Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer
Conditions
Keywords
anterior urethral cancer, localized transitional cell cancer of the renal pelvis and ureter, posterior urethral cancer, stage II bladder cancer, stage III bladder cancer, transitional cell carcinoma of the bladder, urethral cancer associated with invasive bladder cancer, regional transitional cell cancer of the renal pelvis and ureter
Brief summary
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 and decrease the need for surgery. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by observation or surgery to remove the bladder (cystectomy) in treating patients who have stage II or stage III cancer of the urothelium.
Detailed description
OBJECTIVES: * Determine the pathologic complete response of patients with stage II or III transitional cell cancer of the urothelium treated with neoadjuvant gemcitabine, paclitaxel, and carboplatin followed by observation or immediate cystectomy. * Determine, preliminarily, if molecular markers predict response, survival, and tumor recurrence in patients treated with these regimens. * Determine recurrence rates and cystectomy-free survival of patients who choose observation after an initial response to neoadjuvant chemotherapy. * Compare the survival of patients treated with neoadjuvant chemotherapy followed by cystectomy vs observation. * Determine the feasibility, tolerability, and toxicity of these regimens in these patients. OUTLINE: This is a multicenter study. Patients receive gemcitabine IV over 30 minutes and paclitaxel IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks after completion of neoadjuvant chemotherapy, patients undergo a third transurethral resection of bladder tumor. Patients with T0 disease after neoadjuvant chemotherapy may choose to undergo observation. These patients undergo cystoscopies with biopsies every 3 months for 1 year, every 4 months for 1 year, and then every 6 months until disease progression. Patients with T1 disease or greater after neoadjuvant chemotherapy undergo immediate cystectomy. Patients with T0 disease may also choose this option. Patients undergoing immediate cystectomy are followed every 6 months for 2 years and then annually for 3 years. PROJECTED ACCRUAL: A total of 95 patients will be accrued for this study within 2 years.
Interventions
DRUGcarboplatin
DRUGgemcitabine
DRUGpaclitaxel
PROCEDUREsurgery
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed muscle-invasive (T2-T4a), node-negative (N0) urothelial transitional cell cancer (TCC) of the bladder * Focal squamous and/or adenocarcinoma differentiation, defined as ≤ 10% of tumor volume allowed * The following diagnoses are not allowed: * Small cell carcinoma * Sarcomatoid components * Disease diagnosed with an initial transurethral resection of bladder tumor (TURBT) and a second TURBT performed within 8 weeks of first with attempt to remove all tumor present * Residual disease after second TURBT allowed * No more than 14-56 days after second TURBT * No metastatic disease by chest x-ray and CT scan or MRI of the abdomen and pelvis * Fresh tumor tissue, paraffin tumor tissue, unstained slides, or cell block specimen from one or both TURBTs available PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * White blood cell count (WBC) at least 3,500/mm\^3 * Absolute granulocyte count at least 1,500/mm\^3 * Platelet count at least lower limit of normal Hepatic * Bilirubin no greater than 1.5 mg/dL * Aspartate aminotransferase (SGOT) no greater than 2 times upper limit of normal Renal * Creatinine no greater than 2.0 mg/dL AND/OR * Creatinine clearance at least 60 mL/min Other * No prohibitive medical risk that would preclude radical cystectomy * No other serious concurrent systemic disorder that would preclude study compliance * No other malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer in complete remission, or any other cancer for which patient has been disease-free for 5 years * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * Prior intravesical immunotherapy allowed Chemotherapy * No prior systemic chemotherapy for TCC of the urothelium * Prior intravesical chemotherapy allowed Endocrine therapy * Not specified Radiotherapy * No prior radiotherapy for TCC of the urothelium * No concurrent radiotherapy Surgery * See Disease Characteristics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy | up to 12 weeks after registration (assessed within 8 weeks after completion of 3 cycles of chemotherapy ) | Pathologic complete response (CR) is defined as absence of viable tumor in the TURBT specimen. Stable/No Response is defined as at least some disease evaluation tests were done (same tests as baseline) and status does not qualify for CR or Progression. Progression is defined as one or more of the following must occur: unequivocal progression of disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without documented progression or symptomatic deterioration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 0-2 years | Overall survival is defined from the date of registration to date of death from any cause |
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Patients were assessed for adverse events at weeks 1, 2, 4, 5, 7, 8, and following surgery | Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery Patients receive 3 cycles (1 cycle = 21 days) of neoadjuvant chemotherapy (800 mg/m\^2 of gemcitabine IV and 80 mg/m\^2 of Paclitaxel IV on days 1 and 8 and Carboplatin IV on day 1), TURBT within 4-8 weeks of chemotherapy, option of proceeding with immediate cystectomy or observation. | 74 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Ineligible | 2 |
| Overall Study | Progression/relapse | 1 |
| Overall Study | Refusal unrelated to adverse event | 1 |
Baseline characteristics
| Characteristic | Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery |
|---|---|
| Age Continuous | 69 years |
| Clinical T Stage T2 | 52 participants |
| Clinical T Stage T3 | 17 participants |
| Clinical T Stage T4a | 5 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 16 Participants |
| Performance Status 0 | 50 participants |
| Performance Status 1 | 16 participants |
| Performance Status Missing | 8 participants |
| Prior Intravesical Therapy Missing | 4 participants |
| Prior Intravesical Therapy No | 59 participants |
| Prior Intravesical Therapy Yes | 11 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 70 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 73 / 74 |
| serious Total, serious adverse events | 2 / 74 |
Outcome results
Primary
Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy
Pathologic complete response (CR) is defined as absence of viable tumor in the TURBT specimen. Stable/No Response is defined as at least some disease evaluation tests were done (same tests as baseline) and status does not qualify for CR or Progression. Progression is defined as one or more of the following must occur: unequivocal progression of disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without documented progression or symptomatic deterioration.
Time frame: up to 12 weeks after registration (assessed within 8 weeks after completion of 3 cycles of chemotherapy )
Population: All eligible patients who started treatment were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy | 46 percentage of participants |
Secondary
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time frame: Patients were assessed for adverse events at weeks 1, 2, 4, 5, 7, 8, and following surgery
Population: Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Melena/ GI bleeding | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Neutropenia/granulocytopenia | 41 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | SGPT (ALT) increase | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Abnormal troponin I (cTnI) | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Allergic reaction | 2 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Anemia | 5 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Bilirubin increase | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Cardiac ischemia/infarction | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Creatinine increase | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Diarrhea without colostomy | 2 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Duodenal ulcer | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Dyspnea | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Fatigue/malaise/lethargy | 3 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Febrile neutropenia | 2 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | GI-other | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Hemolysis | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Incontinence | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Infection with 3-4 neutropenia | 2 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Infection, unk ANC | 2 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Leukopenia | 22 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Lymphopenia | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Thrombocytopenia | 13 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Ureteral obstruction | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Urinary tr infect w/ neutrop | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Urinary tr infect w/o neutrop | 1 Participants |
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Vomiting | 1 Participants |
Secondary
Overall Survival (OS)
Overall survival is defined from the date of registration to date of death from any cause
Time frame: 0-2 years
Population: All eligible patients who started treatment were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery | Overall Survival (OS) | 59 percentage of participants |