Trial Outcomes & Findings for 4B951, Combination Chemotherapy in Treating Patients With Bladder Cancer (NCT NCT00005047)
NCT ID: NCT00005047
Last Updated: 2017-06-08
Results Overview
p53 positive patients randomized to MVAC (arm I) compared to p53 positive patients randomized to observation (arm II). Time from registration to the first observation of disease recurrence, censoring patients who died of unrelated causes. Probabilities of recurring were based on cumulative incidence curves. Recurrence is defined as first radiological appearance of bladder cancer, per local standard of care.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
521 participants
Primary outcome timeframe
5 years
Results posted on
2017-06-08
Participant Flow
Patients with stage pT1/T2N0M0 urothelial cancer who had undergone a radical cystectomy within the prior 9 weeks were eligible for enrollment. Twenty-two patients who were registered were never assigned to a group after enrolling due to: missing baseline documentation (5), incorrect disease stage (13), and patient withdrawal (4).
Participant milestones
| Measure |
Arm I: M-VAC x 3
Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC
cisplatin
doxorubicin hydrochloride
methotrexate
vinblastine
|
Arm II: Observation
Patients with altered (+) p53, reconsented to randomization, randomized to observation
|
Arm III: Observation
Patients with unaltered (-) p53
|
Arm IV: Observation
Patients with altered (+) p53, patients did not consent to randomization
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
58
|
56
|
227
|
158
|
|
Overall Study
COMPLETED
|
39
|
56
|
227
|
158
|
|
Overall Study
NOT COMPLETED
|
19
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Arm I: M-VAC x 3
Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC
cisplatin
doxorubicin hydrochloride
methotrexate
vinblastine
|
Arm II: Observation
Patients with altered (+) p53, reconsented to randomization, randomized to observation
|
Arm III: Observation
Patients with unaltered (-) p53
|
Arm IV: Observation
Patients with altered (+) p53, patients did not consent to randomization
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
12
|
0
|
0
|
0
|
|
Overall Study
Adverse Event
|
5
|
0
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
0
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
0
|
0
|
Baseline Characteristics
4B951, Combination Chemotherapy in Treating Patients With Bladder Cancer
Baseline characteristics by cohort
| Measure |
Arm I: M-VAC x 3
n=58 Participants
p53 positive, randomized to 3 cycles of adjuvant combination methotrexate, vinblastine, doxorubicin and cisplatin (MVAC)
|
Arm II: Observation
n=56 Participants
p53 positive, randomized to observation/no intervention
|
Arm III: Observation
n=227 Participants
p53 negative, assigned to observation/no intervention
|
Arm IV: Observation
n=158 Participants
p53 positive, refused random assignment, assigned to observation/no intervention
|
Total
n=499 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
37 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
127 Participants
n=5 Participants
|
81 Participants
n=4 Participants
|
286 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
21 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
77 Participants
n=4 Participants
|
213 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
99 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
51 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
178 Participants
n=5 Participants
|
124 Participants
n=4 Participants
|
400 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
52 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
203 Participants
n=5 Participants
|
150 Participants
n=4 Participants
|
454 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Stage
pT1
|
21 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
61 Participants
n=4 Participants
|
185 Participants
n=21 Participants
|
|
Stage
pT2 and pT2a
|
37 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
97 Participants
n=4 Participants
|
314 Participants
n=21 Participants
|
|
Grade
1 or 2
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Grade
3 or 4
|
56 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
210 Participants
n=5 Participants
|
152 Participants
n=4 Participants
|
473 Participants
n=21 Participants
|
|
Grade
missing
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
No. of nodes identified
<15 nodes
|
22 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
64 Participants
n=4 Participants
|
168 Participants
n=21 Participants
|
|
No. of nodes identified
>= 15 nodes
|
36 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
159 Participants
n=5 Participants
|
94 Participants
n=4 Participants
|
331 Participants
n=21 Participants
|
|
p21 status
Absent
|
24 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
64 Participants
n=4 Participants
|
145 Participants
n=21 Participants
|
|
p21 status
Present
|
34 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
190 Participants
n=5 Participants
|
92 Participants
n=4 Participants
|
350 Participants
n=21 Participants
|
|
p21 status
missing
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Lymphovascular invasion
No
|
33 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
117 Participants
n=5 Participants
|
84 Participants
n=4 Participants
|
259 Participants
n=21 Participants
|
|
Lymphovascular invasion
Yes
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
102 Participants
n=21 Participants
|
|
Lymphovascular invasion
Unknown
|
12 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
138 Participants
n=21 Participants
|
|
Bladder carcinoma in situ
No
|
16 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
36 Participants
n=4 Participants
|
124 Participants
n=21 Participants
|
|
Bladder carcinoma in situ
Yes
|
34 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
137 Participants
n=5 Participants
|
99 Participants
n=4 Participants
|
302 Participants
n=21 Participants
|
|
Bladder carcinoma in situ
Unknown
|
8 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
73 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 5 yearsp53 positive patients randomized to MVAC (arm I) compared to p53 positive patients randomized to observation (arm II). Time from registration to the first observation of disease recurrence, censoring patients who died of unrelated causes. Probabilities of recurring were based on cumulative incidence curves. Recurrence is defined as first radiological appearance of bladder cancer, per local standard of care.
Outcome measures
| Measure |
Arm I: M-VAC x 3
n=58 Participants
Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC
cisplatin
doxorubicin hydrochloride
methotrexate
vinblastine
|
Arm II: Observation
n=56 Participants
Patients with altered (+) p53, reconsented to randomization, randomized to observation
|
|---|---|---|
|
Probability of Recurring
|
0.85 probability
Standard Error 0.05
|
0.84 probability
Standard Error 0.06
|
SECONDARY outcome
Timeframe: 5 yearsp53 positive patients randomized to MVAC (arm I) compared to p53 positive patients randomized to observation (arm II). Survival is calculated from registration to death due to any cause. Probabilities of survival were based on the Kaplan-Meier product-limit method.
Outcome measures
| Measure |
Arm I: M-VAC x 3
n=58 Participants
Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC
cisplatin
doxorubicin hydrochloride
methotrexate
vinblastine
|
Arm II: Observation
n=56 Participants
Patients with altered (+) p53, reconsented to randomization, randomized to observation
|
|---|---|---|
|
Probability of Overall Survival
|
0.87 probability
Standard Error 0.05
|
0.84 probability
Standard Error 0.05
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: This analysis compares p53 positive patients (combined arms I, II, and IV) to p53 negative patients (arm III).
Patients with tumors demonstrating alteration in p53 compared to patients with no p53 alterations. Probabilities of recurring were based on cumulative incidence curves. Recurrence is defined as first radiological appearance of bladder cancer, per local standard of care.
Outcome measures
| Measure |
Arm I: M-VAC x 3
n=272 Participants
Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC
cisplatin
doxorubicin hydrochloride
methotrexate
vinblastine
|
Arm II: Observation
n=227 Participants
Patients with altered (+) p53, reconsented to randomization, randomized to observation
|
|---|---|---|
|
Probability of Recurrence
|
0.83 probability
Standard Error 0.03
|
0.77 probability
Standard Error 0.03
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: This analysis compares p53 positive patients (combined arms I, II, and IV) to p53 negative patients (arm III).
Patients with tumors demonstrating alteration in p53 compared to patients with no p53 alterations. Probabilities of survival were based on the Kaplan-Meier product-limit method.
Outcome measures
| Measure |
Arm I: M-VAC x 3
n=272 Participants
Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC
cisplatin
doxorubicin hydrochloride
methotrexate
vinblastine
|
Arm II: Observation
n=227 Participants
Patients with altered (+) p53, reconsented to randomization, randomized to observation
|
|---|---|---|
|
Probability of Overall Survival
|
0.82 probability
Standard Error 0.03
|
0.84 probability
Standard Error 0.03
|
Adverse Events
Arm I: M-VAC x 3
Serious events: 0 serious events
Other events: 35 other events
Deaths: 12 deaths
Arm II: Observation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 9 deaths
Arm III: Observation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 41 deaths
Arm IV: Observation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 36 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm I: M-VAC x 3
n=46 participants at risk
Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC
cisplatin
doxorubicin hydrochloride
methotrexate
vinblastine
|
Arm II: Observation
Patients with altered (+) p53, reconsented to randomization, randomized to observation
|
Arm III: Observation
Patients with unaltered (-) p53
|
Arm IV: Observation
Patients with altered (+) p53, patients did not consent to randomization
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Decreased WBC
|
30.4%
14/46 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
|
General disorders
Fatigue
|
13.0%
6/46 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
8.7%
4/46 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
|
Gastrointestinal disorders
Nausea
|
13.0%
6/46 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
|
Blood and lymphatic system disorders
Neutropenia
|
67.4%
31/46 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
|
Gastrointestinal disorders
Stomatitis
|
10.9%
5/46 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
|
Gastrointestinal disorders
Vomiting
|
10.9%
5/46 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
—
0/0 • 5 years: every 3 months for the first year, every 6 months for the following 4 years
Serious Adverse Events and Other Adverse events were recorded only for Arm I, as all other arms were observation. Adverse events were only recorded for those patients who received MVAC (46/58). All-Cause Mortality was monitored for patients in all the Arms.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place