Urinary Bladder Neoplasms
Conditions
Keywords
Urothelial Cancer, Bladder Cancer, Metastatic
Brief summary
This trial is for people with bladder cancer that has spread. The purpose of this research study is to see if the chemotherapy combination of gemcitabine and cisplatin plus paclitaxel is safe and effective treatment for bladder cancer. Paclitaxel, gemcitabine and cisplatin have all been approved by the United States Food and Drug Administration (FDA). Gemcitabine and cisplatin is a standard treatment for bladder cancer. There have been studies that show that paclitaxel and cisplatin have antitumor activity in bladder cancer. European researchers studied paclitaxel, gemcitabine and cisplatin (same drug combination in this trial) and found that the combination provided good disease control and was well tolerated. Investigators are studying the same drug combination, but at different dosages and schedule.
Detailed description
The rationale of the present study is to develop a combination based on the pharmacokinetics and mechanisms of action of the agents paclitaxel plus gemcitabine and cisplatin, which are all known active agents in urothelial tumors. Gemcitabine may be synergistic with DNA-damaging drugs such as paclitaxel and cisplatin because it can antagonize DNA repair. Investigators will investigate the combination in this Phase II study.
Interventions
DRUGPaclitaxel
175 mg/m2 will be administered as an IVPB over 3 hours on Day 2 of each cycle (each cycle is 21 days).
DRUGGemcitabine
1000 mg/m2 will be administered as an IV infusion over 10 mg/minute on Days 1 and 8 of each cycle (each cycle is 21 days).
DRUGCisplatin
70 mg/m2 will be administered as an IVPB over 2 hours on Day 2 of each cycle (each cycle is 21 days).
Sponsors
The University of Texas Health Science Center, Houston
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
* All patients must have histologic demonstration of metastatic or locally unresectable transitional cell carcinoma of the urothelium. Minor components (\<50% overall) of variants such as glandular or squamous differentiation, or evolution to more aggressive phenotypes, such as sarcomatoid, or small cell changes are acceptable. However, when these atypical histologies are dominant, other treatment approaches may be more appropriate, and such patients are not eligible. * All patients must have measurable or evaluable disease. In general, liver and lung lesions should be at least 1 cm, and patients with node-only disease should have lesions of ≥ 1.5 cm in the largest dimension. Patients with disease confined to bone may be eligible if a measurable lytic defect is present. Patients with a 3-dimensional mass or pelvic sidewall fixation on bladder examination under anesthesia are considered to have measurable disease. * All patients must have adequate physiologic reserves as evidenced by: * Life expectancy of at least 12 weeks. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. * No clinical history of heart disease and a normal EKG or an ejection fraction measured by echocardiogram or MUGA scan of at least 45%. * Transaminase less than twice the upper limit of normal. Bilirubin \<1.5 mg%. * Serum creatinine ≤2.0 mg/dL. Patients presenting with obstructive uropathy may be eligible if they show excellent response to nephrostomy drainage. * Absolute neutrophil count ≥1500; platelet count ≥100,000. * Patients must not have had any previous systemic chemotherapy for bladder cancer, including neoadjuvant or adjuvant treatment given remotely. Gemcitabine/cisplatin is the standard of care for metastatic urothelial cancer. Patients who have received treatment would be either resistant or refractory to additional doses. In addition, they would have residual adverse effects from treatment and would be particularly susceptible to further neuropathic adverse events. Any prior intravesicular therapy is allowed. * Women of childbearing potential must have a negative pregnancy test prior to starting therapy. Men and women of childbearing potential must be willing to consent using effective contraceptive while on treatment and for a reasonable period thereafter. * Patients must not have an active, or likely to become active, second malignancy. * Patients must be at least 6 weeks out from pelvic irradiation, and must not have had more than 10% of the bone marrow irradiated.
Exclusion criteria
* Patients with uncontrolled CNS metastasis are not eligible. * Patients with a history of peripheral neuropathy greater than grade 1 are not eligible. * Pregnant women are excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy as Measured by the Objective Response Rate (ORR). | From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 6 months | Objective Response Rate (ORR) is defined as the proportion of patients achieving either a complete response or a partial response based on imaging at any time during the study. Complete response or partial response is based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Drug Regimen as Measured by Number of Adverse Events | From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 6 months | Toxicity assessment will be observational. Numbers and types of events will be quantified and graded according to CTCAE. |
| Efficacy as Measured by Number Who Progressed | From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 6 months | Progression is defined using RECIST 1.1 criteria: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Combination Chemotherapy Combination chemotherapy consisting of gemcitabine and cisplatin plus paclitaxel on a 21-day cycle.
Gemcitabine: 1000 mg/m2 will be administered as an IV infusion over 10 mg/minute on Days 1 and 8 of each cycle (each cycle is 21 days).
Paclitaxel: 175 mg/m2 will be administered as an IVPB over 3 hours on Day 2 of each cycle (each cycle is 21 days).
Cisplatin: 70 mg/m2 will be administered as an IVPB over 2 hours on Day 2 of each cycle (each cycle is 21 days). | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Combination Chemotherapy |
|---|---|
| Age, Continuous | 65 years |
| ECOG Performance Status ECOG score of 0 | 2 Participants |
| ECOG Performance Status ECOG score of 1 | 1 Participants |
| ECOG Performance Status ECOG score of 2 | 0 Participants |
| ECOG Performance Status ECOG score of 3 | 0 Participants |
| ECOG Performance Status ECOG score of 4 | 0 Participants |
| ECOG Performance Status ECOG score of 5 | 0 Participants |
| Race/Ethnicity, Customized African American | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 1 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 3 / 3 |
Outcome results
Primary
Efficacy as Measured by the Objective Response Rate (ORR).
Objective Response Rate (ORR) is defined as the proportion of patients achieving either a complete response or a partial response based on imaging at any time during the study. Complete response or partial response is based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination Chemotherapy | Efficacy as Measured by the Objective Response Rate (ORR). | 3 Participants |
Secondary
Efficacy as Measured by Number Who Progressed
Progression is defined using RECIST 1.1 criteria: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination Chemotherapy | Efficacy as Measured by Number Who Progressed | 1 Participants |
Secondary
Safety of Drug Regimen as Measured by Number of Adverse Events
Toxicity assessment will be observational. Numbers and types of events will be quantified and graded according to CTCAE.
Time frame: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Chemotherapy | Safety of Drug Regimen as Measured by Number of Adverse Events | 124 adverse event |