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

NCT00824785 | Terminated Phase 3 DMC

• 1 other identifier: CCR3024
• Study Type: interventional
• Target: 574
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Oesophago-gastric Cancer

Keywords

epirubicin; oxaliplatin; capecitabine; panitumumab

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Study closed early due to lack of efficacy

  Early termination

Secondary Outcomes (1)

• response rate, toxicity, quality of life and PFS

  Early termination

Study Arms (2)

Arm A EOX

ACTIVE COMPARATOR

EOX chemotherapy (epirubicin, oxaliplatin and capecitabine)

Drug: epirubicin, oxaliplatin, capecitabine (EOX)

Arm B EOX + panitumumab.

ACTIVE COMPARATOR

EOX chemotherapy with the addition of panitumumab 9mg/kg every 21 days

Drug: EOX + panitumumab

Interventions

epirubicin, oxaliplatin, capecitabine (EOX) DRUG

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

Arm A EOX

EOX + panitumumab DRUG

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

Arm B EOX + panitumumab.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead

Study Sites (7)

Bournemouth

Bournemouth, United Kingdom

Location

St Luke's Guildford

Guildford, United Kingdom

Location

Royal Liverpool

Liverpool, United Kingdom

Location

Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Clatterbridge Oncology Centre

Metropolitan Borough of Wirral, United Kingdom

Location

Newcastle

Newcastle, United Kingdom

Location

Royal Marsden NHS Foundation Trust

Sutton, United Kingdom

Location

Related Publications (2)

• Smyth EC, Vlachogiannis G, Hedayat S, Harbery A, Hulkki-Wilson S, Salati M, Kouvelakis K, Fernandez-Mateos J, Cresswell GD, Fontana E, Seidlitz T, Peckitt C, Hahne JC, Lampis A, Begum R, Watkins D, Rao S, Starling N, Waddell T, Okines A, Crosby T, Mansoor W, Wadsley J, Middleton G, Fassan M, Wotherspoon A, Braconi C, Chau I, Vivanco I, Sottoriva A, Stange DE, Cunningham D, Valeri N. EGFR amplification and outcome in a randomised phase III trial of chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers. Gut. 2021 Sep;70(9):1632-1641. doi: 10.1136/gutjnl-2020-322658. Epub 2020 Nov 16.

  PMID: 33199443 DERIVED

• Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):481-9. doi: 10.1016/S1470-2045(13)70096-2. Epub 2013 Apr 15.

  PMID: 23594787 DERIVED

MeSH Terms

Interventions

Epirubicin; Oxaliplatin; Capecitabine; Panitumumab

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Prof Cunningham, David

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head GI & Lymphoma Units

Study Record Dates

• First Submitted: January 16, 2009
• First Posted: January 19, 2009
• Study Start: May 1, 2008
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: December 11, 2012

Record last verified: 2012-12

Locations

GB (7)