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
1. Aged greater than or equal to 18 years at the time ICF is signed, either sex.
2. Histologically confirmed (after cystectomy) transitional cell carcinoma of bladder
urothelium which is MAGE-A3 positive.
3. Written informed consent for tissue and (optional) urine sampling, MAGE-A3 expression
analysis and gene profiling and optional translational research has been obtained
from the patient prior to cystectomy, and written informed consent for the complete
study has been obtained prior to the performance of any other protocol-specific
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. (TNM classification)
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 9 weeks prior to randomization. Other
examinations should be performed as clinically indicated.
6. Patient is fully recovered from surgery within 9 weeks following cystectomy.
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
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.
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, or neo-adjuvant 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
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. 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) or uncontrolled arrhythmia.
13. The patient uses alternative treatments eg. plantextracts.