Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

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

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.

Aperçu de l'étude

Type d'étude

Interventionnel

Inscription (Réel)

41

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

14 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Progression free survival
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Tumoral response
Délai: 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
Délai: 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
Délai: anticipated 3 years
anticipated 3 years
Toxicity
Délai: anticipated 3 years
anticipated 3 years

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

  • Chaise d'étude: Marta Martin Richard, MD, Grupo Espanol Multidisciplinario del Cancer Digestivo

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 octobre 2008

Achèvement primaire (Réel)

1 octobre 2011

Achèvement de l'étude (Réel)

1 décembre 2011

Dates d'inscription aux études

Première soumission

16 décembre 2010

Première soumission répondant aux critères de contrôle qualité

16 décembre 2010

Première publication (Estimation)

17 décembre 2010

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

9 novembre 2012

Dernière mise à jour soumise répondant aux critères de contrôle qualité

8 novembre 2012

Dernière vérification

1 décembre 2010

Plus d'information

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

S'abonner