Safety and Efficacy Study of MAGE-A3 + AS-15 in Patients With Muscle-invasive Bladder Cancer After Cystectomy

NCT ID: NCT01435356

Last Updated: 2019-01-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2017-04-07

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).

Conditions

Urinary Bladder Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

recMage-A3 + AS15 ASCI

MAGE-A3 positive patients treated with recMAGE-A3 + AS15 ASCI

Group Type: ACTIVE_COMPARATOR

recMAGE-A3 + AS15 ASCI

Intervention Type: BIOLOGICAL

5 doses were administered (intramuscular) at 3-week intervals followed by 8 doses administered at 3-month intervals for a total maximum duration of study treatment administration of 27 months

Placebo

MAGE-A3 positive patients treated with placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

5 doses were administered (intramuscular) at 3-week intervals followed by 8 doses administered at 3-month intervals for a total maximum duration of study treatment administration of 27 months

Interventions

recMAGE-A3 + AS15 ASCI

5 doses were administered (intramuscular) at 3-week intervals followed by 8 doses administered at 3-month intervals for a total maximum duration of study treatment administration of 27 months

Intervention Type: BIOLOGICAL

Placebo

5 doses were administered (intramuscular) at 3-week intervals followed by 8 doses administered at 3-month intervals for a total maximum duration of study treatment administration of 27 months

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

European Association of Urology Research Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter FA Mulders, Prof,PhD,MD

Role: PRINCIPAL_INVESTIGATOR

EAU Research Foundation

Locations

Faculty teaching Hospital in Plzen

Pilsen, , Czechia

Hospital Motol

Prague, , Czechia

Thomayerova nemocnice

Prague, , Czechia

Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z.

Ústí nad Labem, , Czechia

Institut Bergonié

Bordeaux, , France

Hôpital Huriez

Lille, , France

Hôpital Edouard Herriot

Lyon, , France

Institut Curie

Paris, , France

Hôpital Rangueil

Toulouse, , France

Universitätsklinikum Aachen

Aachen, , Germany

Universitätsklinikum C.-G. Carus Dresden

Dresden, , Germany

Heinrich-Heine University

Düsseldorf, , Germany

Waldkrankenhaus St. Marien gGmbH

Erlangen, , Germany

Universitätsklinikum Giessen

Giessen, , Germany

Universitätsklinikum Jena

Jena, , Germany

Universitätsmedizin

Mannheim, , Germany

Universitätsklinikum Marburg

Marburg, , Germany

Klinikum rechts der Isar der TU München

München, , Germany

Universitätklinikum Rostock

Rostock, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Universitaria Policlinico Consorziale di Bari

Bari, , Italy

Università Vita e Saluta

Milan, , Italy

Ospedaliera di Perugia

Perugia, , Italy

Universitaria Pisana

Pisa, , Italy

Università di Roma, La Sapienza

Rome, , Italy

NKI

Amsterdam, , Netherlands

St Antoniusziekenhuis

Nieuwegein, , Netherlands

RadboudUMC

Nijmegen, , Netherlands

Kliniczny Dzial Urologii Swietokrzyskiego Centrum Onkologii

Kielce, , Poland

Medical University of Warsaw

Warsaw, , Poland

Oddzial Urologii Miedzyleski Szpital Specjalistyczny w Warszawie

Warsaw, , Poland

Fundeni Clinical Institute

Bucharest, , Romania

Clinical County Emergency Hospital Craiova

Craiova, , Romania

Federal State Budget Institution "Scientific Research Institute of Urology" of the Ministry of Healthcare and Social Development of the Russian Federation

Moscow, , Russia

Federal State Institution "Moscow Research Oncology Institute named after P.A. Gertsen" of the Ministry of Healthcare and Social Development of the Russian Federation

Moscow, , Russia

Institution of the Russian Academy of Medical Science Russian Oncology Research Center named after N.N. Blokhin of RAMS

Moscow, , Russia

Municipal Budget Institution of Health Care "Clinical Diagnostic Center "Zdorovie" of Rostov-on-Don city"

Rostov-on-Don, , Russia

Saint Petersburg State Institution of Health Care "City Multi-Field Hospital #2"

Saint Petersburg, , Russia

Hospital Universitario A Coruña

A Coruña, , Spain

Hospital Universitario Principe de Asturias

Alcalá de Henares, , Spain

Hospital Universitario Fundación Alcorcón

Alcorcón, , Spain

Fundación Puigvert

Barcelona, , Spain

Hospital Clinic Barcelona

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital Universitario Puerta del Mar

Cadiz, , Spain

Hospital 12 de Octubre, Fundación de Investigación Biomédica

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Central de Asturias

Oviedo, , Spain

Hospital Infanta Sofia

San Sebastián de los Reyes, , Spain

Kyiv City Clinical Oncology Hospital

Kiev, , Ukraine

Countries

Czechia; France; Germany; Italy; Netherlands; Poland; Romania; Russia; Spain; Ukraine

References

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.

Reference Type: BACKGROUND

PMID: 24268503 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.ncbi.nlm.nih.gov/pubmed/24268503

Pubmed

Other Identifiers

NTR2846

Identifier Type: REGISTRY

Identifier Source: secondary_id

2010-024355-85

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EAU RF 2010-01

Identifier Type: -

Identifier Source: org_study_id