Chemotherapy With or Without Bevacizumab or Lapatinib to Treat Operable Oesophagogastric Cancer
NCT ID: NCT00450203
Last Updated: 2016-12-01
Study Results
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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UNKNOWN
PHASE2/PHASE3
1103 participants
INTERVENTIONAL
2007-10-31
2017-12-31
Brief Summary
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PURPOSE: This randomized phase II/III trial is studying the side effects and how well giving combination chemotherapy together with bevacizumab works compared with combination chemotherapy alone in treating patients with previously untreated stomach cancer, gastroesophageal junction cancer or lower oesophageal cancer that can be removed by surgery. The feasibility study is studying the safety of adding lapatinib to chemotherapy in patients with HER-2 positive previously untreated stomach cancer, gastroesophageal junction cancer or lower oesophageal cancer that can be removed by surgery. The feasibility study will also assess the feasibility of timely HER-2 testing and estimate the HER-2 positivity rate in this patient population.
Detailed Description
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Primary
* Assess the safety and efficacy of neoadjuvant and adjuvant chemotherapy comprising epirubicin hydrochloride, cisplatin, and capecitabine with or without bevacizumab in patients with previously untreated, resectable gastric, gastroesophageal junction or lower oesophageal cancer.
* Assess the safety of neoadjuvant and adjuvant chemotherapy comprising epirubicin hydrochloride, cisplatin, and capecitabine with or without lapatinib in patients with HER-2 positive previously untreated, resectable gastric, gastroesophageal junction or lower oesophageal cancer.
OUTLINE: This is a multicenter, randomized, open-label, controlled study. Patients are randomized to 1 of 4 treatment arms.
* Arm I and II: Patients receive epirubicin hydrochloride IV and cisplatin IV over 4 hours on day 1 and capecitabine orally twice daily on days 1-21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo surgery 5-6 weeks after completion of chemotherapy. Patients then receive 3 additional courses of chemotherapy beginning 6-10 weeks after surgery.
* Arm II: Patients receive bevacizumab IV over 30-90 minutes, epirubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1 and capecitabine orally twice daily on days 1-21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo surgery 5-8 weeks after completion of chemotherapy. Patients then receive 3 additional courses of chemotherapy and bevacizumab beginning 6-10 weeks after surgery. Patients then receive maintenance therapy comprising bevacizumab IV over 30-90 minutes on day 1. Maintenance therapy repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm IV: Patients receive lapatinib orally once daily, epirubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1 and capecitabine orally twice daily on days 1-21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo surgery 5-8 weeks after completion of chemotherapy. Patients then receive 3 additional courses of chemotherapy and lapatinib beginning 6-10 weeks after surgery. Patients then receive maintenance therapy comprising lapatinib orally once daily on days 1-21. Maintenance therapy repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, during treatment, and during the follow-up period.
After completion of study treatment, patients are followed at 9, 18, and 27 weeks after the start of course 4, 1 year post surgery, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 1063 patients were recruited to the bevacizumab comparison of the study (now closed to recruitment) and 40 patients with HER-2 positive tumours will be recruited into the ST03 feasibility study.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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ECX + Bevacizumab
ECX + Bevacizumab
bevacizumab
7.5mg/kg IV Day 1 of each 21 cycle of chemotherapy (6 cycles) plus day 1 of each maintenance dose every 21 days for 6 doses.
capecitabine
dose banded as based on patient BSA. Oral dose given twice a day during each 21 day cycle of chemotherapy (6 cycles in total)
cisplatin
60mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
Epirubicin
50mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
adjuvant therapy
3 cycles of ECX chemotherapy post operatively
conventional surgery
Surgery undertaken after 3 cycles of pre-operative chemotherapy. Followed by 3 cycles of chemotherapy.
neoadjuvant therapy
3 cycles of pre-operative ECX chemotherapy.
Epirubicin, Cisplatin and Capecitabine
ECX chemotherapy
capecitabine
dose banded as based on patient BSA. Oral dose given twice a day during each 21 day cycle of chemotherapy (6 cycles in total)
cisplatin
60mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
Epirubicin
50mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
adjuvant therapy
3 cycles of ECX chemotherapy post operatively
conventional surgery
Surgery undertaken after 3 cycles of pre-operative chemotherapy. Followed by 3 cycles of chemotherapy.
neoadjuvant therapy
3 cycles of pre-operative ECX chemotherapy.
ECX + Lapatinib
ECX + Lapatinib
capecitabine
dose banded as based on patient BSA. Oral dose given twice a day during each 21 day cycle of chemotherapy (6 cycles in total)
cisplatin
60mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
Epirubicin
50mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
adjuvant therapy
3 cycles of ECX chemotherapy post operatively
conventional surgery
Surgery undertaken after 3 cycles of pre-operative chemotherapy. Followed by 3 cycles of chemotherapy.
neoadjuvant therapy
3 cycles of pre-operative ECX chemotherapy.
Lapatinib
1250mg/day Day 1-21 of each cycle of chemotherapy (6 cycles) plus day 1-21 of each maintenance course every 21 days for 6 doses.
Interventions
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bevacizumab
7.5mg/kg IV Day 1 of each 21 cycle of chemotherapy (6 cycles) plus day 1 of each maintenance dose every 21 days for 6 doses.
capecitabine
dose banded as based on patient BSA. Oral dose given twice a day during each 21 day cycle of chemotherapy (6 cycles in total)
cisplatin
60mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
Epirubicin
50mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
adjuvant therapy
3 cycles of ECX chemotherapy post operatively
conventional surgery
Surgery undertaken after 3 cycles of pre-operative chemotherapy. Followed by 3 cycles of chemotherapy.
neoadjuvant therapy
3 cycles of pre-operative ECX chemotherapy.
Lapatinib
1250mg/day Day 1-21 of each cycle of chemotherapy (6 cycles) plus day 1-21 of each maintenance course every 21 days for 6 doses.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Previously untreated disease
PATIENT CHARACTERISTICS:
* WHO performance status 0 or 1
* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9 g/dL (can be post transfusion)
* WBC ≥ 3,000/mm\^3
* Glomerular filtration rate ≥ 60 mL/min
* Proteinuria ≤ 1 g by 24-hour urine collection
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* ALT and AST ≤ 2.5 times ULN
* Alkaline phosphatase ≤ 3 times ULN (in the absence of liver metastases)
* INR ≤ 1.5
* PTT ≤ 1.5 times ULN
* FEV\_1 ≥ 1.5 L
* Cardiac ejection fraction ≥ 50% by MUGA scan or echocardiogram
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Must be fit enough to receive protocol treatment
* No other malignancies within the past 5 years except for curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
* No prior or concurrent significant medical conditions, including any of the following:
* Cerebrovascular disease (including transient ischemic attack and stroke) within the past year
* Cardiovascular disease, including the following:
* Myocardial infarction within the past year
* Uncontrolled hypertension while receiving chronic medication
* Unstable angina
* New York Heart Association class II-IV congestive heart failure
* Serious cardiac arrhythmia requiring medication
* Major trauma within the past 28 days
* Serious nonhealing wound, ulcer, or bone fracture
* Evidence of bleeding diathesis or coagulopathy
* Recent history of any active gastrointestinal inflammatory condition (e.g., peptic ulcer disease, diverticulitis, or inflammatory bowel disease)
* If patients have a known diagnosis of any of the above, evidence of disease control is required by negative endoscopy within the past 28 days
* No severe tinnitus
* No lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication
* No known peripheral neuropathy ≥ 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)
* No known dihydropyrimidine dehydrogenase deficiency
* No history of interstitial lung disease or radiological evidence of lung fibrosis
* No known allergy to any of the following:
* Chinese hamster ovary cell proteins
* Other recombinant human or humanized antibodies
* Any excipients of bevacizumab formulation or platinum compounds
* Any other components of the study drugs
Due to an increase in perforations associated with self-expandable metal stents in patients with colorectal cancer receiving bevacizumab, patients with an oesophageal or gastric stent (metal or biodegradable) in situ are ineligible for the study.
PRIOR CONCURRENT THERAPY:
* No prior anthracycline
* More than 28 days since prior major surgery or open biopsy
* More than 10 days since prior thrombolytic therapy
* No concurrent thrombolytic therapy
* No concurrent dipyridamole
* No concurrent capecitabine or sorivudine (or sorivudine analogues \[e.g., brivudine\])
* No chronic, daily high-dose acetylsalicylic acid (\> 325 mg/day) or nonsteroidal anti-inflammatory drugs
* No chronic corticosteroids (≥ 10 mg/day methylprednisolone equivalent)
* Inhaled steroids allowed
* No other concurrent cytotoxic agents
* No other concurrent investigational drugs
* No concurrent radiotherapy
* Low molecular weight heparin allowed
* More than 7 days since prior CYP3A4 inhibitor therapy
* More than 14 days since prior CYP3A4 inducer therapy
* More than 6 months since prior amiodarone therapy
* More than 14 days since prior St John's Wort, modafinil, ginkgo biloba, kava, grape seed, valerian, ginseng, echinacea and evening primrose oil
18 Years
ALL
No
Sponsors
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Cancer Research UK
OTHER
Roche Pharma AG
INDUSTRY
GlaxoSmithKline
INDUSTRY
Professor David Cunningham
OTHER_GOV
Responsible Party
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Professor David Cunningham
ST03 Chief Investigator, Professor David Cunningham
Principal Investigators
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David Cunningham, MD
Role: STUDY_CHAIR
Royal Marsden NHS Foundation Trust
Locations
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Royal Bournemouth Hospital
Bournemouth, England, United Kingdom
Bradford Royal Infirmary
Bradford, England, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, England, United Kingdom
Addenbrooke's Hospital
Cambridge, England, United Kingdom
Cumberland Infirmary
Carlisle, England, United Kingdom
Doncaster Royal Infirmary
Doncaster, England, United Kingdom
St. Luke's Cancer Centre at Royal Surrey County Hospital
Guildford, England, United Kingdom
Huddersfield Royal Infirmary
Huddersfield, West Yorks, England, United Kingdom
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom
Lincoln County Hospital
Lincoln, England, United Kingdom
Aintree University Hospital
Liverpool, England, United Kingdom
Saint Bartholomew's Hospital
London, England, United Kingdom
St. George's Hospital
London, England, United Kingdom
St. Mary's Hospital
London, England, United Kingdom
Mid Kent Oncology Centre at Maidstone Hospital
Maidstone, England, United Kingdom
Christie Hospital
Manchester, England, United Kingdom
Clatterbridge Centre for Oncology
Merseyside, England, United Kingdom
Northern Centre for Cancer Treatment at Newcastle General Hospital
Newcastle upon Tyne, England, United Kingdom
Derriford Hospital
Plymouth, England, United Kingdom
Dorset Cancer Centre
Poole Dorset, England, United Kingdom
Berkshire Cancer Centre at Royal Berkshire Hospital
Reading, England, United Kingdom
Rochdale Infirmary
Rochdale, England, United Kingdom
Salisbury District Hospital
Salisbury, England, United Kingdom
Wexham Park Hospital
Slough, Berkshire, England, United Kingdom
Southampton General Hospital
Southampton, England, United Kingdom
Royal Marsden - Surrey
Sutton, England, United Kingdom
Aberdeen Royal Infirmary
Aberdeen, Scotland, United Kingdom
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, United Kingdom
Basingstoke and North Hampshire Hospital
Basingstoke, , United Kingdom
Birmingham Heartlands Hospital
Birmingham, , United Kingdom
Castle Hill Hospital
Cottingham, , United Kingdom
University Hospitals Coventry and Warwickshire
Coventry, , United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, , United Kingdom
St James Hospital
Leeds, , United Kingdom
Leicester Royal Infirmary
Leicester, , United Kingdom
Norfolk and Norwich University Hospital
Norwich, , United Kingdom
Churchill Hospital
Oxford, , United Kingdom
Queens Hospital
Romford, , United Kingdom
Weston Park
Sheffield, , United Kingdom
Great Western Hospital
Swindon, , United Kingdom
Musgrove Park Hospital
Taunton, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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Tom Geldart
Role: primary
Stephen J. Falk, MD
Role: primary
Jonathan Wadsley
Role: primary
Gary W. Middleton
Role: primary
Jo Dent
Role: primary
Matthew T. Seymour, MA, MD, FRCP
Role: primary
David Smith, MD
Role: primary
Sarah Slater, MD
Role: primary
Justin Waters, MD
Role: primary
Was Mansoor, MD
Role: primary
David Smith, MD
Role: primary
Fareeda Coxon, MD
Role: primary
Joss Adams, MD
Role: primary
Tim J. Iveson, MD
Role: primary
Marcia Hall, MD
Role: primary
Tim J. Iveson, MD
Role: primary
David Cunningham, MD
Role: primary
Russell Petty, MD
Role: primary
Tom Crosby, MD
Role: primary
References
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Okines AF, Langley RE, Thompson LC, Stenning SP, Stevenson L, Falk S, Seymour M, Coxon F, Middleton GW, Smith D, Evans L, Slater S, Waters J, Ford D, Hall M, Iveson TJ, Petty RD, Plummer C, Allum WH, Blazeby JM, Griffin M, Cunningham D. Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report. Ann Oncol. 2013 Mar;24(3):702-9. doi: 10.1093/annonc/mds533. Epub 2012 Oct 28.
Allum WH, Smyth EC, Blazeby JM, Grabsch HI, Griffin SM, Rowley S, Cafferty FH, Langley RE, Cunningham D. Quality assurance of surgery in the randomized ST03 trial of perioperative chemotherapy in carcinoma of the stomach and gastro-oesophageal junction. Br J Surg. 2019 Aug;106(9):1204-1215. doi: 10.1002/bjs.11184. Epub 2019 Jul 3.
Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, Stevenson L, Grabsch HI, Alderson D, Crosby T, Griffin SM, Mansoor W, Coxon FY, Falk SJ, Darby S, Sumpter KA, Blazeby JM, Langley RE. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017 Mar;18(3):357-370. doi: 10.1016/S1470-2045(17)30043-8. Epub 2017 Feb 3.
Related Links
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Medical Research Council ST03 Clinical Trial Page
Other Identifiers
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MRC-ST03
Identifier Type: OTHER
Identifier Source: secondary_id
EU-20710
Identifier Type: -
Identifier Source: secondary_id
ISRCTN46020948
Identifier Type: OTHER
Identifier Source: secondary_id
2006-000811-12
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
00316/0221/001
Identifier Type: OTHER
Identifier Source: secondary_id
CDR0000536013
Identifier Type: -
Identifier Source: org_study_id