Molecular screening for cancer treatment
Molecular profiling of tumours match patients with phase I clinical trials
- Date : 12 Nov 2012
- Topic : Anticancer agents & Biologic therapy
Researchers in France are taking advantage of the progress in genetic and molecular characterisation to analyse the profile of individual cancer patients' tumours and, using this information, assign them to particular treatments and phase I clinical trials. In research presented at the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland (6-9 November 2012), Dr Christophe Massard, a medical oncologist and senior consultant in the early drug development unit at the Institut Gustave Roussy in Villejuif, France, described how he and his colleagues have successfully incorporated ‘molecular triaging’ into their phase I clinical trial unit, with results of patients' molecular analyses being made available within three weeks of a sample being taken.
‘Molecular triaging’ - MOSCATO 01 trial
The researchers set up a prospective molecular triage trial in which fresh tumour biopsies were taken from patients with advanced cancer referred to the phase I unit. The study aims at offering patients a molecular profiling of their tumour. This allows the research team to rationally direct those patients to the relevant phase I trials.
The trial is called MOSCATO 01 (MOlecular Screening for CAncer Treatment and Optimisation) and since October 2011 more than 120 patients have been enrolled. Tumour samples were taken with the aid of computerised tomography (CT) or ultra-sound guidance. The researchers analysed the biopsies using comparative genome hybridisation (CGH) to identify changes in the DNA of the tumour, such as mutations, gene deletions or amplifications, or other molecular alterations, and results were available within three weeks. An expert panel of scientists and clinicians reviewed the results to decide on the biological significance of the molecular changes and then referred the patients to the relevant phase I trial where it was available.
Over 95% of patients agreed to join the MOSCATO trial. Molecular analysis has proved feasible in more than 85% of patients, molecular alterations have been detected in half of them and 30% of patients have been allocated so far to a specific trial on the basis of the analysis.
The most important finding at the moment is the feasibility of performing complex molecular characterisation of tumours in daily clinical practice. A hundred patients were enrolled in seven months. For some patients, the results of the analyses changed the phase I trials and treatments for which they were being considered.
The researchers are continuing the trial and aim to enrol a total of 900 patients. According to Dr Massard the approach could be used by other cancer centres but it requires a good, multidisciplinary team, including clinicians, interventional radiologists, pathologists, biologists, bioinformaticians and statisticians, who are available to meet on a regular basis to discuss the results of the molecular analyses.
Examples of targeted anti-cancer drugs where phase I trials have demonstrated the success of selecting patients on the basis of the molecular characterisation of their tumour include: olaparib, a PARP inhibitor, which was used successfully in phase I trials against tumours involving mutations in the BRCA 1/2 genes; vemurafenib used in melanomas with mutations in the BRAF gene; crizotinib in non-small cell lung cancers with translocations in the ALK gene; and vismodegib used in basal-cell carcinoma with mutations in the SMO gene.
The data presented in the poster session have been updated since the published abstract was submitted in June 2012. The research has been funded by private and public donations.
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