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

Urinary Bladder Neoplasms Clinical Trial

— MAGNOLIA  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01435356
• Other study ID #: EAU RF 2010-01
• Secondary ID: NTR28462010-0243
• Status: Terminated
• Phase: Phase 2
• Start date: August 2011
• Est. completion date: April 7, 2017

Study information

• Verified date: January 2019
• Source: European Association of Urology Research Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 83
• Est. completion date: April 7, 2017
• Est. primary completion date: April 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Urinary Bladder Neoplasms

Intervention

Biological:
• 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
• 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

Locations

Country	Name	City	State
Czechia	Faculty teaching Hospital in Plzen	Plzen
Czechia	Hospital Motol	Prague
Czechia	Thomayerova nemocnice	Prague
Czechia	Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o.z.	Usti nad Labem
France	Institut Bergonié	Bordeaux
France	Hôpital Huriez	Lille
France	Hôpital Edouard Herriot	Lyon
France	Institut Curie	Paris
France	Hôpital Rangueil	Toulouse
Germany	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
Italy	Universitaria Policlinico Consorziale di Bari	Bari
Italy	Università Vita e Saluta	Milano
Italy	Ospedaliera di Perugia	Perugia
Italy	Universitaria Pisana	Pisa
Italy	Università di Roma, La Sapienza	Rome
Netherlands	NKI	Amsterdam
Netherlands	St Antoniusziekenhuis	Nieuwegein
Netherlands	RadboudUMC	Nijmegen
Poland	Kliniczny Dzial Urologii Swietokrzyskiego Centrum Onkologii	Kielce
Poland	Medical University of Warsaw	Warsaw
Poland	Oddzial Urologii Miedzyleski Szpital Specjalistyczny w Warszawie	Warsaw
Romania	Fundeni Clinical Institute	Bucharest
Romania	Clinical County Emergency Hospital Craiova	Craiova
Russian Federation	Federal State Budget Institution "Scientific Research Institute of Urology" of the Ministry of Healthcare and Social Development of the Russian Federation	Moscow
Russian Federation	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
Russian Federation	Institution of the Russian Academy of Medical Science Russian Oncology Research Center named after N.N. Blokhin of RAMS	Moscow
Russian Federation	Municipal Budget Institution of Health Care "Clinical Diagnostic Center "Zdorovie" of Rostov-on-Don city"	Rostov-on-Don
Russian Federation	Saint Petersburg State Institution of Health Care "City Multi-Field Hospital #2"	St. Petersburg
Spain	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	Cádiz
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
Ukraine	Kyiv City Clinical Oncology Hospital	Kiev

Sponsors (2)

Lead Sponsor	Collaborator
European Association of Urology Research Foundation	GlaxoSmithKline

Countries where clinical trial is conducted

Czechia,  France,  Germany,  Italy,  Netherlands,  Poland,  Romania,  Russian Federation,  Spain,  Ukraine, 

References & Publications (1)

Colombel M, Heidenreich A, Martínez-Piñeiro 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	5 years
Secondary	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.	5 years
Secondary	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.	5 years

External Links

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