Trial Outcomes & Findings for Safety and Efficacy Study of MAGE-A3 + AS-15 in Patients With Muscle-invasive Bladder Cancer After Cystectomy (NCT NCT01435356)

Last Updated: 2019-01-09

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

83 participants

Primary outcome timeframe

5 years

Results posted on

2019-01-09

Participant Flow

83 patients were randomised, 52 for recMAGE-A3 +AS15 and 31 for placebo treatment. 6 patients did not start treatment due to ineligibility (4 for recMAGE-A3 +AS15 and 2 for placebo treatment).

Participant milestones

Participant milestones
Measure	recMage-A3 + AS15 ASCI MAGE A3 positive patients treated with recMAGE-A3 + AS15 ASCI 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 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
Overall Study STARTED	48	29
Overall Study COMPLETED	16	5
Overall Study NOT COMPLETED	32	24

Reasons for withdrawal

Reasons for withdrawal
Measure	recMage-A3 + AS15 ASCI MAGE A3 positive patients treated with recMAGE-A3 + AS15 ASCI 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 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
Overall Study Adverse Event	2	0
Overall Study Disease progression/recurrence	17	10
Overall Study Protocol Violation	0	1
Overall Study Study Discontinuation, amendment 4	5	11
Overall Study Withdrawal by Subject	1	1
Overall Study Facial palsy	1	0
Overall Study IC withdrawal due to study cancellation	1	0
Overall Study Physician Decision	1	0
Overall Study Patient decision	3	0
Overall Study Patient moved to another city	1	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	recMage-A3 + AS15 ASCI n=48 Participants MAGE A3 positive patients treated with recMAGE-A3 + AS15 ASCI 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 n=29 Participants 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	Total n=77 Participants Total of all reporting groups
Age, Continuous	65.7 years STANDARD_DEVIATION 8.4 • n=48 Participants	65.5 years STANDARD_DEVIATION 9.6 • n=29 Participants	65.6 years STANDARD_DEVIATION 8.8 • n=77 Participants
Sex: Female, Male Female	8 Participants n=48 Participants	8 Participants n=29 Participants	16 Participants n=77 Participants
Sex: Female, Male Male	40 Participants n=48 Participants	21 Participants n=29 Participants	61 Participants n=77 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Netherlands	4 participants n=48 Participants	7 participants n=29 Participants	11 participants n=77 Participants
Region of Enrollment Czechia	6 participants n=48 Participants	1 participants n=29 Participants	7 participants n=77 Participants
Region of Enrollment Poland	1 participants n=48 Participants	0 participants n=29 Participants	1 participants n=77 Participants
Region of Enrollment Italy	0 participants n=48 Participants	2 participants n=29 Participants	2 participants n=77 Participants
Region of Enrollment France	9 participants n=48 Participants	3 participants n=29 Participants	12 participants n=77 Participants
Region of Enrollment Germany	7 participants n=48 Participants	3 participants n=29 Participants	10 participants n=77 Participants
Region of Enrollment Russia	3 participants n=48 Participants	2 participants n=29 Participants	5 participants n=77 Participants
Region of Enrollment Spain	18 participants n=48 Participants	11 participants n=29 Participants	29 participants n=77 Participants
T-category of bladder cancer at diagnosis T2	22 Participants n=48 Participants • T2 (tumor invades muscle), T3 (tumor invades perivesical tissue), T4 (tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall).	13 Participants n=29 Participants • T2 (tumor invades muscle), T3 (tumor invades perivesical tissue), T4 (tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall).	35 Participants n=77 Participants • T2 (tumor invades muscle), T3 (tumor invades perivesical tissue), T4 (tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall).
T-category of bladder cancer at diagnosis T3	21 Participants n=48 Participants • T2 (tumor invades muscle), T3 (tumor invades perivesical tissue), T4 (tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall).	13 Participants n=29 Participants • T2 (tumor invades muscle), T3 (tumor invades perivesical tissue), T4 (tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall).	34 Participants n=77 Participants • T2 (tumor invades muscle), T3 (tumor invades perivesical tissue), T4 (tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall).
T-category of bladder cancer at diagnosis T4	5 Participants n=48 Participants • T2 (tumor invades muscle), T3 (tumor invades perivesical tissue), T4 (tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall).	3 Participants n=29 Participants • T2 (tumor invades muscle), T3 (tumor invades perivesical tissue), T4 (tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall).	8 Participants n=77 Participants • T2 (tumor invades muscle), T3 (tumor invades perivesical tissue), T4 (tumor invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall).
N-category classification of bladder cancer at diagnosis N0	36 Participants n=48 Participants	22 Participants n=29 Participants	58 Participants n=77 Participants
N-category classification of bladder cancer at diagnosis N1	7 Participants n=48 Participants	4 Participants n=29 Participants	11 Participants n=77 Participants
N-category classification of bladder cancer at diagnosis N2	5 Participants n=48 Participants	3 Participants n=29 Participants	8 Participants n=77 Participants
M-category of bladder cancer at diagnosis M0	48 Participants n=48 Participants	29 Participants n=29 Participants	77 Participants n=77 Participants
M-category of bladder cancer at diagnosis M1	0 Participants n=48 Participants	0 Participants n=29 Participants	0 Participants n=77 Participants
Dominant Histological Type transitional (urothelial) cell carcinoma	43 Participants n=48 Participants	29 Participants n=29 Participants	72 Participants n=77 Participants
Dominant Histological Type squamous cell carcinoma	3 Participants n=48 Participants	0 Participants n=29 Participants	3 Participants n=77 Participants
Dominant Histological Type adenocarcinoma	1 Participants n=48 Participants	0 Participants n=29 Participants	1 Participants n=77 Participants
Dominant Histological Type Not available	1 Participants n=48 Participants	0 Participants n=29 Participants	1 Participants n=77 Participants
Mean weight	73.5 kg STANDARD_DEVIATION 13.3 • n=48 Participants	75.1 kg STANDARD_DEVIATION 12.8 • n=29 Participants	74.1 kg STANDARD_DEVIATION 13.4 • n=77 Participants
Mean Height	172 cm STANDARD_DEVIATION 7.2 • n=48 Participants	169 cm STANDARD_DEVIATION 9.8 • n=29 Participants	171 cm STANDARD_DEVIATION 8.4 • n=77 Participants

PRIMARY outcome

Timeframe: 5 years

Outcome measures

Outcome measures
Measure	recMage-A3 + AS15 ASCI n=48 Participants MAGE A3 positive patients treated with recMAGE-A3 + AS15 ASCI 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 n=29 Participants 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
Disease Free Survival	27.5 months Interval 22.7 to 32.3	19.8 months Interval 15.7 to 23.9

SECONDARY outcome

Timeframe: 5 years

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.

Outcome measures

Outcome measures
Measure	recMage-A3 + AS15 ASCI n=48 Participants MAGE A3 positive patients treated with recMAGE-A3 + AS15 ASCI 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 n=29 Participants 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
Overall Survival	35.5 months Interval 32.1 to 38.8	24.1 months Interval 21.0 to 27.2

SECONDARY outcome

Timeframe: 5 years

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.

Outcome measures

Outcome measures
Measure	recMage-A3 + AS15 ASCI n=48 Participants MAGE A3 positive patients treated with recMAGE-A3 + AS15 ASCI 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 n=29 Participants 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
Disease-free Specific Survival	27.5 months Interval 22.7 to 32.3	19.8 months Interval 15.7 to 23.9

SECONDARY outcome

Timeframe: 5 years

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.

Outcome measures

Outcome measures
Measure	recMage-A3 + AS15 ASCI n=48 Participants MAGE A3 positive patients treated with recMAGE-A3 + AS15 ASCI 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 n=29 Participants 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
Distant Metastasis-free Survival	31.5 months Interval 27.2 to 35.9	21.4 months Interval 17.5 to 25.2

Adverse Events

recMage-A3 + AS15 ASCI

Serious events: 13 serious events

Other events: 30 other events

Deaths: 6 deaths

Placebo

Serious events: 5 serious events

Other events: 10 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	recMage-A3 + AS15 ASCI n=48 participants at risk MAGE A3 positive patients treated with recMAGE-A3 + AS15 ASCI 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 n=29 participants at risk 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
General disorders Influenza like illness	10.4% 5/48 • Number of events 25 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.	10.3% 3/29 • Number of events 6 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.
General disorders Injection site erythema	8.3% 4/48 • Number of events 22 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.	0.00% 0/29 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.
General disorders Injection site induration	6.2% 3/48 • Number of events 21 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.	0.00% 0/29 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.
General disorders Injection site pain	35.4% 17/48 • Number of events 54 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.	0.00% 0/29 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.
General disorders Pyrexia	29.2% 14/48 • Number of events 41 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.	13.8% 4/29 • Number of events 5 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.
Infections and infestations Urinary tract infection	20.8% 10/48 • Number of events 11 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.	17.2% 5/29 • Number of events 6 • Adverse event data were collected over a period of 5 years (between Informed Consent First Patient and Last Visit Last Patient). It was pre-specified in the Protocol that Foreseeable AEs and SAEs specifically related to the cystectomy prior to first study treatment administration will not be considered as "Adverse Events". It was left to the investigator to asses the relation between the (S)AEs and the cystectomy. Progression/recurrence of the tumor were recorded in the clinical assessments in the eCRF and not as SAE. Death due to a progressive disease were recorded on a specific form in the eCRF but not as a SAE.

Additional Information

Wim P.J. Witjes, MD, PhD Scientific and Clinical Research Director

EAU Research Foundation

Phone: +31 26 389 0677

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI submits the proposed publication to Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor shall have the right to remove from the proposed publication any information that is considered confidential and/or proprietary. Sponsor shall have the right to request an additional delay to the proposed disclosure of no more than ninety (90) days so as to allow Sponsor to preserve its intellectual property.
Publication restrictions are in place

Restriction type: OTHER