Study of Oxaliplatin and Sorafenib Combination to Treat Gastric Cancer Relapsed After a Cisplatin Based Treatment
Status:
Completed
Trial end date:
2011-12-01
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 2
Details
Lead Sponsor:
Grupo Espanol Multidisciplinario del Cancer Digestivo