Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Capecitabine

Bevacizumab

Cisplatin

Epirubicin

Lapatinib

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

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.

bevacizumab

dose banded as based on patient BSA. Oral dose given twice a day during each 21 day cycle of chemotherapy (6 cycles in total)

capecitabine

60mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)

cisplatin

50mg/m2 IV day one of each 21 day cycle of chemotherapy (6 cycles in total)

3 cycles of ECX chemotherapy post operatively

adjuvant therapy

Surgery undertaken after 3 cycles of pre-operative chemotherapy. Followed by 3 cycles of chemotherapy.

conventional surgery

3 cycles of pre-operative ECX chemotherapy.

neoadjuvant therapy

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.

Nicholas Kleovoulou

Tom Geldart

Stephen J. Falk, MD

Jonathan Wadsley

Gary W. Middleton

Jo Dent

Matthew T. Seymour, MA, MD, FRCP

David Smith, MD

Sarah Slater, MD

Justin Waters, MD

Was Mansoor, MD

Fareeda Coxon, MD

Joss Adams, MD

Tim J. Iveson, MD

Marcia Hall, MD

David Cunningham, MD

Russell Petty, MD

Tom Crosby, MD

Charlotte Rees

Mohan Hingorani

Sharmila Sothi

Janet Graham

Matt Seymour

Anne Thomas

Tom Roques

Kinnari Patel

Sherif Raouf

Suzanne Darby

Claire Blesing

Emma Cattell

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.

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.

Chemotherapy With or Without Bevacizumab or Lapatinib to Treat Operable Oesophagogastric Cancer

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

Cancer Research UK

Roche Pharma AG

GlaxoSmithKline

Professor David Cunningham

ST03 Chief Investigator, Professor David Cunningham

Adult patients referred for oesophago-gastro-duodenoscopy (OGD) to investigate any of the following symptoms: difficulty swallowing, vomiting, reflux, anaemia, gastrointestinal (GI) bleeding, upper abdominal pain and weight loss.

Adult patients with known BO who are undergoing OGD for surveillance

Adult patients who have been diagnosed with OGc (Ac or SCc) and are having further investigations as part of the disease staging process such as a staging laparoscopy or further OGD

Adult patients with OGc (Ac or SCc) who are having surgical resection of the cancer

No intervention sample collection only

Subhir Bedi

Chris Groves

Mark Brandon-Grove

Sacheen Kumar

Nikhil Patel

The number of cases of oesophagogastric cancer is increasing every year. Currently, only 39% of patients with oesophageal cancer can have potentially curative treatment by the time they are diagnosed. This is because it typically presents late, and it is only when patients start to develop symptoms of advanced disease such as difficulty swallowing and weight loss, that they seek medical attention.

There are approximately 9300 new cases of oesophageal cancer in the UK each year and at 17%, it has the 5th poorest 5-year survival of all cancers in the UK.

It is diagnosed by carrying out a camera test called a gastroscopy which allows a biopsy of the cancer to be taken. This is an invasive procedure, and unlike for other types of cancer, such as bowel cancer, there is no test to risk-stratify patients at an earlier stage. Risk-stratification enables patients more likely to develop oesophagogastric cancer to be identified, which allows them to have more focused follow-up. This can potentially enable cancer to be diagnosed earlier, before the disease becomes more advanced, allowing patients to have potentially curative treatment.

Scientific research has identified that the healthy bacteria in the oesophagus and stomach changes as oesophagogastric cancer develops. The investigators want to see if similar changes can be identified in the healthy bacteria in the mouth which could be indicative of cancer developing in the oesophagus or stomach. The investigators then hope to use this information to develop a non-invasive risk-stratification tool that can be used to diagnose oesophagogastric cancer earlier and thereby enable more patients to be cured.

The purpose of this study is to investigate the interplay between immune pathways, the mucosal barrier and microbiome in oesophagogastric cancer, with the intention of identifying biologically-plausible biomarkers implicated in oesophagogastric carcinogenesis. The long-term translational objective of this work is to develop a non-invasive risk-stratification test with the aim of identifying patients at risk of developing, or with possible early oesophagogastric cancer, who can then undergo diagnostic testing with the intention of identifying early, potentially curable disease.

In order to do this, a deep understanding of the microbiome, the immune pathways, and ensuing changes at the level of the oesophagogastric mucosa is required. This work aligns with one of the cornerstones of improving survival in OGc; early diagnosis.

* Saliva
* Buccal mucosa swabs
* OG mucus
* OG mucosal biopsies
* Gastric fluid
* Surgically resected specimens of primary OG tumours

IMaC - Immune Pathways in Oesophagogastric Cancer

Investigation of Immune Pathways and Microbiome Disruption as Drivers of Mutagenesis in Oesophagogastric Cancer

Identification of a novel biomarker detectable in salivary samples or buccal swabs from the oropharynx, that can be used as a marker of downstream neoplastic changes leading to oesophagogastric carcinoma.

Profile the oropharyngeal microbiome and mucin perturbations occurring across the spectrum of pre-malignant oesophgagogastic disease (Barrett's Oesophagus) and oesophagogastric cancers, including controls with no endoscopic evidence of upper Gastrointestinal (GI) pathology i.e. a normal upper GI tract, negative Helicobacter pylori tests and patients with GORD

Comprehensive understanding of altered immune pathways driving oesophageal cancer and their relation to microbiota and mucus perturbations to provide targets for mechanistic investigation within experimental models

Gain understanding of key pathways driving oesophageal carcinogenesis, insights that are essential for developing robust biologically-plausible early biomarkers with high clinical predictive value, through the use of in vitro models

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemotherapy With or Without Bevacizumab or Lapatinib to Treat Operable Oesophagogastric Cancer	NCT00450203	Oesophagogastri...	bevacizumab capecitabine cisplatin Epirubicin adjuvant therap... conventional su... neoadjuvant the... Lapatinib	18 Years -	Medical Research Council
IMaC - Immune Pathways in Oesophagogastric Cancer	NCT06057220	Oesophagogastri...	No intervention...	17 Years -	Royal Marsden NHS Foundation Trust
Chemotherapy With or Without Bevacizumab or Lapatinib to Treat Operable Oesophagogastric Cancer	NCT00450203	Oesophagogastri...	bevacizumab capecitabine cisplatin Epirubicin adjuvant therap... conventional su... neoadjuvant the... Lapatinib	18 Years -	Medical Research Council

Spots Global Cancer Trial Database for oesophagogastric cancer