A randomised phase II/III trial of perioperative 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
Can bevacizumab improve survival in stomach cancer, and can lapatinib help people with a certain type of stomach/oesophageal cancer?
What was this study about?
The ST03 trial is looking at different ways to improve the treatment of people with cancer in their stomach or oesophagus (gullet).
The main ST03 trial is a comparison of epirubicin, cisplatin and capecitabine chemotherapy (ECX) on its own against ECX with bevacizumab (Avastin) in patients with stomach cancer. During the trial, participants will have surgery to remove their cancer. They will receive their trial treatment both before and after this surgery. It is hoped that the addition of bevacizumab to the standard ECX chemotherapy will improve survival in people with stomach cancer. This part of the trial is now closed to recruitment.
Some hospitals which are taking part in the ST03 trial are also participating in the ST03 lapatinib feasibility study. Patients at these hospitals with cancer of the stomach, oesophagus or junction of the stomach and oesophagus will first have a sample of their tumour tested to see if they have high levels of a protein called human epidermal growth factor receptor-2 (HER-2). If this is the case their tumour would be considered HER-2 positive.
If the participant has a HER-2 positive tumour, they may be eligible to enter a different treatment comparison: ECX chemotherapy alone against modified ECX with a drug called lapatinib (Tyverb), which may work well specifically against HER-2 positive tumours (but is not expected to benefit patients with HER-2 negative tumours). Participants will also have surgery during the trial, and will receive treatments at the same time as in the main study.
If the participant has a HER-2 negative stomach cancer, they may still be able to enter one of the imaging sub studies described below.
There are 4 substudies in the ST03 trial, and participants can consent to take part in as many as they wish to (depending on which sub-studies the hospital they attend is participating in).
Alongside the clinical part of the study, the Trans-ST03 sub-study will also collect blood and cancer tissue which will be stored in a laboratory and will be used by authorised researchers in the future to see if we can discover markers in the blood or cancer tissue to help identify which patients will benefit most from different treatments.
In this sub-study we are trying to assess whether MRI (Magnetic Resonance Imaging) scanning can provide additional information about oesophageal and junction cancers. The current techniques used to find out the precise location of the tumour are good and reliable, but we are interested to see whether we can increase and improve the information about the cancer by using MRI. This sub-study is observational and will not affect the treatment a patient receives.
Currently, doctors determine whether cancer is responding to treatment by using blood tests and radiology exams such as Computed Tomography (CT) scans. This sub-study is investigating whether an alternative type of imaging test called a Positron Emission Tomography (PET) scan, can give early indication as to whether chemotherapy is working. This sub-study is observational and will not affect the treatment a patient receives.
Quality of life
Included in ST03 is a quality of life study, to find out how patients feel, both physically and emotionally. Patients will be asked to complete questionnaires at regular intervals throughout the trial.
What difference did this study make?
The main study found that giving patients bevacizumab alongside their chemotherapy did not improve survival. There was no evidence that bevacizumab affects tumour response to chemotherapy, nor the likelihood of having a curative (R0) resection. Furthermore, in patients who underwent oesophagectomy, those who received bevacizumab had a higher rate of a post-operative complication called an anastomotic leak (a leak at the site of the surgical incision) compared to those who received chemotherapy alone.
Despite the lack of a survival benefit with bevacizumab, the data collected in this large study represent a valuable resource to help investigate other research questions in oesophagogastric cancer patients. The results of the other parts of the trial are expected later this year.
Type of study
Who funded the study?
The trial is being funded by the charity Cancer Research UK.
When did it take place?
ST03 began recruitment in 2007 and the results from the main trial were published in 2017. The sub-studies are still ongoing.
Where did it take place?
Hospitals throughout the UK, although not all of these are participating in the feasibility study or substudies.
Who was included?
Main Study (Bevacizumab comparison - now closed to recruitment): people with operable stomach cancers (NB people with oesophageal or oesophagogastric junctional cancers have already been randomised to the main study, but are now no longer eligible following changes to the trial).
Feasibility Study (Lapatinib comparison): people with operable, HER-2 positive cancer of the stomach, oesophagus or junction of the stomach and oesophagus.