Chemotherapy With or Without Bevacizumab or Lapatinib to Treat Operable Oes... | Recruiting
Chemotherapy With or Without Bevaci... | Recruiting
Chemotherapy With or Without Bevacizumab or Lapatinib to Treat Operable Oesophagogastric Cancer
ST03

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Medical Conditions
  • Oesophagogastric Cancer
Primary Contact Details
Nicholas Kleovoulou
0207 670 4801
See all trial contact details
Recruitment Status
Recruiting
Trial source and source ID number
NCT00450203
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Summary
RATIONALE: Drugs used in chemotherapy, such as epirubicin, cisplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, and small molecule tyrosine kinase inhibitors, such as lapatinib, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Lapatinib targets a specific growth receptor, HER-2. Chemotherapy together with bevacizumab or lapatinib, in HER-2 positive tumours, may kill more tumor cells.

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.
Research Details
  • OBJECTIVES:

    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.
Phase
Phase 2/Phase 3
Study Design
Sorry, this information is not available
Study Type
Interventional
Intervention
Biological : bevacizumab, Drug : capecitabine, Drug : cisplatin, Drug : Epirubicin, Procedure : adjuvant therapy, Procedure : conventional surgery, Procedure : neoadjuvant therapy, Drug : Lapatinib

Study Arm Groups : ECX + Bevacizumab, ECX + Bevacizumab, Epirubicin, Cisplatin and Capecitabine, ECX + Lapatinib, ECX + Bevacizumab, Epirubicin, Cisplatin and Capecitabine, ECX + Lapatinib, ECX + Bevacizumab, Epirubicin, Cisplatin and Capecitabine, ECX + Lapatinib, ECX + Bevacizumab, Epirubicin, Cisplatin and Capecitabine, ECX + Lapatinib, ECX + Bevacizumab, Epirubicin, Cisplatin and Capecitabine, ECX + Lapatinib, ECX + Bevacizumab, Epirubicin, Cisplatin and Capecitabine, ECX + Lapatinib, ECX + Lapatinib

Intervention Type
See Interventions above
Primary Outcome Measures
    Safety; at the end of phase II and phase III; Efficacy; end of trial; Overall survival; end of trial
Secondary Outcome Measures
    Feasibility; end of trial; Treatment-related morbidity; end of trial; Response rates to pre-operative treatment; at phase II review and at end of trial; Surgical resection rates; end of trial; Disease-free survival; end of trial; Quality of life; end of trial; Cost-effectiveness; end of trial; HER-2 Positivity Rate; End of trial; Feasibility of centralised HER-2 testing; After 60 patients tested and then after 110 patients tested and then at end of trial
Publication(s)
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.; 23108952
Result Reports
Check availability of results on the Clinicaltrials.gov website
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Gender
All
Age Range
18 Years - N/A
Who Can Participate
Patients
Number of Participants
1103
Participant Inclusion Criteria
    This is a combined eligibility criteria for both bevacizumab comparison and the lapatinib feasibility study. Please note the bevacizumab comparison closed to recruitment on 28th March 2014.

    DISEASE CHARACTERISTICS:

    - Histologically confirmed gastric or type I, II or III gastroesophageal junction adenocarcinoma or lower oesophageal

    Gastric and Type III junctional tumours should be Stage Ib (T1 N1, T2a/b N0), II, III or stage IV (T4 N1 or N2) with no evidence of distant metastases (M0)

    Lower oesophageal and Type I and II junctional tumours should be Stage II to Stage IVa (T1 N1, T2 N1, T3 N0-1, but not T2N0). T4 (N0 or N1) tumours are also eligible providing that they involve only the crura OR invade only the mediastinal pleura. Patients with nodal disease affecting the origin of the left gastric and splenic artery or coeliac axis (staged as M1a) are also eligible.

    - Resectable disease

    - 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
Participant Exclusion Criteria
This is in the inclusion criteria above
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Trial Location(s)
GSK Investigational Site
London
W2 1NY
Manchester
M20 4BX
Local Institution
Glasgow
Central
Local Institution
Oxford
Oxfordshire
St. George's Hospital
London
England
SW17 0QT
Maidstone Hospital
Maidstone
England
ME16 9QQ
Southampton General Hospital
Southampton
England
SO16 6YD
Royal Marsden - Surrey
Sutton
England
SM2 5PT
Aberdeen Royal Infirmary
Aberdeen
Scotland
AB25 2ZN
Velindre Cancer Center at Velindre Hospital
Cardiff
Wales
CF14 2TL
London
EC1A 7BE
Cambridge
CB2 2QQ
Plymouth
PL6 8DH
St. James University Hospital, Department of Neurology
Leeds
LS9 7TF
Queen Elizabeth Hospital
Birmingham
Sheffield
Doncaster
DN2 5LT
Guildford
GU2 7XX
Liverpool
L9 7AL
Reading
RG1 5AN
Salisbury
SP2 8BJ
Lincoln County Hospital
Lincoln
England
LN2 5QY
Bristol
BS2 8ED
Clatterbridge Centre for Oncology NHS Trust
Birkenhead
England
CH63 4JY
Bradford
BD9 6RJ
Leeds
Norfolk and Norwich University Hospital
Norwich
Royal Bournemouth Hospital
Bournemouth
Dorset
BH7 7DW
Hull Clinical Trials Unit
Cottingham
East Yorkshire
Uni Hospital Leicester
Leicester
Huddersfield Royal Infirmary
Huddersfield
England
HD3 3EA
Great Western Hospital
Swindon
University Hospital
Coventry
Taunton
North Hampshire & Basingstoke Hospital
Basingstoke
Queen's Hospital
Romford
Carlisle
CA2 7HY
Dorset Cancer Centre
Poole
England
BH15 2JB
Wexham Park Hospital
England
SL2 4HL
Northern Centre for Cancer Treatment at Newcastle General Hospital
Newcastle upon Tyne
England
NE4 6BE
Rochdale Infirmary
Rochdale
England
0L12 0NB
Trial Contact(s)
Primary Trial Contact
Nicholas Kleovoulou
0207 670 4801
Other Trial Contacts
Sorry, this information is not available
Countries Recruiting
United Kingdom
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Scientific Title
A Randomised Phase II/III Trial of Peri-Operative Chemotherapy With or Without Bevacizumab in Operable Oesophagogastric Adenocarcinoma and A Feasibility Study Evaluating Lapatinib in HER-2 Positive Oesophagogastric Adenocarcinomas and (in Selected Centres) MRI and PET/CT Sub-studies
EudraCT Number
Not available for this trial
Funder(s)
  • Cancer Research UK
  • Roche Pharma AG
  • GlaxoSmithKline
Other Study ID Numbers
CDR0000536013
Sponsor(s)
Professor David Cunningham
Key Dates

Recruitment Start Date

Oct 2007

Recruitment End Date

Dec 2017

Trial Start Date
Date Not Available
Trial End Date
Date Not Available
Date added to source

20 Mar 2007

Date updated in source

30 Nov 2016