial hypertension
  3. Non-controlled intercurrent illness
  4. Symptomatic sensitive peripheral neuropathy
  5. Another malignant disease diagnosed in the past 5 years, except in situ cervix carcinoma adequately treated, non-melanoma skin carcinoma, superficial bladder tumor (Ta, Tis and T1), or any tumor treated in a curative way until 3 years prior to the recruitment
  6. Pregnant or breastfeeding women. Women will have to undergo a pregnancy test within 7 days prior to the recruitment. Both men and women recruited in the trial will have to use appropriate barrier contraceptive methods during their sexual relations during the trial period and at least until two weeks after its completion. Men participating in this trial will have to continue using this contraceptive methods at least until 3 months after the treatment completion
  7. Chronic diseases: AIDS, Hepatitis B and/or Hepatitis C
  8. Clinically active severe infection (Grade 2 NCI-CTC version 3.0)
  9. Cerebral metastasis or meningeal tumor
  10. Patients requiring chronic corticosteroid treatment or high doses of corticosteroids or any other immunosuppressive treatment
  11. Patients having undergone a major surgery within the 4 weeks prior to the trial start
  12. Patients having completed a chemotherapy or radiotherapy treatment within the 4 weeks prior to the clinical trial start (except palliative radiotherapy, within the 2-weeks prior to the clinical trial start)
  13. Previous treatment using a RAS pathway inhibitor
  14. Any medical or severe psychiatric condition or drug consumption involving a serious risk for the patient if taking part in the clinical trial or that can prevent the signature of the informed consent form
  15. Patients unable to swallow medication

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: Oxaliplatin + Sorafenib
130 mg/m2, IV during 2 hours on day 1 of each 21 day cycle. Number of cycles: until progression, intolerance or unacceptable toxicity develops, or until patient or investigator decide to stop the treatment.
400mg, orally, 2 times per day. Until progression, intolerance or unacceptable toxicity develops, or until patient or investigator decide to stop the treatment.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Progression free survival
Periodo de tiempo: anticipated 3 years
Measurements according to RECIST criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan and Magnetic Resonance Imaging (MRI)
anticipated 3 years

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Tumoral response
Periodo de tiempo: anticipated 3 years
Measurements according to RECIST criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan and Magnetic Resonance Imaging (MRI)
anticipated 3 years
Response duration
Periodo de tiempo: anticipated 3 years
Duration of the partial or total response to the treatment. Evaluation and classification according to RECIST criteria (Response Evaluation Criteria in Solid Tumors)
anticipated 3 years
Overall survival
Periodo de tiempo: anticipated 3 years
anticipated 3 years
Toxicity
Periodo de tiempo: anticipated 3 years
anticipated 3 years

Colaboradores e Investigadores

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

Investigadores

  • Silla de estudio: Marta Martin Richard, MD, Grupo Espanol Multidisciplinario del Cancer Digestivo

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 octubre de 2008

Finalización primaria (Actual)

1 de octubre de 2011

Finalización del estudio (Actual)

1 de diciembre de 2011

Fechas de registro del estudio

Enviado por primera vez

16 de diciembre de 2010

Primero enviado que cumplió con los criterios de control de calidad

16 de diciembre de 2010

Publicado por primera vez (Estimar)

17 de diciembre de 2010

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

9 de noviembre de 2012

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

8 de noviembre de 2012

Última verificación

1 de diciembre de 2010

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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