Cancer, Myeloproliferative Disorder, Urothelial Carcinoma
Conditions
Keywords
Myeloproliferative Disorder, urinary bladder, Cancer, ureter, renal pelvis, chemotherapy
Brief summary
Gemcitabine and carboplatin are two standard chemotherapy drugs used to treat tumors of the urothelial tract. These drugs do not shrink tumors in all patients and when they do, it is generally for a limited amount of time. This has led scientists to look for different ways to treat cancer. New drugs have been developed to treat cancer that work differently than standard chemotherapy drugs. One new class of drugs are called 'angiogenesis-inhibitors'. These drugs attempt to decrease the blood supply to tumors. By doing so, this may limit the tumor's source of oxygen and nutrients and prevent the tumor from growing. Bevacizumab is an anti-angiogenic drug. In some other cancers such as colon cancer and lung cancer, combining bevacizumab with standard chemotherapy shrinks tumors in a greater proportion of patients and makes patients live longer than using standard chemotherapy alone. This has never been tested in urothelial cancer and we do not know if bevacizumab will have the same effects in this disease. The purpose of this study is to find out what effects, good and/or bad, the combination of gemcitabine, carboplatin, and bevacizumab has on you and your cancer.
Detailed description
This is a phase II trial of gemcitabine, carboplatin, and bevacizumab in chemotherapy naïve patients with advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract.
Interventions
DRUGBevacizumab
DRUGCarboplatin
DRUGGemcitabine
Sponsors
Memorial Sloan Kettering Cancer Center
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
* Histologic documentation: diagnosis of transitional cell carcinoma of the bladder,urethra, ureter, or renal pelvis. * Unresectable or metastatic disease * Ineligible for cisplatin (or incurable with cisplatin) * ≥ 4 weeks since prior RT * Karnofsky Performance Status ≥ 60% * Age ≥ 18 years of age * Required Initial Laboratory Values: Absolute neutrophil count ≥ 1.2 x 109/L; Platelets ≥ 100 x 109/L; Bilirubin ≤ 1.5 times the upper limit of normal (x ULN) for the institution; Aspartate transaminase (AST) and alanine transaminase(ALT) ≤ 3.0 x ULN;Serum creatinine \< 2.0 or calculated creatinine clearance (CrCl) ≥ 30 mL/min
Exclusion criteria
* Prior treatment with systemic chemotherapy (prior intravesical therapy is permitted) * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study * Blood pressure of \>150/100 mmHg * Unstable angina * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction within 6 months * History of stroke within 6 months * Clinically significant peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Presence of central nervous system or brain metastases * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0 * Anticipation of need for major surgical procedure during the course of the study * Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0 * Pregnant (positive pregnancy test) or lactating * Albuminuria as demonstrated by a urinary albumin of greater or = to 1.0 g/24 hr at screening * History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 6 months prior to Day 0 * Serious, non-healing wound, ulcer, or bone fracture * Inability to comply with study and/or follow-up procedures * History of persistent gross hematuria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Time to Disease Progression | 3 years | Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee \[JNCI, 92(3):205-216, 2000\]. Changes in only the largest diameter (uni-dimensional measurement) are used in the RECIST criteria. |
Secondary
| Measure | Time frame |
|---|---|
| The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC. | 3 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses. | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 36 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Region of Enrollment United States | 51 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 51 |
| serious Total, serious adverse events | 29 / 51 |
Outcome results
Primary
Evaluate the Time to Disease Progression
Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee \[JNCI, 92(3):205-216, 2000\]. Changes in only the largest diameter (uni-dimensional measurement) are used in the RECIST criteria.
Time frame: 3 years
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment | Evaluate the Time to Disease Progression | Time to Progression | 6.5 months |
| Treatment | Evaluate the Time to Disease Progression | Overall Survival | 13.9 months |
Secondary
The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC.
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC. | 49 percentage of participants |