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

NCT01435356 | Terminated Phase 2 Results DMC

• 3 other identifiers: EAU RF 2010-01NTR28462010-024355-85
• Study Type: interventional
• Target: 83
• Locations: 10 countries
• Sites: 50

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.

Conditions

Urinary Bladder Neoplasms

Keywords

Urinary Bladder neoplasms; Lymphoproliferative Disorders; Immune System Diseases; Cystectomy; Adjuvants, Immunologic; Immunologic Factors

Outcome Measures

Primary Outcomes (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.

  5 years

Secondary Outcomes (3)

• Overall Survival

  5 years

• Disease-free Specific Survival

  5 years

• Distant Metastasis-free Survival

  5 years

Study Arms (2)

recMage-A3 + AS15 ASCI

ACTIVE COMPARATOR

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

Biological: recMAGE-A3 + AS15 ASCI

Placebo

PLACEBO COMPARATOR

MAGE-A3 positive patients treated with placebo

Biological: Placebo

Interventions

recMAGE-A3 + AS15 ASCI 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

recMage-A3 + AS15 ASCI

Placebo 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• European Association of Urology Research Foundation: lead
• GlaxoSmithKline: collaborator

Study Sites (50)

Faculty teaching Hospital in Plzen

Pilsen, Czechia

Location

Hospital Motol

Prague, Czechia

Location

Thomayerova nemocnice

Prague, Czechia

Location

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

Ústí nad Labem, Czechia

Location

Institut Bergonié

Bordeaux, France

Location

Hôpital Huriez

Lille, France

Location

Hôpital Edouard Herriot

Lyon, France

Location

Institut Curie

Paris, France

Location

Hôpital Rangueil

Toulouse, France

Location

Universitätsklinikum Aachen

Aachen, Germany

Location

Universitätsklinikum C.-G. Carus Dresden

Dresden, Germany

Location

Heinrich-Heine University

Düsseldorf, Germany

Location

Waldkrankenhaus St. Marien gGmbH

Erlangen, Germany

Location

Universitätsklinikum Giessen

Giessen, Germany

Location

Universitätsklinikum Jena

Jena, Germany

Location

Universitätsmedizin

Mannheim, Germany

Location

Universitätsklinikum Marburg

Marburg, Germany

Location

Klinikum rechts der Isar der TU München

München, Germany

Location

Universitätklinikum Rostock

Rostock, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Universitaria Policlinico Consorziale di Bari

Bari, Italy

Location

Università Vita e Saluta

Milan, Italy

Location

Ospedaliera di Perugia

Perugia, Italy

Location

Universitaria Pisana

Pisa, Italy

Location

Università di Roma, La Sapienza

Rome, Italy

Location

NKI

Amsterdam, Netherlands

Location

St Antoniusziekenhuis

Nieuwegein, Netherlands

Location

RadboudUMC

Nijmegen, Netherlands

Location

Kliniczny Dzial Urologii Swietokrzyskiego Centrum Onkologii

Kielce, Poland

Location

Medical University of Warsaw

Warsaw, Poland

Location

Oddzial Urologii Miedzyleski Szpital Specjalistyczny w Warszawie

Warsaw, Poland

Location

Fundeni Clinical Institute

Bucharest, Romania

Location

Clinical County Emergency Hospital Craiova

Craiova, Romania

Location

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

Moscow, Russia

Location

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

Location

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

Moscow, Russia

Location

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

Rostov-on-Don, Russia

Location

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

Saint Petersburg, Russia

Location

Hospital Universitario A Coruña

A Coruña, Spain

Location

Hospital Universitario Principe de Asturias

Alcalá de Henares, Spain

Location

Hospital Universitario Fundación Alcorcón

Alcorcón, Spain

Location

Fundación Puigvert

Barcelona, Spain

Location

Hospital Clinic Barcelona

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitario Puerta del Mar

Cadiz, Spain

Location

Hospital 12 de Octubre, Fundación de Investigación Biomédica

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Spain

Location

Hospital Infanta Sofia

San Sebastián de los Reyes, Spain

Location

Kyiv City Clinical Oncology Hospital

Kiev, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 24268503 BACKGROUND

Related Links

• Pubmed

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Lymphoproliferative Disorders; Immune System Diseases

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Limitations and Caveats

Trial's recruitment was prematurely stopped. The recMAGE-A3+ AS15 patients were given the opportunity to continue treatment whereas placebo patients needed to stop treatment. All clinical data collected in this study were analysed descriptively.

Results Point of Contact

• Title: Wim P.J. Witjes, MD, PhD Scientific and Clinical Research Director
• Organization: EAU Research Foundation

w.witjes@uroweb.org

+31 26 389 0677

Study Officials

• Peter FA Mulders, Prof,PhD,MD

  EAU Research Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2011
• First Posted: September 16, 2011
• Study Start: August 1, 2011
• Primary Completion: April 7, 2017
• Study Completion: April 7, 2017
• Last Updated: January 9, 2019
• Results First Posted: January 9, 2019

Record last verified: 2019-01

Locations

FR (5); PL (3); ES (11); RO (2); CZ (4); DE (11); IT (5); NL (3); RU (5); UA (1)