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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


Phase 2
18 Years
75 Years
Open (Enrolling)
Both
Adenocarcinoma of the Gastroesophageal Junction, Gastric Cancer

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Trial Information

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


OBJECTIVES:

Primary

- 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.

Secondary

- 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
toxicity.

- 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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the stomach or the esophagogastric
junction

- Metastatic disease OR not amenable to curative surgery

- Tissue material for HER2 and EGFR assessment must be available

- Positive HER2 status by immunohistochemistry (IHC) OR positive EGFR by either
fluorescence in situ hybridization (FISH) or IHC at time of randomization

- No clinical signs of CNS involvement

PATIENT CHARACTERISTICS:

- WHO performance status 0-1

- WBC > 3 x 10^9/L

- Absolute neutrophil count > 1.5 x 10^9/L

- Platelet count > 100 x 10^9/L

- Hemoglobin > 9 g/dL

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST/ALT ≤ 3 times ULN (≤ 5 times ULN in case of liver metastases)

- Serum creatinine ≤ 2.0 mg/dL

- Creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 1 month after
completion of study therapy

- LVEF normal by MUGA scan or ECHO

- No serious cardiac illness within the past 6 months

- No previous or concurrent malignancies except for adequately treated cone-biopsied
carcinoma in situ of the cervix or basal cell carcinoma of the skin

- Able to swallow and retain oral medication

- No history or evidence of interstitial pneumonitis or pulmonary fibrosis

- No uncontrolled infections or serious illnesses, malabsorption syndrome, or medical
conditions including chronic alcohol abuse, hepatitis, HIV, and/or cirrhosis

- No psychological, familial, sociological, or geographical condition potentially
hampering compliance with the study protocol or follow-up schedule

PRIOR CONCURRENT THERAPY:

- At least 12 months since prior neoadjuvant or adjuvant chemotherapy

- No other investigational drugs from 28 days prior to the first dose of study
treatment until 30 days after the last dose of study treatment

- At least 30 days since prior and no concurrent drugs or herbal constituents known to
be inducers or inhibitors of CYP3A4

- No prior palliative systemic chemotherapy

- No prior EGFR pathway-targeting therapy (e.g., antibodies or tyrosine kinase
inhibitors)

- No concurrent traditional Chinese medicines

- No concurrent non-drug therapies such as radiotherapy (other than for pain relief) or
surgery

- No other concurrent anticancer therapy or investigational agents

- No concurrent grapefruit or its juice

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Safety Issue:

No

Principal Investigator

Arnaud Roth, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hopital Cantonal Universitaire de Geneve

Authority:

Unspecified

Study ID:

CDR0000672657

NCT ID:

NCT01123473

Start Date:

December 2010

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Cancer
  • adenocarcinoma of the gastroesophageal junction
  • adenocarcinoma of the stomach
  • stage IIIA gastric cancer
  • stage IIIB gastric cancer
  • stage IIIC gastric cancer
  • stage IV gastric cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Stomach Neoplasms

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