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

NCT ID: NCT00824785

Last Updated: 2012-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

574 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-05-31

Study Completion Date

2013-02-28

Brief Summary

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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.

Detailed Description

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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

Conditions

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Oesophago-gastric Cancer

Keywords

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epirubicin oxaliplatin capecitabine panitumumab

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A EOX

EOX chemotherapy (epirubicin, oxaliplatin and capecitabine)

Group Type ACTIVE_COMPARATOR

epirubicin, oxaliplatin, capecitabine (EOX)

Intervention Type 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 B EOX + panitumumab.

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

Group Type ACTIVE_COMPARATOR

EOX + panitumumab

Intervention Type 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

Interventions

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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

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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

* 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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Royal Marsden NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Professor David Cunningham

Head GI & Lymphoma Units

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Prof Cunningham, David

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden NHS Foundation Trust

Locations

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Bournemouth

Bournemouth, , United Kingdom

Site Status

St Luke's Guildford

Guildford, , United Kingdom

Site Status

Royal Liverpool

Liverpool, , United Kingdom

Site Status

Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status

Clatterbridge Oncology Centre

Metropolitan Borough of Wirral, , United Kingdom

Site Status

Newcastle

Newcastle, , United Kingdom

Site Status

Royal Marsden NHS Foundation Trust

Sutton, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type DERIVED
PMID: 33199443 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23594787 (View on PubMed)

Other Identifiers

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CCR3024

Identifier Type: -

Identifier Source: org_study_id