A study to assess whether the addition of an antibody can prevent regrowth of cancer cells in the oesophagus and thereby improve survival.
Oesophageal cancer patients are often treated with chemo-radiotherapy as an alternative to surgery. Although this is an effective method for disease control, patients typically have loco-regional recurrence (disease within the area previously radiated by radiotherapy). This is partially due to radiotherapy resistant cells.
The SCOPE1 trial aimed to assess whether the addition of an antibody called cetuximab, which targets a protein responsible for cell growth on the outside of the cell, may prevent regrowth of cancer cells within the radiated area and ultimately improve overall survival.
SCOPE1 was a randomised phase II/III multicentre clinical trial.
All patients were randomised to receive chemo-radiotherapy with or without cetuximab. Sites were asked to follow a detailed radiotherapy protocol when outlining and planning radiotherapy for SCOPE1 patients. A pre-trial test case was completed by each investigator prior to site activation as a quality assurance measure to ensure standardisation of treatment across the trial.
Involving the public and patients
A patient representative was involved in the design and management of the trial and they attended the regular trial management group meetings. In addition, members of the public were involved in the review of the trial during the funding application process with Cancer Research UK.
The Phase II analysis of the data showed that the addition of cetuximab was less favourable to chemoradiotherapy alone in terms of overall survival and toxicity. This outcome was consistent with other randomised trials conducted at the same time comparing similar types of antibody therapies with standard therapy at other tumour sites.
Although the addition of cetuximab was not recommended, the overall survival in the chemo-radiotherapy arm without cetuximab was higher than previously reported in UK and US studies and even surpassed the rate predicted within the cetuximab arm at the start of the study.
Furthermore, although quality of life scores dropped immediately after treatment, they recovered more quickly than has been found with surgery and, unlike with surgery, there is little lasting deficit.
The successful outcome of this trial was thought to be due to the detailed radiotherapy protocol, the mandated pre-trial radiotherapy quality assurance process and the positive dialogue between the Radiotherapy Trials Quality Assurance (RTTQA) team and the sites.
Study follow up: SCOPE2
Despite the improved patient outcomes seen in SCOPE1 trial, improvement in local-disease control is still needed to prevent patient relapse. To address this, we have developed the SCOPE2 trial which aims to assess whether increasing the dose of radiotherapy within the context of a high-quality RTTQA programme improves overall survival. Additionally, the trial aims to see if survival can be improved by using an early PET scan to change the chemotherapy if it does not appear to be working.
The SCOPE2 radiotherapy protocol has improved upon the SCOPE1 protocol and even more rigorous RTTQA process has been adopted from the NeoSCOPE trial. SCOPE2 also aims to champion the use of the new state-of-the-art radiation delivery system IMRT (intensity modulated radiation therapy) for treating oesophageal cancers at hospitals across the UK.
The SCOPE2 trial is now approved by ethics, the Medicines and Healthcare products Regulatory Agency (MHRA) and global R&D, and can be found on clinicaltrials.gov.
Funder: Cancer Research UK