LUD2015-005
Research type
Research Study
Full title
Phase 1/2 Study of anti-PD-L1 in Combination with Chemo(radio)therapy for Oesophageal Cancer
IRAS ID
194443
Contact name
Mark Middleton
Contact email
Sponsor organisation
Ludwig Institute for Cancer Research Ltd.
Eudract number
2015-005298-19
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
OCTO-079, Oncology Clinical Trials Office
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
Summary of Research
Drugs that stimulate the immune system to attack tumours are revolutionising treatment for some cancers. Results in oesophageal cancer have not been as exciting as in lung or skin cancer, so the drugs have not replaced existing treatments like chemotherapy and radiotherapy. We don't yet know if giving them with the usual treatments will help. The trial will give a first look at the potential to add durvalumab, a new drug that activates the immune system, to current standard treatments for oesophageal cancer. First we will check that durvalumab can be given safely with chemotherapy in patients with oesophageal cancer that has spread. If this is safe we will then test durvalumab with chemotherapy or chemoradiotherapy given before surgery to patients with potentially curable disease. Depending on how the first part of the trial goes we may also check if we can add a second immunotherapy drug, called tremelimumab, to chemotherapy for inoperable oesophageal cancer. As well as looking at how safe and effective this is we will study the effect of treatment on patients' tumours.
The study will run in several academic centres in the UK, and is sponsored by the Ludwig Institute for Cancer Research, supported by the University of Oxford. Astrazeneca is providing the durvalumab and tremelimumab for the trial.
Patients being treated in the trial will have the usual treatment, lasting 2 to 6 months, but with the new drug(s) added. Durvalumab may also be given after the usual treatment has finished, for up to 6 months.Summary of Results
Oesophageal cancer is the sixth leading cause of cancer deaths world-wide. In western countries, its incidence has risen six-fold in less than 40 years. Oesophageal cancer is often diagnosed late; hence only 23% of cases are suitable for curative surgery, with the cancer coming back in approximately 50% of patients. Hence there is a need for new treatment strategies.
This was a study conducted in the United Kingdom under the coordination of the Department of Oncology, University of Oxford, in patients who had just been diagnosed with oesophageal cancer. Seventy-three patients participated in the study.Two groups of patients were included. One group included patients who had cancer that was located in the oesophagus only and suitable for surgery that could remove all of the cancer. The other group included patients whose disease had spread to areas outside of the oesophagus where removal by surgery was not possible.
Besides initial surgery in suitable cases, the recommended first treatment for patients diagnosed with oesophageal cancer is chemotherapy or chemotherapy together with radiation.
In the first part of the study, patients whose disease had spread were given immunotherapy (durvalumab or durvalumab plus tremelimumab) in addition to the standard chemotherapy. Two different immunotherapies were included in the study because they act by different mechanisms. Durvalumab targets programmed death ligand 1 (PD-L1) and tremelimumab targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). After completion of therapy, the patients were followed to see the effects of the treatment on their cancer.
In the second part of the study, patients with cancer localized in the oesophagus were given durvalumab immunotherapy together with chemotherapy or chemotherapy plus radiation. After completion of immunotherapy plus chemotherapy with or without radiation, the patients underwent surgery to remove the remaining tumor and were followed to see how long they remained cancer free.The purpose of the study was to determine if immunotherapy could be safely administered together with chemotherapy or chemotherapy plus radiation. In addition, patients were followed to determine the effects of treatment on their cancer.
The main objectives of the study were met in that chemotherapy and immunotherapy could be safely administered. In the patients whose cancer had spread outside of the oesophagus, 50% of patients had their tumors decrease in size after completion of treatment. In the patients whose cancer had not spread outside of the oesophagus, 97% went on to have surgery after completion of treatment and 94% of these patients had not progressed 6 months after surgery.
The results of this study show that immunotherapy and chemotherapy with and without radiation can be safety administered together to oesophageal cancer patients with encouraging results and the need for additional studies.REC name
South Central - Hampshire A Research Ethics Committee
REC reference
16/SC/0015
Date of REC Opinion
17 Feb 2016
REC opinion
Further Information Favourable Opinion