Three European cancer centres in Paris (Institut Gustave Roussy), Amsterdam (Netherlands Cancer Institute) and in Stockholm (Karolinska Institutet), have joined forces in their battle against cancer. In a collaborative effort, the European Comprehensive Cancer Centre Alliance (ECCCA) strives to develop and implement innovative strategies to improve cancer cure and reduce treatment related side effects. With a strong focus on combining rationally designed targeted agents with radiotherapy, ECCCA brings together powerful technological platforms of genomics, proteomics and preclinical evaluation tools to identify promising agents for combined application in early clinical trials. On September 5th this cooperation will start with an inauguration symposium, organised at the NKI, where ECCCA will present its strategic plan, technical platforms and will announce the first three clinical translational trials that will be activated in the three participating centres.
Innovative trials
The cooperation will start immediately with a number of innovative trials. Each institute has submitted a trial that will be executed in all three institutes. In the trials, findings from the lab are “directly” brought into the clinic for evaluating their clinical efficacy. The combined knowledge and facilities in the field of fundamental, translational and clinical research means that it is possible to make rapid progress in this respect. All three trials are characterized by the combination of innovative radiation techniques with translational research.
Image guided Radiotherapy
The trial of the NKI-AVL is aimed at a new concept in breast-conserving treatment. During this treatment only the tumour, rather than the whole breast, is irradiated. A short irradiation schedule will be applied, while using image-guided techniques with a CT scan on the linear accelerator (Image Guided Accelerated Partial Breast Irradiation). The tumour response to treatment will be measured with PET and MRI spectrometry. Simultaneously, genetic analysis is done on the tumour tissue, whereby the response to the treatment is scored. It is anticipated that by looking at the response, it can be predicted which patients are suitable for this limited short treatment. The genetic changes during the radiation will also indicate which drugs may enhance the cell-killing effect of radiation.
Stereotactic Body radiotherapy (SBRT) in advanced lung cancer as an adjunctive to pharmaceutical treatment
With SBRT, tumours can be irradiated with high precision, sparing damage to surrounding healthy tissue. This technology was pioneered at Karolinska and is now being tested for various tumour indications. In this study, initiated by Karolinska, SBRT will be given to both primary tumours and metastatic locations, followed by conventional chemotherapy. The goal is to control tumours in locations that can be identified by novel imaging techniques (PET/CT). After SBRT the tumour disease will return to a less advanced stage, for which chemotherapy will be more effective. The goal of the treatment is to substantially prolong the patient’s survival and also to counteract tumour related symptoms.
Inhibition of the PI3-kinase/AKT/mTOR axis during Radiotherapy
Of the molecular anomalies identified in non-small cell lung cancer, EGFr mutation or overexpression, mutations of the RAS oncogene or the PTEN tumour suppressor gene are among the most frequently observed. All of these alterations signal through the PI3-kinase/AKT/mTOR pathway, which is critical for tumour escape from radiation induced cell death.
This trial initiated by IGR, aims at combining radiotherapy for locally advanced non small cell cancer (non metastatic,) sequential radio-chemotherapy and everolimus, an inhibitor of mTOR (RAD001). The first objective is to assess the safety of the combination. In parallel, prospective functional and metabolic imaging will be used (angio scanner and PET) to monitor tumour response. Tumour tissue will also be prospectively collected to define molecular patterns of responding tumours.
Three Top Institutes
The three participating institutes within the ECCCA are perfectly complementary to each other. The NKI-AVL consists of a high quality scientific research institute and a specialized oncology clinic. The Institut Gustave Roussy is a large cancer institute in Paris, providing high quality patient care, combined with scientific research and education. The Swedish Karolinska Institutet is exceptional in combining large translational and fundamental research facilities in the oncology field, with an oncological university clinic. The unique combination of expertises in the field of fundamental and applied research supports innovative research plans. The availability of a large number of patients and a good infrastructure allow the execution of these sophisticated trials.
More information on the other trials and the cooperation can be found on www.eccca.eu (online September 5th 2008).