The MAGNOLIA study is a multicentre, prospective, placebo-controlled, parallel group, double-blinded phase II trial in which the safety and efficacy of Cancer Immunotherapy (CI) with the investigational compound recMAGE-A3 + AS15 in patients with muscle invasive bladder cancer (MIBC) after radical cystectomy is evaluated.
This study is the first European bladder cancer study sponsored by the non-commercial EAU Research Foundation and the only European study evaluating a Cancer Antigen Specific Immunotherapy in patients after cystectomy.
Ten countries (Germany, France, Spain, Italy, the Netherlands, Poland, Czech Republic, Ukraine, Romania and Russia) are participating with a total of 51 active centres. Three new MAGNOLIA centres will be opened, one in Germany (Dr. Bolenz, Mannheim) and two in Spain (Dr. Villacampa, Madrid; Prof. Morote, Barcelona). As of press time (cut-off date November 25, 2013) 423 patients gave their consent, 327 tumour tissue samples were screened, of which 52% were positive for MAGE-A3, and 65 patients (54 male and 11 female patients) were randomised. Pathological T-stage was T2, T3 or T4 in 28, 28 and 9 patients, respectively, whereas the pN-stage was N0, N1 or N2 in 50, 8 and 7 patients, respectively. A total of 24 (37%) patients had pT4 tumours or N+ disease.
The randomisation arms were equally distributed with regards to prognostic groups and centres. The randomised patients are representative for the MIBC population after radical cystectomy. All tumours express MAGE-A3 and 37% of the patients have extravesical or node-positive disease and hence are at high risk for developing disease relapse. Fifty-eight patients received in total 331 injections. For the patients currently enrolled, the MAGE-A3 cancer immunotherapeutic showed a clinically acceptable safety profile with no unexpected safety concerns.
Investigators collaborate to optimise recruitment
The MAGNOLIA study is challenging and involves different disciplines (urology, oncology, radiology and pathology) and is targeted at a complex patient population. Therefore, the MAGNOLIA team organises, at a national level, teleconferences and face-to-face meetings to discuss the country-specific recruitment challenges and to exchange ideas how to organize, identify and manage patients for the study. Recently, national teleconferences have been held in Czech Republic (22 October 2013) and Italy 19 November 2013).
Following the National Meeting for Germany (25th of September 2013 in Dresden, German), a meeting for the participating sites in Russia was held on the 6th of November 2013 in Moscow, Russia, concurrently held with the 13th Congress of Russian Association of Urology. The participants were Prof. Igor Korneyev (St. Petersburg), Dr. Maria Peters (Moscow), Dr. Maksim Golovaschenko (Moscow), Dr. Kirill Nyushko (Moscow), Mrs.Yulia Polevay (Moscow), Dr. Nikolay Keshishev (Moscow), Dr. Andrey Koryakin (Moscow) and Dr. Armen Galstyan (Rostov-on-Don).
The main obstacle for recruitment, as mentioned by the site staff, was the relatively short time between cystectomy and randomization (a maximum of nine weeks after cystectomy). It was recommended that both ICFs (for Screening and Study Participation) could be signed before cystectomy, and the nineweek period can be prolonged (up to 12 weeks).
The meeting was well received and the sites have started identifying and screening eligible patients. To increase the public awareness of the MAGNOLIA trial the members of the Steering Committee (Prof. M. Colombel, Prof. A. Heidenreich, Prof. L. Martínez- Piñeiro, Prof. M. Babjuk, Prof. I. Korneyev, Ass. Prof. C. Surcel, Prof. P. Yakovlev, Prof. R. Colombo, Prof. P. Radziszewski, Prof. F. Witjes, Dr. R. Schipper, Prof. P. Mulders, Dr. W. Witjes) collaborated on an editorial article entitled ”Perioperative Chemotherapy in Muscle-invasive Bladder Cancer: Overview and the Unmet Clinical Need for Alternative Adjuvant Therapy as Studied in the MAGNOLIA Trial“ which will be published in European Urology.