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| Sponsor: | Professor David Cunningham |
|---|---|
| Collaborator: |
Cancer Research UK |
| Information provided by (Responsible Party): | Professor David Cunningham, Medical Research Council |
| ClinicalTrials.gov Identifier: | NCT00450203 |
Purpose
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, 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. Giving combination chemotherapy together with bevacizumab 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Oesophagogastric Cancer |
Biological: bevacizumab Drug: capecitabine Drug: cisplatin Drug: epirubicin hydrochloride Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy |
Phase II Phase III |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomized Controlled Phase II/III Trial of Peri-Operative Chemotherapy With or Without Bevacizumab in Operable Oesophagogastric Adenocarcinoma |
| Estimated Enrollment: | 1100 |
| Study Start Date: | October 2007 |
| Estimated Study Completion Date: | December 2016 |
| Estimated Primary Completion Date: | December 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: ECX + Bevacizumab
ECX + Bevacizumab
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Biological: 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.
Drug: 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)
Drug: cisplatin
60mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
Drug: epirubicin hydrochloride
50mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
Procedure: adjuvant therapy
3 cycles of ECX chemotherapy post operatively
Procedure: conventional surgery
Surgery undertaken after 3 cycles of pre-operative chemotherapy. Followed by 3 cycles of chemotherapy.
Procedure: neoadjuvant therapy
3 cycles of pre-operative ECX chemotherapy.
|
|
Active Comparator: ECX
ECX chemotherapy
|
Drug: 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)
Drug: cisplatin
60mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
Drug: epirubicin hydrochloride
50mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)
Procedure: adjuvant therapy
3 cycles of ECX chemotherapy post operatively
Procedure: conventional surgery
Surgery undertaken after 3 cycles of pre-operative chemotherapy. Followed by 3 cycles of chemotherapy.
Procedure: neoadjuvant therapy
3 cycles of pre-operative ECX chemotherapy.
|
OBJECTIVES:
Primary
OUTLINE: This is a multicenter, randomized, open-label, controlled study. Patients are randomized to 1 of 2 treatment arms.
Patients undergo surgery 5-6 weeks after completion of chemotherapy. Patients then receive 3 additional courses of chemotherapy beginning 6-10 weeks after surgery.
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.
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 1,100 patients will be accrued for this study.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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.
PATIENT CHARACTERISTICS:
No prior or concurrent significant medical conditions, including any of the following:
Cardiovascular disease, including the following:
Recent history of any active gastrointestinal inflammatory condition (e.g., peptic ulcer disease, diverticulitis, or inflammatory bowel disease)
No known allergy to any of the following:
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 chronic corticosteroids (≥ 10 mg/day methylprednisolone equivalent)
Contacts and Locations| United Kingdom | |
| Royal Bournemouth Hospital | Recruiting |
| Bournemouth, England, United Kingdom, BH7 7DW | |
| Contact: Tom Geldart 44-1202-726-088 | |
| Bradford Royal Infirmary | Recruiting |
| Bradford, England, United Kingdom, BD9 6RJ | |
| Contact: Sue Cheeseman, MD 44-1274-542-200 | |
| Bristol Haematology and Oncology Centre | Recruiting |
| Bristol, England, United Kingdom, BS2 8ED | |
| Contact: Stephen J. Falk, MD 44-117-928-3074 stephen.falk@ubht.nhs.uk | |
| Addenbrooke's Hospital | Recruiting |
| Cambridge, England, United Kingdom, CB2 2QQ | |
| Contact: Hugo Ford, MD 44-1223-245-151 | |
| Cumberland Infirmary | Recruiting |
| Carlisle, England, United Kingdom, CA2 7HY | |
| Contact: Jonathan J. Nicoll, MD 44-122-881-4688 jonathan.nicoll@ncumbria-acute.nhs.uk | |
| Doncaster Royal Infirmary | Recruiting |
| Doncaster, England, United Kingdom, DN2 5LT | |
| Contact: Jonathan Wadsley 44-1302-366-666 | |
| St. Luke's Cancer Centre at Royal Surrey County Hospital | Recruiting |
| Guildford, England, United Kingdom, GU2 7XX | |
| Contact: Gary W. Middleton 44-1483-570-122 gmiddleton@royalsurrey.nhs.uk | |
| Huddersfield Royal Infirmary | Recruiting |
| Huddersfield, West Yorks, England, United Kingdom, HD3 3EA | |
| Contact: Jo Dent 44-1484-342-000 | |
| Leeds Cancer Centre at St. James's University Hospital | Recruiting |
| Leeds, England, United Kingdom, LS9 7TF | |
| Contact: Matthew T. Seymour, MA, MD, FRCP 44-113-206-6400 | |
| Lincoln County Hospital | Recruiting |
| Lincoln, England, United Kingdom, LN2 5QY | |
| Contact: Zuzana Stokes 44-1522-512-512 | |
| Aintree University Hospital | Recruiting |
| Liverpool, England, United Kingdom, L9 7AL | |
| Contact: David Smith, MD 44-151-525-5980 | |
| St. Mary's Hospital | Recruiting |
| London, England, United Kingdom, W2 1NY | |
| Contact: Danielle Power, MD 44-20-7886-7690 danielle.power@st-marys.nhs.uk | |
| Saint Bartholomew's Hospital | Recruiting |
| London, England, United Kingdom, EC1A 7BE | |
| Contact: Sarah Slater, MD 44-20-7601-8391 | |
| St. George's Hospital | Recruiting |
| London, England, United Kingdom, SW17 0QT | |
| Contact: Tim Benepal, MD 44-208-725-2995 | |
| Mid Kent Oncology Centre at Maidstone Hospital | Recruiting |
| Maidstone, England, United Kingdom, ME16 9QQ | |
| Contact: Justin Waters, MD 44-1622-729-000 | |
| Christie Hospital | Recruiting |
| Manchester, England, United Kingdom, M20 4BX | |
| Contact: Was Mansoor, MD 44-845-226-3000 | |
| Clatterbridge Centre for Oncology | Recruiting |
| Merseyside, England, United Kingdom, CH63 4JY | |
| Contact: David Smith, MD 44-151-334-1155 david.smith@ccotrust.nhs.uk | |
| Northern Centre for Cancer Treatment at Newcastle General Hospital | Recruiting |
| Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE | |
| Contact: Fareeda Coxon, MD 44-191-256-3551 fareeda.coxon@nuth.nhs.uk | |
| Derriford Hospital | Recruiting |
| Plymouth, England, United Kingdom, PL6 8DH | |
| Contact: Sarah Pascoe, MD 44-175-277-7111 | |
| Dorset Cancer Centre | Recruiting |
| Poole Dorset, England, United Kingdom, BH15 2JB | |
| Contact: Richard Osborne, MD, FRCP 44-1-202-448-265 | |
| Berkshire Cancer Centre at Royal Berkshire Hospital | Recruiting |
| Reading, England, United Kingdom, RG1 5AN | |
| Contact: Joss Adams, MD 44-118-322-7878 | |
| Rochdale Infirmary | Recruiting |
| Rochdale, England, United Kingdom, 0L12 0NB | |
| Contact: Khurshid Akhtar, MD 44-170-637-7777 | |
| Salisbury District Hospital | Recruiting |
| Salisbury, England, United Kingdom, SP2 8BJ | |
| Contact: Tim J. Iveson, MD 44-1722-336-262 ext. 4688 | |
| Wexham Park Hospital | Recruiting |
| Slough, Berkshire, England, United Kingdom, SL2 4HL | |
| Contact: Marcia Hall, MD 44-1753-634-364 marcia.hall@nhs.net.uk | |
| Southampton General Hospital | Recruiting |
| Southampton, England, United Kingdom, SO16 6YD | |
| Contact: Tim J. Iveson, MD 44-23-8079-6802 t.iveson@soton.ac.uk | |
| Royal Marsden - Surrey | Recruiting |
| Sutton, England, United Kingdom, SM2 5PT | |
| Contact: David Cunningham, MD 44-20-8661-3279 david.cunningham@rmh.nhs.uk | |
| Aberdeen Royal Infirmary | Recruiting |
| Aberdeen, Scotland, United Kingdom, AB25 2ZN | |
| Contact: Russell Petty, MD 44-84-5456-6000 | |
| Velindre Cancer Center at Velindre Hospital | Recruiting |
| Cardiff, Wales, United Kingdom, CF14 2TL | |
| Contact: Tom Crosby, MD 44-29-2031-6292 | |
| Study Chair: | David Cunningham, MD | Royal Marsden NHS Foundation Trust |
More Information
| Responsible Party: | Professor David Cunningham, ST03 Chief Investigator, Professor David Cunningham, Medical Research Council |
| ClinicalTrials.gov Identifier: | NCT00450203 History of Changes |
| Other Study ID Numbers: | CDR0000536013, MRC-ST03, EU-20710, ISRCTN46020948, EUDRACT-2006-000811-12, CTA-00316/0221/001 |
| Study First Received: | March 20, 2007 |
| Last Updated: | January 27, 2012 |
| Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
|
adenocarcinoma of the stomach adenocarcinoma of the gastro oesophageal junction adenocarcinoma of the lower oesophagus |
|
Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Capecitabine Bevacizumab Cisplatin Epirubicin Antineoplastic Agents Therapeutic Uses |
Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Antibiotics, Antineoplastic Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |