A Phase 3 interventional study of cisplatin and doxorubicin hydrochloride in Bladder Cancer, sponsored by SWOG Cancer Research Network. Terminated at 74 sites in 2 countries. Open to participants aged Up to 120 Years. Per ClinicalTrials.gov, last updated 2017-06-08.
Sponsored by SWOG Cancer Research Network · Phase 3, Interventional, and Treatment
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective than observation alone in treating bladder cancer.
PURPOSE: This randomized phase III trial is studying combination chemotherapy to see how well it works compared to observation alone in treating patients with bladder cancer.
OBJECTIVES:
OUTLINE: This is a randomized, multicenter study. Patients are assigned to 1 of 2 treatment groups based on the status of the p53 gene in the bladder tumor.
Group A (p53 gene alteration, defined by greater than 10% nuclear reactivity): Patients are stratified according to age (under 65 vs 65 and over), stage (P1 vs P2a vs P2b), grade (1 or 2 vs 3 or 4), and p21 status. Patients are randomized to 1 of 2 treatment arms within 10 weeks after radical cystectomy and bilateral pelvic lymphadenectomy and within 2 weeks after registration.
Patients who are eligible for randomization but decline to be randomized undergo observation for recurrence.
Patients are followed every 6 months for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 800 patients will be accrued for this study within 4.75 years.
1,649 studies on the registry are indexed under Urinary Bladder Neoplasms; 427 are open to participants now.
This study's enrollment of 521 is above the median of 60 across 1,183 interventional studies indexed under Urinary Bladder Neoplasms.
Browse Urinary Bladder Neoplasms studies →SWOG Cancer Research Network is the lead sponsor of 339 studies on the registry; 37 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Histologically proven organ confined transitional cell carcinoma (TCC) of the bladder
Must have undergone radical cystectomy and bilateral pelvic lymphadenectomy with pathologic stage from definitive cystectomy specimen of P1, P2a, or P2b and N0, M0 TCC with or without squamous/glandular differentiation (no adenocarcinoma, squamous cell carcinoma, or small cell carcinoma)
Eligible for randomization if:
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
Randomization group:
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Randomization group:
Endocrine therapy
Radiotherapy
Surgery
Patients with altered (+) p53, reconsented to randomization, randomized to three cycles of MVAC
Drug: cisplatin · Drug: doxorubicin hydrochloride · Drug: methotrexate · Drug: vinblastine
Patients with altered (+) p53, reconsented to randomization, randomized to observation
Patients with unaltered (-) p53
Patients with altered (+) p53, patients did not consent to randomization
Probability of Recurring
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.
Time frame: 5 years
Probability of Overall Survival
p53 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.
Time frame: 5 years
Probability of Recurrence
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.
Time frame: 5 years
Probability of Overall Survival
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.
Time frame: 5 years
| Milestone | Arm I: M-VAC x 3 | Arm II: Observation | Arm III: Observation | Arm IV: Observation |
|---|---|---|---|---|
| Started | 58 | 56 | 227 | 158 |
| Completed | 39 | 56 | 227 | 158 |
| Not completed | 19 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 12 | 0 | 0 | 0 |
| Withdrew: Adverse event | 5 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 | 0 | 0 |
| Withdrew: Lack of efficacy | 1 | 0 | 0 | 0 |
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.
| probability | Arm I: M-VAC x 3 | Arm II: Observation |
|---|---|---|
| Probability of Recurring | 0.85 ± 0.05 | 0.84 ± 0.06 |
p53 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.
| probability | Arm I: M-VAC x 3 | Arm II: Observation |
|---|---|---|
| Probability of Overall Survival | 0.87 ± 0.05 | 0.84 ± 0.05 |
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.
| probability | p53 Positive Patients | p53 Negative Patients |
|---|---|---|
| Probability of Recurrence | 0.83 ± 0.03 | 0.77 ± 0.03 |
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.
| probability | p53 Positive Patients | p53 Negative Patients |
|---|---|---|
| Probability of Overall Survival | 0.82 ± 0.03 | 0.84 ± 0.03 |
Collected over 5 years: every 3 months for the first year, every 6 months for the following 4 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I: M-VAC x 3 | 12/58 (20.7%) | 0/46 (0%) | 35/46 (76.1%) |
| Arm II: Observation | 9/56 (16.1%) | — | — |
| Arm III: Observation | 41/227 (18.1%) | — | — |
| Arm IV: Observation | 36/158 (22.8%) | — | — |
| Event | Arm I: M-VAC x 3 | Arm II: Observation | Arm III: Observation | Arm IV: Observation |
|---|---|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 31/46 | — | — | — |
| Decreased WBCBlood and lymphatic system disorders | 14/46 | — | — | — |
| FatigueGeneral disorders | 6/46 | — | — | — |
| NauseaGastrointestinal disorders | 6/46 | — | — | — |
| StomatitisGastrointestinal disorders | 5/46 | — | — | — |
| VomitingGastrointestinal disorders | 5/46 | — | — | — |
| LymphopeniaBlood and lymphatic system disorders | 4/46 | — | — | — |
| Age, Categorical(Participants) | Arm I: M-VAC x 3 | Arm II: Observation | Arm III: Observation | Arm IV: Observation | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 37 | 41 | 127 | 81 | 286 |
| >=65 years | 21 | 15 | 100 | 77 | 213 |
| Sex: Female, Male(Participants) | Arm I: M-VAC x 3 | Arm II: Observation | Arm III: Observation | Arm IV: Observation | Total |
|---|---|---|---|---|---|
| Female | 7 | 9 | 49 | 34 | 99 |
| Male | 51 | 47 | 178 | 124 | 400 |
| Race/Ethnicity, Customized(Participants) | Arm I: M-VAC x 3 | Arm II: Observation | Arm III: Observation | Arm IV: Observation | Total |
|---|---|---|---|---|---|
| White | 52 | 49 | 203 | 150 | 454 |
| Black | 4 | 1 | 13 | 4 | 22 |
| Asian | 0 | 2 | 6 | 1 | 9 |
| Hispanic | 1 | 4 | 3 | 3 | 11 |
| Other | 1 | 0 | 2 | 0 | 3 |
| Stage(Participants) | Arm I: M-VAC x 3 | Arm II: Observation | Arm III: Observation | Arm IV: Observation | Total |
|---|---|---|---|---|---|
| pT1 | 21 | 16 | 87 | 61 | 185 |
| pT2 and pT2a | 37 | 40 | 140 | 97 | 314 |
| Grade(Participants) | Arm I: M-VAC x 3 | Arm II: Observation | Arm III: Observation | Arm IV: Observation | Total |
|---|---|---|---|---|---|
| 1 or 2 | 2 | 1 | 16 | 5 | 24 |
| 3 or 4 | 56 | 55 | 210 | 152 | 473 |
| missing | 0 | 0 | 1 | 1 | 2 |
| No. of nodes identified(Participants) | Arm I: M-VAC x 3 | Arm II: Observation | Arm III: Observation | Arm IV: Observation | Total |
|---|---|---|---|---|---|
| <15 nodes | 22 | 14 | 68 | 64 | 168 |
| >= 15 nodes | 36 | 42 | 159 | 94 | 331 |
| p21 status(Participants) | Arm I: M-VAC x 3 | Arm II: Observation | Arm III: Observation | Arm IV: Observation | Total |
|---|---|---|---|---|---|
| Absent | 24 | 22 | 35 | 64 | 145 |
| Present | 34 | 34 | 190 | 92 | 350 |
| missing | 0 | 0 | 2 | 2 | 4 |
| Lymphovascular invasion(Participants) | Arm I: M-VAC x 3 | Arm II: Observation | Arm III: Observation | Arm IV: Observation | Total |
|---|---|---|---|---|---|
| No | 33 | 25 | 117 | 84 | 259 |
| Yes | 13 | 14 | 46 | 29 | 102 |
| Unknown | 12 | 17 | 64 | 45 | 138 |
1 further baseline measures are reported on the registry.
Ran from Aug 1997 to primary completion in Mar 2011, 163 months.
Results were first posted in Jun 2017, 6 years 3 months after primary completion.
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This study is terminated, as verified in May 2017. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Cisplatin · Methotrexate · Vinblastine
SWOG Cancer Research Network →