Clinical trial NCT01435356: Safety and Efficacy Study of MAGE-A3 + AS-15 in Patients With Muscle-invasive Bladder Cancer After Cystectomy
Official title: A Randomized, Double Blind, Placebo Controlled Phase II Trial to Evaluate the Safety and Efficacy of recMAGE-A3 + AS15 ASCI in Patients With MAGE-A3 Positive Muscle Invasive Bladder Cancer After Cystectomy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Urinary Bladder Neoplasms
Keywords: Urinary Bladder neoplasms
Lymphoproliferative Disorders
Immune System Diseases
Cystectomy
Adjuvants, Immunologic
Immunologic Factors
Lead sponsor: European Association of Urology Research Foundation
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2011-09-16
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this clinical trial was to demonstrate the benefit of the immunotherapeutic product recMAGE-A3 + AS-15 given to patients with bladder cancer after removal of the bladder. A course of 13 injections was administered over 27 months.

Detailed description: This study assessed an investigational treatment for patients with Muscle Invasive Bladder Cancer in whom the urinary bladder had been surgically removed. The investigational treatment aimed to increase the body's immune response to a specific antigen expressed by the cancer. The tumour tissue was first tested whether it expressed the MAGE-A3 antigen.

The MAGNOLIA study was open to male and female patients with pathologically confirmed muscle invasive transitional cell carcinoma of the urinary bladder with expression of the antigen MAGE-A3 with or without limited lymph node involvement who had no evidence of disease after surgery confirmed with imaging procedures (scans CT/MRI).

Eligibility criteria: Inclusion Criteria:

1. Aged greater than or equal to 18 years at the time ICF is signed, either sex.
2. Histologically confirmed (after cystectomy or if needed transurethral resection) urothelial carcinoma of the bladder which is MAGE-A3 positive.
3. Written informed consent for tissue sampling, the mandatory analyses and for the complete study has been obtained prior to the performance of any other protocol-specific procedure.
4. TNM classification at pathological examination of surgically removed specimen: Stage T2,3 N0 or N1 or N2 and M0 disease or Stage T4 N0 M0 disease.
5. The patient is free of residual disease and free of metastasis, as confirmed by a negative baseline Computer Tomogram (CT scan) or Magnetic Resonance Imaging (MRI) of the pelvis, abdomen and chest no more than 13 weeks prior to randomization. Other examinations should be performed as clinically indicated.
6. Patient is fully recovered from surgery within 13 weeks following cystectomy. For patients who receive adjuvant chemotherapy, the patient is fully recovered within 3-6 weeks following chemotherapy.
7. The patient must have adequate bone-marrow reserve, defined as an absolute neutrophil count 1.0 x 109/L, and a platelet count ≥ 75 x 109/L, adequate renal function, defined as a serum creatinine ≤ 1.5 times the Upper Limit of Normal (ULN), and adequate hepatic function, defined as a Total bilirubin ≤ 1.5 times the ULN, and a Alanine transaminase (ALAT) and Aspartate Transaminase (ASAT) ≤ 2.5 times the ULN as assessed by standard laboratory criteria.
8. World Health Organization (WHO) performance status 0 - 1 at the time of randomization.
9. If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to administration of study treatment, have a negative pregnancy test and continue such precautions during all study treatment period and for 2 months after completion of the injection series.
10. The patient should be affiliated to health insurance or benefit of such an insurance

Exclusion Criteria:

1. The patient has previous or concomitant malignancies at other sites except effectively treated non-melanoma skin cancer, cervical carcinoma in situ, incidental localised prostatic carcinoma or effectively treated malignancy that has been in remission for over 5 years.
2. The patient has received any anti cancer systemic treatment, including immunotherapy (local intravesical BCG is allowed), chemotherapy, except:

   * For the treatment of previous malignancies as allowed by the protocol (i.e., non-melanoma skin cancer, cervical carcinoma in situ, incidental localised prostatic carcinoma or effectively treated malignancy that has been in remission for over 5 years).
   * For the treatment with neo-adjuvant chemotherapy for their muscle invasive bladder cancer
   * For the treatment with adjuvant cisplatinum-based chemotherapy for their muscle invasive bladder cancer
3. The patient has received radiotherapy of the abdominal or pelvic region, within 6 months prior to randomization.
4. Women who are pregnant or breast feeding.
5. The patient has a known infection with human immunodeficiency virus (HIV) or chronic hepatitis B or C.
6. The patient has a history of allergic disease or reactions likely to be exacerbated by any component of the study investigational product.
7. The patient has any confirmed or suspected immunosuppressive or immunodeficient condition or potential immune-mediated diseases as. Patients with vitiligo are not excluded to participate in the trial.
8. Patient has received a major organ allograft.
9. The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents. Note: the use of prednisone, or equivalent, \< 0,125 mg/kg/day (absolute maximum 10 mg/day), or inhaled corticosteroids or topical steroids is permitted.
10. The patient has received any investigational or non-registered medicinal product other than the study medication within the 30 days preceding the first dose of study medication, or plans to receive such a drug during the study.
11. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
12. The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk. For example, but not limited to: uncontrolled congestive heart failure or uncontrolled hypertension, unstable heart disease (coronary heart disease or myocardial infarction), uncontrolled arrhythmia or patients taking anticoagulant treatment or having a coagulation disorder.
13. The patient uses alternative treatments eg. plant extracts.
14. Adults under legal supervision

Primary outcomes:
measure: Disease Free Survival
timeFrame: 5 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 5 years
measure: Disease-free Specific Survival
timeFrame: 5 years
measure: Distant Metastasis-free Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Plzen
country: Czechia
facility: Faculty teaching Hospital in Plzen
city: Prague
country: Czechia
facility: Hospital Motol
city: Prague
country: Czechia
facility: Thomayerova nemocnice
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z.
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lille
country: France
facility: Hôpital Huriez
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Paris
country: France
facility: Institut Curie
city: Toulouse
country: France
facility: Hôpital Rangueil
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Dresden
country: Germany
facility: Universitätsklinikum C.-G. Carus Dresden
city: Düsseldorf
country: Germany
facility: Heinrich-Heine University
city: Erlangen
country: Germany
facility: Waldkrankenhaus St. Marien gGmbH
city: Giessen
country: Germany
facility: Universitätsklinikum Giessen
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Mannheim
country: Germany
facility: Universitätsmedizin
city: Marburg
country: Germany
facility: Universitätsklinikum Marburg
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München
city: Rostock
country: Germany
facility: Universitätklinikum Rostock
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Bari
country: Italy
facility: Universitaria Policlinico Consorziale di Bari
city: Milano
country: Italy
facility: Università Vita e Saluta
city: Perugia
country: Italy
facility: Ospedaliera di Perugia
city: Pisa
country: Italy
facility: Universitaria Pisana
city: Rome
country: Italy
facility: Università di Roma, La Sapienza
city: Amsterdam
country: Netherlands
facility: NKI
city: Nieuwegein
country: Netherlands
facility: St Antoniusziekenhuis
city: Nijmegen
country: Netherlands
facility: RadboudUMC
city: Kielce
country: Poland
facility: Kliniczny Dzial Urologii Swietokrzyskiego Centrum Onkologii
city: Warsaw
country: Poland
facility: Medical University of Warsaw
city: Warsaw
country: Poland
facility: Oddzial Urologii Miedzyleski Szpital Specjalistyczny w Warszawie
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Craiova
country: Romania
facility: Clinical County Emergency Hospital Craiova
city: Moscow
country: Russian Federation
facility: Federal State Budget Institution "Scientific Research Institute of Urology" of the Ministry of Healthcare and Social Development of the Russian Federation
city: Moscow
country: Russian Federation
facility: Federal State Institution "Moscow Research Oncology Institute named after P.A. Gertsen" of the Ministry of Healthcare and Social Development of the Russian Federation
city: Moscow
country: Russian Federation
facility: Institution of the Russian Academy of Medical Science Russian Oncology Research Center named after N.N. Blokhin of RAMS
city: Rostov-on-Don
country: Russian Federation
facility: Municipal Budget Institution of Health Care "Clinical Diagnostic Center "Zdorovie" of Rostov-on-Don city"
city: St. Petersburg
country: Russian Federation
facility: Saint Petersburg State Institution of Health Care "City Multi-Field Hospital #2"
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruña
city: Alcalá de Henares
country: Spain
facility: Hospital Universitario Principe de Asturias
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
city: Barcelona
country: Spain
facility: Fundación Puigvert
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Cádiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Madrid
country: Spain
facility: Hospital 12 de Octubre, Fundación de Investigación Biomédica
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: San Sebastián de los Reyes
country: Spain
facility: Hospital Infanta Sofia
city: Kiev
country: Ukraine
facility: Kyiv City Clinical Oncology Hospital
Study officials:
affiliation: EAU Research Foundation
name: Peter FA Mulders, Prof,PhD,MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Colombel M, Heidenreich A, Martinez-Pineiro L, Babjuk M, Korneyev I, Surcel C, Yakovlev P, Colombo R, Radziszewski P, Witjes F, Schipper R, Mulders P, Witjes WP. Perioperative chemotherapy in muscle-invasive bladder cancer: overview and the unmet clinical need for alternative adjuvant therapy as studied in the MAGNOLIA trial. Eur Urol. 2014 Mar;65(3):509-11. doi: 10.1016/j.eururo.2013.10.056. Epub 2013 Nov 11.