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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by European Association of Urology Research Foundation
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
European Association of Urology Research Foundation
ClinicalTrials.gov Identifier:
NCT01435356
First received: September 2, 2011
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Urinary Bladder Neoplasms
Biological: recMAGE-A3 + AS15 ASCI
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by European Association of Urology Research Foundation:

Primary Outcome Measures:
  • Disease free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    To characterize the tumor microenvironment and lymphocyte infiltration in the primary tumor and its recurrence lesions


Estimated Enrollment: 273
Study Start Date: August 2011
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: recMage-A3 + AS15 ASCI
MAGE A3 positive patients treated with recMAGE-A3 + AS15 ASCI
Biological: recMAGE-A3 + AS15 ASCI
5 doses will be 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 Comparator: Placebo Biological: Placebo
5 doses will be 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

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01435356

Contacts
Contact: Raymond G Schipper, PhD +31263890677 r.schipper@uroweb.org
Contact: Wim PJ Witjes, PhD, MD +31263890677 w.witjes@uroweb.org

  Show 50 Study Locations
Sponsors and Collaborators
European Association of Urology Research Foundation
GlaxoSmithKline
Investigators
Principal Investigator: Peter FA Mulders, Prof. PhD, MD EAU Research Foundation
  More Information

Additional Information:
Publications:
Responsible Party: European Association of Urology Research Foundation
ClinicalTrials.gov Identifier: NCT01435356     History of Changes
Other Study ID Numbers: EAU RF 2010-01, NTR2846, 2010-024355-85
Study First Received: September 2, 2011
Last Updated: May 22, 2014
Health Authority: Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee for the Protection of Personnes
France: Conseil National de l'Ordre des Médecins
Germany: Ethics Commission
Germany: Paul-Ehrlich-Institut
Italy: Ethics Committee
Netherlands: Ministry of Health, Welfare and Sport
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Ethics Committee
Poland: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: The Central Register of Clinical Trials
Romania: Ethics Committee
Romania: National Agency for Medicines and Medical Devices
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Ethics Committee
Ukraine: Ethics Committee

Keywords provided by European Association of Urology Research Foundation:
Urinary Bladder neoplasms
Lymphoproliferative Disorders
Immune System Diseases
Cystectomy
Adjuvants, Immunologic
Immunologic Factors

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014