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Urinary Bladder NeoplasmsPhase 2MAGNOLIANCT01435356

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

A Phase 2 study testing recMAGE-A3 + AS15 ASCI in people with Urinary Bladder Neoplasms, run by European Association of Urology Research Foundation at 50 sites in 10 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urinary Bladder Neoplasms
What is being tested?
recMAGE-A3 + AS15 ASCI
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
83 participants
Where
50 sitesin 10 countries
Study dates
Aug 2011to 7 Apr 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged greater than or equal to 18 years at the time ICF is signed, either sex.
  • Histologically confirmed (after cystectomy or if needed transurethral resection) urothelial carcinoma of the bladder which is MAGE-A3 positive.
  • 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.
  • 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.
  • 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.
  • 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.
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  • 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.
  • World Health Organization (WHO) performance status 0 - 1 at the time of randomization.
  • 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.
  • The patient should be affiliated to health insurance or benefit of such an insurance

Who cannot join

  • 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.
  • 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
  • The patient has received radiotherapy of the abdominal or pelvic region, within 6 months prior to randomization.
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  • Women who are pregnant or breast feeding.
  • The patient has a known infection with human immunodeficiency virus (HIV) or chronic hepatitis B or C.
  • The patient has a history of allergic disease or reactions likely to be exacerbated by any component of the study investigational product.
  • 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.
  • Patient has received a major organ allograft.
  • 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.
  • 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.
  • The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
  • 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.
  • The patient uses alternative treatments eg. plant extracts.
  • Adults under legal supervision

Trial locations and contacts

50 sites in 10 countries.

50 sites in 10 countries

Germany11 sites

  • Universitätsklinikum Aachen

    Aachen

  • Universitätsklinikum C.-G. Carus Dresden

    Dresden

  • Heinrich-Heine University

    Düsseldorf

  • Waldkrankenhaus St. Marien gGmbH

    Erlangen

  • Universitätsklinikum Giessen

    Giessen

  • Universitätsklinikum Jena

    Jena

  • Universitätsmedizin

    Mannheim

  • Universitätsklinikum Marburg

    Marburg

  • Klinikum rechts der Isar der TU München

    München

  • Universitätklinikum Rostock

    Rostock

  • Universitätsklinikum Tübingen

    Tübingen

Other trials in Germany

Spain11 sites

  • Hospital Universitario A Coruña

    A Coruña

  • Hospital Universitario Principe de Asturias

    Alcalá de Henares

  • Hospital Universitario Fundación Alcorcón

    Alcorcón

  • Fundación Puigvert

    Barcelona

  • Hospital Clinic Barcelona

    Barcelona

  • Hospital del Mar

    Barcelona

  • Hospital Universitario Puerta del Mar

    Cadiz

  • Hospital 12 de Octubre, Fundación de Investigación Biomédica

    Madrid

  • Hospital Universitario La Paz

    Madrid

  • Hospital Universitario Central de Asturias

    Oviedo

  • Hospital Infanta Sofia

    San Sebastián de los Reyes

Other trials in Spain

France5 sites

  • Institut Bergonié

    Bordeaux

  • Hôpital Huriez

    Lille

  • Hôpital Edouard Herriot

    Lyon

  • Institut Curie

    Paris

  • Hôpital Rangueil

    Toulouse

Other trials in France

Italy5 sites

  • Universitaria Policlinico Consorziale di Bari

    Bari

  • Università Vita e Saluta

    Milan

  • Ospedaliera di Perugia

    Perugia

  • Universitaria Pisana

    Pisa

  • Università di Roma, La Sapienza

    Rome

Other trials in Italy

Russia5 sites

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

    Moscow

  • 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

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

    Moscow

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

    Rostov-on-Don

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

    Saint Petersburg

Other trials in Russia

Czechia4 sites

  • Faculty teaching Hospital in Plzen

    Pilsen

  • Hospital Motol

    Prague

  • Thomayerova nemocnice

    Prague

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

    Ústí nad Labem

Other trials in Czechia

Netherlands3 sites

  • NKI

    Amsterdam

  • St Antoniusziekenhuis

    Nieuwegein

  • RadboudUMC

    Nijmegen

Other trials in Netherlands

Poland3 sites

  • Kliniczny Dzial Urologii Swietokrzyskiego Centrum Onkologii

    Kielce

  • Medical University of Warsaw

    Warsaw

  • Oddzial Urologii Miedzyleski Szpital Specjalistyczny w Warszawie

    Warsaw

Other trials in Poland

Romania2 sites

  • Fundeni Clinical Institute

    Bucharest

  • Clinical County Emergency Hospital Craiova

    Craiova

Other trials in Romania

Ukraine1 site

  • Kyiv City Clinical Oncology Hospital

    Kiev

Other trials in Ukraine

About this study

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

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.

Read the 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).

Being tested
recMAGE-A3 + AS15 ASCI, Placebo
Keywords
Urinary Bladder neoplasms, Lymphoproliferative Disorders, Immune System Diseases, Cystectomy, Adjuvants, Immunologic, Immunologic Factors
Medical subject headings
Urinary Bladder Neoplasms, Lymphoproliferative Disorders, Immune System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • recMAGE-A3 + AS15 ASCIBiological

    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

  • PlaceboBiological

    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

Study groups in NCT01435356
Study groupRoleWhat they receive
recMage-A3 + AS15 ASCIActive comparatorMAGE-A3 positive patients treated with recMAGE-A3 + AS15 ASCI
Receives: Biological: recMAGE-A3 + AS15 ASCI
PlaceboPlacebo comparatorMAGE-A3 positive patients treated with placebo
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Free Survival

    To evaluate of the clinical efficacy in terms of Disease Free Survival of treatment versus placebo in the overall population of patients with bladder cancer with MAGE-A3 expression after cystectomy. Disease Free Survival is the time from randomization to either the date of first recurrence of the disease or the date of death (whatever the cause), whichever occurred first. Types of recurrence considered as an event included loco-regional and distant metastases. In addition, any death occurring without prior documentation of tumor recurrence was considered as an event (and was not censored in the statistical analysis) as this approach is less prone to introduce bias.

    Measured: 5 years

Secondary outcomes (3)

  1. Overall Survival

    To evaluate overall survival in the overall study population. Overall Survival was defined as the interval from randomization to the date of death, irrespective of the cause of death; patients still alive were censored at the date of the last assessment.

    Measured: 5 years

  2. Disease-free Specific Survival

    To evaluate Disease-free specific survival in the overall population.Disease-free specific survival was defined as the interval from randomization to the date of first recurrence of disease or date of death due to bladder carcinoma, whichever occurred first. Patients without recurrence or death were censored at the date of last assessment. Patients without recurrence who died from another cause were censored at the date of death.

    Measured: 5 years

  3. Distant Metastasis-free Survival

    To evaluate Distant metastasis-free survival in the overall study population. Distant metastasis-free survival was defined as the interval from randomization to the date of first distant metastasis or date of death, whichever occurred first. Patients alive and without distant metastasis were censored at the date of last assessment.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2011 (estimated)
  2. Study startAug 2011
  3. Primary completion7 Apr 2017
  4. Study completion7 Apr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01435356
Sponsor's protocol ID
EAU RF 2010-01
Other IDs
NTR2846, 2010-024355-85
Acronym
MAGNOLIA
Status last verified
Jan 2019
First submitted
2 Sep 2011
Last updated
9 Jan 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 24268503

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing recMAGE-A3 + AS15 ASCI in people with Urinary Bladder Neoplasms, run by European Association of Urology Research Foundation at 50 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in Germany, Spain, France, Italy, Russia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01435356, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2019.

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