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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01123473
• Other study ID #: EORTC-40071
• Secondary ID: EU-210362009-011
• Status: Terminated
• Phase: Phase 2
• First received: May 13, 2010
• Last updated: October 11, 2016
• Start date: December 2010
• Est. completion date: September 2014

Study information

• Verified date: October 2016
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Paul-Ehrlich-InstitutHungary: National Institute of PharmacyPortugal: INFARMED, National Authority of Medicines and Health Products, IP
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: September 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Esophageal Neoplasms
• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• capecitabine

• cisplatin

• epirubicin hydrochloride

• fluorouracil

• lapatinib ditosylate

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Brussels
Belgium	U.Z. Gasthuisberg	Leuven
Germany	Johannes Gutenberg Universitaetskliniken	Mainz
Portugal	I.P.O. Francisco Gentil - Centro De Lisboa	Lisboa

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  Germany,  Portugal, 

References & Publications (1)

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-TPS2

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival			No
Secondary	Response rate			No
Secondary	Overall survival			No
Secondary	Toxicity			Yes
Secondary	Concordance of diagnostic tests			No