Study of Oxaliplatin and Sorafenib Combination to Treat Gastric Cancer Relapsed After a Cisplatin Based Treatment
|ClinicalTrials.gov Identifier: NCT01262482|
Recruitment Status : Completed
First Posted : December 17, 2010
Last Update Posted : November 9, 2012
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 or disease||Intervention/treatment||Phase|
|Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (Relapsed After a Cisplatin Based Treatment)||Drug: Oxaliplatin Drug: Sorafenib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||October 2008|
|Actual Primary Completion Date :||October 2011|
|Actual Study Completion Date :||December 2011|
|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.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.
- Progression free survival [ Time Frame: anticipated 3 years ]Measurements according to RECIST criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan and Magnetic Resonance Imaging (MRI)
- Tumoral response [ Time Frame: anticipated 3 years ]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 ]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 ]
- Toxicity [ Time Frame: anticipated 3 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01262482
|Hospital Clinic de Barcelona|
|Hospital Sant Pau|
|H. Josep Trueta|
|Centro Oncológico M.D. Anderson Spain|
|Hospital de Fuenlabrada|
|Hospital La Paz|
|Clínica Universitaria de Navarra|
|Hospital Parc Taulí|
|Hospital General de Valencia|
|Study Chair:||Marta Martin Richard, MD||Grupo Espanol Multidisciplinario del Cancer Digestivo|