Erbitux in Combination With Xeloda and Cisplatin in Advanced Esophago-gastric Cancer (EXPAND)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00678535
First received: May 13, 2008
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

The primary objective of this study is to demonstrate that addition of cetuximab to 1st-line treatment with capecitabine (Xeloda, X) and cisplatin (P) [XP] chemotherapy regimen has a clinically relevant benefit for subjects with advanced gastric adenocarcinoma including gastroesophageal junction (GEJ) adenocarcinoma, in terms of progression free survival (PFS).

Secondary objectives are to assess cetuximab plus XP versus XP alone with respect to overall survival, overall tumor response, quality of life (QoL) and safety.


Condition Intervention Phase
Gastric Cancer
Drug: Cetuximab
Drug: Capecitabine
Drug: Cisplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Randomized, Controlled, Multicenter Phase III Study Investigating Cetuximab in Combination With Capecitabine (Xeloda, X) and Cisplatin (P) Versus XP Alone as First-line Treatment for Subjects With Advanced Gastric Adenocarcinoma Including Adenocarcinoma of the Gastroesophageal Junction

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments [ Time Frame: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012) ] [ Designated as safety issue: No ]
    The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause within 60 days of the last tumor assessment or randomization. Participants without event are censored on the date of last tumor assessment.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012) ] [ Designated as safety issue: No ]
    The OS time is defined as the time from randomization to death or last day known to be alive. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.

  • Best Overall Response (BOR) Rate: Independent Review Committee (IRC) Assessments [ Time Frame: Every 6 weeks until progression, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012) ] [ Designated as safety issue: No ]
    The BOR rate is defined as the percentage of participants having achieved complete response (CR) or partial response (PR) as the best overall response, based on radiological assessments (based on response evaluation criteria in solid tumors [RECIST] Version 1.0) from the IRC.

  • Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012) ] [ Designated as safety issue: No ]
    Mean global health status and social functioning scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a better QoL.

  • Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire [ Time Frame: Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012) ] [ Designated as safety issue: No ]
    EQ-5D questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 single items are combined to obtain a single index score that is health utility index (HUI) score reflecting subject's preferences for different health states. The lowest possible score is -0.59 and the highest is 1.00, higher scores on the EQ-5D represent a better QoL.

  • Safety - Number of Participants With Adverse Events (AEs) [ Time Frame: Time from first dose up to Day 30 after last dose of study treatment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012) ] [ Designated as safety issue: Yes ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered.


Enrollment: 904
Study Start Date: June 2008
Study Completion Date: February 2013
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab plus Capecitabine plus Cisplatin Drug: Cetuximab
Single first dose of cetuximab 400 milligram per square meter (mg/m^2) will be administered intravenously over 120 minutes followed by weekly intravenous infusion of cetuximab 250 mg/m^2 over 60 minutes in each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Other Name: Erbitux
Drug: Capecitabine
Capecitabine 1000 mg/m^2 will be administered orally twice daily from evening of Day 1 to morning of Day 15 for every 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Other Name: Xeloda
Drug: Cisplatin
Cisplatin 80 mg/m^2 will be administered intravenously with infusion over 1 to 4 hours on Day 1 of each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Active Comparator: Capecitabine plus Cisplatin Drug: Capecitabine
Capecitabine 1000 mg/m^2 will be administered orally twice daily from evening of Day 1 to morning of Day 15 for every 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Other Name: Xeloda
Drug: Cisplatin
Cisplatin 80 mg/m^2 will be administered intravenously with infusion over 1 to 4 hours on Day 1 of each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent before any study-related activities are carried out
  • Age greater than or equal to (>=) 18 years
  • Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Adenocarcinoma of the gastroesophageal junction [AEG] Types I-III according to Siewert classification)
  • Archived tumor material sample for at least subsequent standardized Epidermal Growth Factor Receptor (EGFR) expression assessment
  • Unresectable advanced (M0) or unresectable metastatic (M1) disease
  • At least one radiographically documented measurable lesion in a previously non-irradiated area according to response evaluation criteria in solid tumors (RECIST). The primary tumor site is to be considered as a non-measurable lesion only
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Estimated life expectancy greater than (>) 12 weeks
  • Medically accepted contraception (if the risk of conception exists)
  • Glomerular filtration rate (GFR) >= 60 milliliter per minute (mL/min) The GFR is based on the Cockcroft-Gault formula for creatinine clearance
  • Aspartate-aminotransferase (ASAT) less than or equal to (=<) 2.5 * upper limit of normal (ULN) and alanine-aminotransferase (ALAT) =< 2.5 *ULN
  • Bilirubin =< 3 * ULN
  • Absolute neutrophil count (ANC) >= 1.5 * 10^9 per liter
  • Platelets >= 100 * 10^9 per liter
  • Hemoglobin >=10 gram per deciliter (g/dL) (without transfusions)
  • Sodium and potassium within normal limits or =< 10 percent above or below (supplementation permitted)

Exclusion Criteria:

  • Prior chemotherapy, however, previous (neo-)adjuvant (radio-) chemotherapy allowed if finished > 1 year prior to start of study treatment and no more than 300 mg/m^2 cisplatin has been administered
  • Prior treatment with an antibody or molecule targeting EGFR and/or Vascular Endothelial Growth Factor Receptor (VEGFR) related signaling pathways
  • Brain metastasis and/or leptomeningeal disease (known or suspected)
  • Radiotherapy (except localized radiotherapy for pain relief), major surgery or any investigational drug within 30 days before the start of study treatment
  • Concurrent chronic systemic immune or hormone therapy not indicated in this study protocol (except for physiologic replacement)
  • Clinically relevant coronary artery disease (New York Heart Association [NYHA] functional angina classification III/IV), congestive heart failure (NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the 12 months before study Screening, or high risk of uncontrolled arrhythmia
  • Active Hepatitis B or C
  • Chronic diarrhea or short bowel syndrome
  • Presence of any contra-indication to treatment with cetuximab, capecitabine and cisplatin including:

    • Known hypersensitivity to capecitabine, fluorouracil, cisplatin, cetuximab or to any of the excipients of these drugs
    • Known dihydropyrimidine dehydrogenase (DPD) deficiency
    • Hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
    • Current treatment with sorivudine or chemically related analogues, such as brivudine
    • Symptomatic peripheral neuropathy National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >= 2 and/or ototoxicity NCI CTCAE Grade >= 2, except if due to trauma or mechanical impairment due to tumor mass
  • Pregnancy or lactation period
  • Concurrent treatment with a non-permitted drug
  • Treatment in another clinical study within 30 days prior to study screening
  • Previous malignancy other than gastric cancer within 5 years prior to study screening, except for basal cell cancer of the skin or pre-invasive cancer of the cervix
  • Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent
  • Legal incapacity or limited legal capacity
  • Significant disease which, in the Investigator's opinion, would exclude the subject from the study
  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: NCT00678535

  Show 130 Study Locations
Sponsors and Collaborators
Merck KGaA
Investigators
Principal Investigator: Florian Lordick, MD, PhD University Clinic Leipzig, University Cancer Center Leipzig (UCCL), Leipzig Germany
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00678535     History of Changes
Other Study ID Numbers: EMR 200048-052, 2007-004219-75
Study First Received: May 13, 2008
Results First Received: March 30, 2013
Last Updated: July 11, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Austria: Austrian Medicines and Medical Devices Agency
Austria: Ethikkommission
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Ethics Committee
Brazil: National Committee of Ethics in Research
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ethics committee
Chile: Comité de Ética Científico
Chile: Comisión Nacional de Investigación Científica y Tecnológica
China: Food and Drug Administration
China: Ethics Committee
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Paul-Ehrlich-Institut
Greece: Ethics Committee
Greece: National Organization of Medicines
Hong Kong: Ethics Committee
Israel: Ethics Commission
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: Ethics Committee
Japan: Foundation for Biomedical Research and Innovation
Japan: Institutional Review Board
Korea: Food and Drug Administration
Korea: Institutional Review Board
Poland: Ministry of Science and Higher Education
Poland: National Institute of Medicines
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: Ethics Committee for Clinical Research
Portugal: Health Ethic Committee
Portugal: National Pharmacy and Medicines Institute
Romania: Ethics Committee
Romania: Ministry of Public Health
Romania: National Agency for Medicines and Medical Devices
Romania: National Authority for Scientific Research
Russia: Ethics Committee
Russia: Pharmacological Committee, Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica
Taiwan : Food and Drug Administration
Taiwan: Institutional Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Councils UK

Keywords provided by Merck KGaA:
1st line treatment for Gastric Cancer
Cetuximab
Capecitabine
Xeloda
Cisplatin
Progression-free survival

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Capecitabine
Cetuximab
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014