Epirubicin Hydrochloride, Cisplatin, and Fluorouracil or Capecitabine With or Without Lapatinib Ditosylate as First-Line Therapy in Treating Patients With Stomach Cancer or Gastroesophageal Junction Cancer

NCT ID: NCT01123473

Last Updated: 2016-10-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2014-09-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as epirubicin hydrochloride, cisplatin, fluorouracil, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving combination chemotherapy together with or without lapatinib ditosylate is more effective in treating patients with cancer of the stomach or gastroesophageal junction.

PURPOSE: This randomized phase II trial is studying how well epirubicin hydrochloride, cisplatin, and fluorouracil or capecitabine works when given together with or without lapatinib ditosylate as first-line therapy in treating patients with stomach cancer or gastroesophageal junction cancer.

Detailed Description

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.

Conditions

Adenocarcinoma of the Gastroesophageal Junction; Gastric Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Lapatinib

Chemotherapy + lapatinib

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

epirubicin hydrochloride

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

lapatinib ditosylate

Intervention Type: DRUG

Placebo

Chemotherapy + placebo

Group Type: PLACEBO_COMPARATOR

capecitabine

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

epirubicin hydrochloride

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

Interventions

capecitabine

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

epirubicin hydrochloride

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

lapatinib ditosylate

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arnaud Roth

Role: STUDY_CHAIR

Hopital Cantonal Universitaire de Geneve

Locations

Institut Jules Bordet

Brussels, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Johannes Gutenberg Universitaetskliniken

Mainz, , Germany

I.P.O. Francisco Gentil - Centro De Lisboa

Lisbon, , Portugal

Countries

Belgium; Germany; Portugal

References

Roth A, Moehler MH, Mauer M, et al.: Lapatinib in combination with ECF/x in EGFR1 or HER2-overexpressing first-line metastatic gastric cancer (GC): A phase II randomized placebo controlled trial (EORTC 40071). [Abstract] J Clin Oncol 28 (Suppl 15): A-TPS205, 2010.

Reference Type: RESULT

Other Identifiers

EU-21036

Identifier Type: -

Identifier Source: secondary_id

2009-011580-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EORTC-40071

Identifier Type: -

Identifier Source: org_study_id