REAL3 Trial of Efficacy of EOX With/Without Panitumumab in Previously Untreated Adv OG Cancer

This study has been terminated.
(Lack of efficacy)
Sponsor:
Information provided by (Responsible Party):
Professor David Cunningham, Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00824785
First received: January 16, 2009
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

To determine whether adding panitumumab, an antibody against the epidermal growth factor receptor (EGFR), to standard chemotherapy with epirubicin, oxaliplatin and capecitabine (EOX), improves the duration of survival of patients with advanced stomach and oesophageal cancer.


Condition Intervention Phase
Oesophago-gastric Cancer
Drug: epirubicin, oxaliplatin, capecitabine (EOX)
Drug: EOX + panitumumab
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: REAL 3 : A Randomised Open-labelled Multicentre Trial of the Efficacy of Epirubicin, Oxaliplatin and Capecitabine (EOX) With or Without Panitumumab in Previously Untreated Advanced Oesophago-gastric Cancer

Resource links provided by NLM:


Further study details as provided by Royal Marsden NHS Foundation Trust:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Early termination ] [ Designated as safety issue: No ]
    Study closed early due to lack of efficacy


Secondary Outcome Measures:
  • response rate, toxicity, quality of life and PFS [ Time Frame: Early termination ] [ Designated as safety issue: No ]
    Study closed early due to lack of efficacy


Enrollment: 574
Study Start Date: May 2008
Estimated Study Completion Date: February 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A EOX
EOX chemotherapy (epirubicin, oxaliplatin and capecitabine)
Drug: epirubicin, oxaliplatin, capecitabine (EOX)
epirubicin 50mg/m(2) IV on day 1 oxaliplatin 130mg/m(2) IV on day 1 with hydration capecitabine 1250mg/m(2)/day PO in two divided doses continuously from days 1-21
Active Comparator: Arm B EOX + panitumumab.
EOX chemotherapy with the addition of panitumumab 9mg/kg every 21 days
Drug: EOX + panitumumab
epirubicin 50mg/m(2) IV on day 1 oxaliplatin 100mg/m(2) IV on day 1 with hydration capecitabine 1000mg/m(2)/day PO in two divided doses continuously from days 1-21 panitumumab -9 mg/kg every 21 days

Detailed Description:

Multicentre phase III, open labelled, randomised controlled trial. Randomisation will be 1:1 Arm A EOX and Arm B EOX + panitumumab. There will be a pilot phase II study of which the first 200 patients will be randomised and the primary endpoint for interim analysis will be when these patients have completed 6 months follow-up

  Eligibility

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

Inclusion Criteria:

  • Histologically verified inoperable locally advanced or metastatic adenocarcinoma or undifferentiated carcinoma of the oesophagus, oesophago-gastric junction, or stomach.
  • Slides of tumour tissue should be available for centralised EGFR staining
  • Uni-dimensionally measurable disease (CT or MRI as per RECIST).
  • No prior chemotherapy including previous adjuvant chemotherapy
  • No prior radiotherapy including adjuvant radiotherapy. Patients receiving palliative radiotherapy to sites of disease that are not measurable may be eligible and should be discussed with the Chief Investigator.
  • Male/female patients aged ≥18 years.
  • WHO Performance status 0, 1 or 2.
  • Patients should have a projected life expectancy of at least 3 months.
  • Completion of baseline quality of life questionnaire (EORTC QLQ C30).
  • Adequate cardiac function; formal measurement of left ventricular ejection fraction is only required if clinically indicated.
  • Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5x109/l; white blood cell count ≥ 3x109/l; platelets ≥ 100x109/l; haemoglobin (Hb) ≥ 9g/dl (can be post-transfusion).
  • Adequate renal function: calculated creatinine clearance ≥50ml/minute.
  • Adequate liver function: serum bilirubin ≤1.5x ULN; ALT/AST ≤2.5x ULN; ALP ≤3x ULN (in the absence of liver metastases). If liver metastases are present, serum transaminases ≤5x ULN are permitted.
  • Written informed consent must be obtained from the patient before any study-specific procedures are performed (see Section 12.0).

Note: Epidermal growth factor receptor (EGFR) positivity by immunohistochemistry will not be required for study entry. Slides obtained from previously collected paraffin embedded archived specimens will be collected centrally for EGFR staining. A multivariate analysis will then be performed to exclude any effects of EGFR status on outcome measures

Exclusion Criteria:

  • Tumours of squamous histology.
  • Patients with locally advanced oesophageal cancer suitable for definitive chemoradiotherapy.
  • Documented or symptomatic brain metastases and/or central nervous system metastases or leptomeningeal disease.
  • Previous chemotherapy or radiotherapy. See Inclusion criteria for note regarding palliative radiotherapy.
  • Any major surgery within 4 weeks prior to the start of study treatment.
  • Any prior treatment with an EGFR signal transduction directed therapy.
  • Treatment with non-permitted medication.
  • Clinically significant (i.e. active) cardiac disease e.g. symptomatic coronary artery disease, uncontrolled cardiac dysrhythmia, or myocardial infarction within the last 12 months. Patients with any history of clinically significant cardiac failure are excluded from study entry.
  • History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan.
  • Known peripheral neuropathy >Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible).
  • Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication (administration of capecitabine by naso-gastric or jejunostomy feeding tube is permitted).
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency.
  • Known hypersensitivity to panitumumab, components of the EOX regimen, or any of the constituents of these agents.
  • Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection.
  • Other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial.
  • Female patients who may be pregnant or breastfeeding. Potential female patients of childbearing potential must have a negative pregnancy test within 7 days prior to randomisation, or have had amenorrhea for more than 2 years.
  • Patients of child-bearing potential not consenting to use adequate contraceptive precautions or abstinence during the course of the study and for 6 months after the last study drug administration for females, and 1 month for males.
  • Any other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
  • Treatment with another investigational agent within 30 days of commencing study treatment.
  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: NCT00824785

Locations
United Kingdom
Bournemouth
Bournemouth, United Kingdom
St Luke's Guildford
Guildford, United Kingdom
Royal Liverpool
Liverpool, United Kingdom
Royal Marsden NHS Foundation Trust
London, United Kingdom, SW3 6JJ
Newcastle
Newcastle, United Kingdom
Royal Marsden NHS Foundation Trust
Sutton, United Kingdom
Clatterbridge Oncology Centre
Wirral, United Kingdom
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
Investigators
Principal Investigator: Prof Cunningham, David Royal Marsden NHS Foundation Trust
  More Information

No publications provided by Royal Marsden NHS Foundation Trust

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Professor David Cunningham, Head GI & Lymphoma Units, Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00824785     History of Changes
Other Study ID Numbers: CCR3024
Study First Received: January 16, 2009
Last Updated: December 10, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Royal Marsden NHS Foundation Trust:
epirubicin
oxaliplatin
capecitabine
panitumumab

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Epirubicin
Oxaliplatin
Capecitabine
Fluorouracil
Antibodies, Monoclonal
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2014