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

This study has been terminated.
(company withdrew interest)
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT01123473
First received: May 13, 2010
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Gastroesophageal Junction
Gastric Cancer
Drug: capecitabine
Drug: cisplatin
Drug: epirubicin hydrochloride
Drug: fluorouracil
Drug: lapatinib ditosylate
Phase 2

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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Concordance of diagnostic tests [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: December 2010
Estimated Study Completion Date: August 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapatinib
Chemotherapy + lapatinib
Drug: capecitabine Drug: cisplatin Drug: epirubicin hydrochloride Drug: fluorouracil Drug: lapatinib ditosylate
Placebo Comparator: Placebo
Chemotherapy + placebo
Drug: capecitabine Drug: cisplatin Drug: epirubicin hydrochloride Drug: fluorouracil

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01123473

Locations
Belgium
Institut Jules Bordet
Brussels, Belgium
U.Z. Gasthuisberg
Leuven, Belgium
Germany
Johannes Gutenberg Universitaetskliniken
Mainz, Germany
Portugal
I.P.O. Francisco Gentil - Centro De Lisboa
Lisboa, Portugal
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Arnaud Roth Hopital Cantonal Universitaire de Geneve
  More Information

Additional Information:
Publications:
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.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT01123473     History of Changes
Other Study ID Numbers: EORTC-40071, EU-21036, 2009-011580-36
Study First Received: May 13, 2010
Last Updated: July 30, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Hungary: National Institute of Pharmacy
Portugal: INFARMED, National Authority of Medicines and Health Products, IP

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
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

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Capecitabine
Lapatinib
Cisplatin
Epirubicin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites

ClinicalTrials.gov processed this record on August 19, 2014