Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00003996

Trial Description

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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

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Trial Acronym

MAGNOLIA

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URL of the Trial

[---]*

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Brief Summary in Lay Language

The purpose of this clinical trial is 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 will be administered over 27 months.

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Brief Summary in Scientific Language

This study will assess an investigational treatment for patients with Muscle Invasive
Bladder Cancer in whom the urinary bladder has been surgically removed. The investigational
treatment aims to increase the body's immune response to a specific antigen expressed by the
cancer. The tumour tissue will first be tested whether it expresses the MAGE-A3 antigen.

The MAGNOLIA study is 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 have no evidence of disease after
surgery confirmed with imaging procedures (scans CT/MRI).

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Organizational Data

  •   DRKS00003996
  •   2012/08/29
  •   2011/09/02
  •   yes
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Secondary IDs

  •   2010-024355-85 
  •   NCT01435356  (ClinicalTrials.gov)
  •   EAU RF 2010-01  (European Association of Urology Research Foundation)
  •   NTR2846 
  •   2010-024355-85 
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Health Condition or Problem studied

  •   Urinary Bladder Neoplasms
  •   C67 -  Malignant neoplasm of bladder
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Interventions/Observational Groups

  •   Biological: recMAGE-A3 + AS15 ASCI
  •   Biological: Placebo
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, caregiver, investigator/therapist, assessor
  •   Placebo, Active control (effective treament of control group)
  •   Prevention
  •   Parallel
  •   II
  •   [---]*
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Primary Outcome

- Disease free survival; time frame: 5 years; 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

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Secondary Outcome

- Overall survival; time frame: 5 years; To evaluate overall survival in the overall study population, in the subpopulations with and without use of neo-adjuvant chemotherapy and in the subpopulations with and without use of adjuvant chemotherapy
- Disease-free survival (DFS); time frame: 5 years; To evaluate Disease-free (DFS) in the subpopulations with and without use of neo-adjuvant chemotherapy and in the subpopulations with and without use of adjuvant chemotherapy
- Disease-free specific survival (DFSS); time frame: 5 years; To evaluate Disease-free specific survival (DFSS) in the overall study population, in the subpopulations with and without use of neo-adjuvant chemotherapy and in the subpopulations with and without use of adjuvant chemotherapy
- Distant metastasis-free survival (DMFS); time frame: 5 years; To evaluate Distant metastasis-free survival (DMFS) in the overall study population, in the subpopulations with and without use of neo-adjuvant chemotherapy and in the subpopulations with and without use of adjuvant chemotherapy
- (Serious) Adverse events; time frame: 5 Years; To evaluate the safety of recMAGE-A3 + AS15 ASCI in the overall study population, in the subpopulations with and without use of neo-adjuvant chemotherapy and in the subpopulations with and without use of adjuvant chemotherapy
- Immune response to recMAGE-A3 + AS15 ASCI; time frame: 5 years; To evaluate the immune response to recMAGE-A3 + AS15 ASCI in the overall study population, in the subpopulations with and without use of neo-adjuvant chemotherapy and in the subpopulations with and without use of adjuvant chemotherapy
- Translational research on gene signature and expression; time frame: 5 years; Evaluation of the tumoral gene expression profiles by microarray analysis on total mRNA extracts from the primary tumor
- Translational research on gene signature and expression; time frame: 5 Years; To evaluate on exploratory basis a possible correlation between gene expression profile of the primary tumor and clinical efficacy of recMAGE-A3 + AS15 ASCI compared to placebo in terms of Disease-free Survival (DFS) and Overall survival.
- Translational research on gene signature and expression; time frame: 5 Years; To evaluate expression of genes in a previously identified gene signature and evaluate their correlation with clinical efficacy of recMAGE-A3 + AS15 ASCI compared to placebo in terms of Disease-free Survival (DFS), Overall survival, Disease-free specific survival (DFSS), Distant metastasis-free survival (DMFS).
- Translational Research on tumor microenvironment and lymphocyte infiltration; time frame: 5 years; To characterize the tumor microenvironment and lymphocyte infiltration in the primary tumor and its recurrence lesions

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Countries of Recruitment

  •   Czech Republic
  •   France
  •   Germany
  •   Italy
  •   Netherlands
  •   Romania
  •   Russian Federation
  •   Spain
  •   Ukraine
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Locations of Recruitment

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Recruitment

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  •   2011/08/31
  •   273
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional 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

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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

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Addresses

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    • European Association of Urology Research Foundation
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    • EAU Research Foundation
    • Peter FA Mulders, Prof. PhD, MD 
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    • EAU Research Foundation
    • Peter FA Mulders, Prof. PhD, MD 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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    •   [---]*
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Status

  •   Recruiting complete, follow-up continuing
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Trial Publications, Results and other Documents

  •   European Association of Urology
  •   MAGNOLIA Trial Website
  •   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.; 24268503
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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   5
  •   2016/01/14


* This entry means the parameter is not applicable or has not been set.