Safety and Efficacy Study of MAGE-A3 + AS-15 in Patients With Muscle-invasive Bladder Cancer After Cystectomy
Condition: Urinary Bladder Neoplasms
MeSH terms: Urinary Bladder Neoplasms
Intervention: recMAGE-A3 + AS15 ASCI; Placebo
Intervention description: 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; 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 83.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urinary Bladder neoplasms; Lymphoproliferative Disorders; Immune System Diseases; Cystectomy; Adjuvants, Immunologic; Immunologic Factors

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.
    

Eligibility 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