Bladder Cancer
Conditions
Keywords
recurrent bladder cancer, stage 0 bladder cancer, stage I bladder cancer, transitional cell carcinoma of the bladder
Brief summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gemcitabine directly into the bladder may kill more tumor cells. PURPOSE: This phase II trial is studying how well gemcitabine works in treating patients with recurrent bladder cancer that has progressed despite previous Bacillus Calmette-Guerin (BCG).
Detailed description
OBJECTIVES: * Determine the 8-12 week efficacy of intravesical gemcitabine, in terms of complete response rate, in patients with recurrent superficial transitional cell carcinoma of the bladder that have progressed despite prior intravesical Bacillus Calmette-Guerin (BCG). * Determine the recurrence-free, worsening-free, progression-free, and overall survival of patients treated with this drug. * Evaluate the toxicity of this drug in these patients. * Correlate, preliminarily, expression levels of genes or genetic polymorphisms involved in the gemcitabine pathway and angiogenesis with clinical toxicity, response, and relapse-free survival of patients treated with this drug. OUTLINE: This is a multicenter study. * Induction therapy: Patients receive gemcitabine intravesically once a week for 6 weeks (weeks 1-6) in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response proceed to maintenance therapy at week 14. * Maintenance therapy: Patients receive gemcitabine intravesically once in weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 25-45 patients will be accrued for this study within 6-12 months.
Interventions
DRUGgemcitabine hydrochloride
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 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed superficial transitional cell carcinoma (TCC) of the bladder meeting 1 of the following stage criteria: * Stage T1, grade 2-3 * Stage Tis * Stage Ta, grade 3-4 or multifocal (\> 2 lesions) * Must have received and failed ≥ 2 courses of intravesical Bacillus Calmette-Guerin (BCG) (one 6-week course, plus one 3-week course, or fewer weeks if BCG was discontinued due to side effects) within the past 3 years * Recurrent disease * Must have had a transurethral resection of the bladder tumor (TURBT) or bladder biopsy within the past 60 days documenting tumor recurrence and tumor stage and grade * TURBT or biopsy must have been performed ≥ 6 weeks after the completion of BCG and/or other immunotherapy treatment (or ≥ 14 days after completion of intravesical chemotherapy treatment) * All visible tumor must have been resected at the time of the last biopsy * No evidence of urethral or renal pelvis TCC by upper tract radiological imaging (e.g., intravenous pyelogram, CT urogram, or retrograde pyelogram) within the past 2 years PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Other * Not pregnant or nursing * Fertile patients must use effective contraception * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * Prior intravesical interferon alfa allowed, alone or in combination with Bacillus Calmette-Guerin (BCG) Chemotherapy * See Disease Characteristics * No more than 1 course of intravesical chemotherapy (e.g., thiotepa, mitomycin, or doxorubicin) within the past year, defined as 6 or more weekly instillations, with or without monthly maintenance instillations * No prior gemcitabine Endocrine therapy * Not specified Radiotherapy * No prior pelvic radiotherapy * No concurrent radiotherapy to any other area of the body Surgery * See Disease Characteristics * Recovered from prior surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate at the End of Induction | Week 8-12, then every 3 months for the first 2 years, and then every 6 months for the years 3-5 | Complete Response is defined as negative cystoscopy with negative biopsy and no evidence of cancer on urine cytology at the Week 8 - 12 cystoscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 1 year | Measured from the day of registration to death due to any cause. Survival is censored at date of last contact. |
| Recurrence-free Survival (RFS) | 1 year | Recurrence-free Survival is defined as time from registration to first instance of disease recurrence, or death due to 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 weekly for 6 weeks and then every 4 weeks for 40 weeks | Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. 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 |
|---|---|
| Intravesical Gemcitabine Patients receive induction treatment with instillations of 2 gm gemcitabine dissolved in 100 cc normal saline weekly for 6 weeks. Beginning at week 14, patients achieving a complete response (CR) after induction go onto maintenance and are treated with one intravesical gemcitabine every 4 weeks for 40 weeks. | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Ineligible | 9 |
| Overall Study | No Protocol Treatment Received | 2 |
| Overall Study | Other - Not Protocol Specified | 3 |
| Overall Study | Progression/relapse | 34 |
Baseline characteristics
| Characteristic | Intravesical Gemcitabine |
|---|---|
| Age, Continuous | 70 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 43 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 47 |
| serious Total, serious adverse events | 0 / 47 |
Outcome results
Primary
Complete Response Rate at the End of Induction
Complete Response is defined as negative cystoscopy with negative biopsy and no evidence of cancer on urine cytology at the Week 8 - 12 cystoscopy
Time frame: Week 8-12, then every 3 months for the first 2 years, and then every 6 months for the years 3-5
Population: All eligible patients who started treatment were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intravesical Gemcitabine | Complete Response Rate at the End of Induction | 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 3.0. 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 weekly for 6 weeks and then every 4 weeks for 40 weeks
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) |
|---|---|---|---|
| Intravesical Gemcitabine | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Neutrophils/granulocytes (ANC/AGC) | 1 Participants |
| Intravesical Gemcitabine | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Pain - Bladder | 1 Participants |
| Intravesical Gemcitabine | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Urinary frequency/urgency | 2 Participants |
Secondary
Overall Survival (OS)
Measured from the day of registration to death due to any cause. Survival is censored at date of last contact.
Time frame: 1 year
Population: All eligible patients who started treatment were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intravesical Gemcitabine | Overall Survival (OS) | 98 percentage of participants |
Secondary
Recurrence-free Survival (RFS)
Recurrence-free Survival is defined as time from registration to first instance of disease recurrence, or death due to any cause.
Time frame: 1 year
Population: All eligible patients who started treatment were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intravesical Gemcitabine | Recurrence-free Survival (RFS) | 28 percentage of participants |