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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grupo Espanol Multidisciplinario del Cancer Digestivo
ClinicalTrials.gov Identifier:
NCT01262482
First received: December 16, 2010
Last updated: November 8, 2012
Last verified: December 2010
  Purpose

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.


Condition Intervention Phase
Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (Relapsed After a Cisplatin Based Treatment)
Drug: Oxaliplatin
Drug: Sorafenib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Grupo Espanol Multidisciplinario del Cancer Digestivo:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: anticipated 3 years ] [ Designated as safety issue: No ]
    Measurements according to RECIST criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan and Magnetic Resonance Imaging (MRI)


Secondary Outcome Measures:
  • Tumoral response [ Time Frame: anticipated 3 years ] [ Designated as safety issue: No ]
    Measurements according to RECIST criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan and Magnetic Resonance Imaging (MRI)

  • Response duration [ Time Frame: anticipated 3 years ] [ Designated as safety issue: No ]
    Duration of the partial or total response to the treatment. Evaluation and classification according to RECIST criteria (Response Evaluation Criteria in Solid Tumors)

  • Overall survival [ Time Frame: anticipated 3 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: anticipated 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 41
Study Start Date: October 2008
Study Completion Date: December 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oxaliplatin + Sorafenib Drug: Oxaliplatin
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.
Drug: Sorafenib
400mg, orally, 2 times per day. Until progression, intolerance or unacceptable toxicity develops, or until patient or investigator decide to stop the treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01262482

Locations
Spain
Hospital Sant Pau
Barcelona, Spain
Hospital Clinic de Barcelona
Barcelona, Spain
H. Josep Trueta
Girona, Spain
Hospital La Paz
Madrid, Spain
Centro Oncológico M.D. Anderson Spain
Madrid, Spain
Hospital de Fuenlabrada
Madrid, Spain
Hospital Althaia
Manresa, Spain
Clínica Universitaria de Navarra
Pamplona, Spain
Hospital Parc Taulí
Sabadell, Spain
Hospital General de Valencia
Valencia, Spain
Sponsors and Collaborators
Grupo Espanol Multidisciplinario del Cancer Digestivo
Investigators
Study Chair: Marta Martin Richard, MD Grupo Espanol Multidisciplinario del Cancer Digestivo
  More Information

No publications provided

Responsible Party: Grupo Espanol Multidisciplinario del Cancer Digestivo
ClinicalTrials.gov Identifier: NCT01262482     History of Changes
Other Study ID Numbers: GEMCAD-0802, 2008-004223-27
Study First Received: December 16, 2010
Last Updated: November 8, 2012
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica

Keywords provided by Grupo Espanol Multidisciplinario del Cancer Digestivo:
adenocarcinoma
gastric
gastroesophageal junction
Relapsed
sorafenib
oxaliplatin

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Oxaliplatin
Sorafenib
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014