Effectiveness of First Line Treatment With Lapatinib and ECF/X in Histologically Proven Adenocarcinoma of the Stomach or the Esophagogastric Junction, Metastatic or Not Amenable to Curative Surgery According to HER2 and EGFR Status: a Randomized Phase II Trial
- To determine the activity of first-line treatment comprising epirubicin hydrochloride,
cisplatin, and fluorouracil or capecitabine with or without lapatinib ditosylate in
patients with adenocarcinoma of the stomach or esophagogastric junction that is
metastatic or not amenable to curative surgery according to HER2 and EGFR status.
- To explore the activity of this regimen in patients who are HER2 negative by FISH, but
HER2 positive by IHC (2+ and 3+) as well as patients who are HER2 positive or negative
by FISH and negative by IHC (0 or 1+), but EGFR positive by FISH or by IHC (2+ and 3+).
- To assess the concordance of HER2 determination by FISH and IHC.
OUTLINE: This is a multicenter study. Patients are stratified according to institution and
the combination of EGFR/HER2 status as determined by fluorescence in situ hybridization
(FISH) and immunohistochemistry (IHC) assays (HER2 positive by FISH/HER2 positive by IHC
2/3+ vs HER2 negative by FISH/HER2 positive by IHC 2/3+ vs HER2 negative by IHC 0/1+/EGFR
positive by FISH or by IHC 2/3+). Patients are randomized to 1 of 2 treatment arms.
- Arm I (experimental): Patients receive epirubicin hydrochloride IV and cisplatin IV on
day 1; fluorouracil IV continuously on days 1-21 or oral capecitabine twice daily on
days 1-21; and oral lapatinib ditosylate once daily on days 1-21. Treatment repeats
every 21 days for 6 courses in the absence of disease progression or unacceptable
- Arm II (control): Patients receive epirubicin hydrochloride, cisplatin, and
fluorouracil or capecitabine as in arm I. Patients also receive oral placebo once daily
on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 8 weeks, every 3 months for 2
years, and then every 6 months thereafter.
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment
Arnaud Roth, MD
Hopital Cantonal Universitaire de Geneve