Bladder Cancer, Urinary Bladder
Conditions
Keywords
Bladder, Urinary, CISPLATIN, GEMCITABINE, SU011248 (Sunitinib Malate), 08-159
Brief summary
The purpose of this study is to find out if using the combination of standard chemotherapy (gemcitabine and cisplatin) plus this new targeted pill (sunitinib) can help shrink your tumor before you undergo surgery for your bladder cancer.
Interventions
DRUGSunitinib
Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period.
DRUGGemcitabine
Gemcitabine 1,000 mg/m\^2
DRUGcisplatin
cisplatin 35 mg/m\^2 will be administered intravenously on days 1 and 8.
Sponsors
Pfizer
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
* Histologically confirmed muscle invasive transitional cell carcinoma of the bladder at MSKCC. * Clinical stage T2-T4a N0/X M0 disease. * Medically appropriate candidate for radical cystectomy as per MSKCC attending urologic oncologist. * Karnofsky Performance Status ≥ 70%. * Age ≥ 18 years of age. * Required Initial Laboratory Values: * Absolute neutrophil count ≥ 1500 cells/mm3 * Platelets ≥ 100,000 cells/mm3 * Hemoglobin ≥ 9.0g/dL * Bilirubin ≤ 1.5 the upper limit of normal (ULN) for the institution * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution * Alkaline phosphatase ≤ 2.5 x ULN for the institution * Serum creatinine ≤ 1.5 mg/dL * Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 using the CKD-EPI equation: * eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 1)-1.209 x 0.993Age * x 1.018 \[if female\] x 1.159 \[if black\] * Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1. * If female of childbearing potential, pregnancy test is negative. * Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial.
Exclusion criteria
* Prior systemic chemotherapy (prior intravesical therapy is allowed) * Prior radiation therapy to the bladder * Evidence of NYHA functional class III or IV heart disease. * Serious intercurrent medical or psychiatric illness, including serious active infection. * Preexisting sensory grade 3 neuropathy * Major surgery or radiation therapy \< 4 weeks of starting study treatment. * Concomitant use of any other investigational drugs * Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism. * Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade ≥ 2. * Prolonged QTc interval on baseline EKG (\>450 msec for males and \>470 msec for females). * Uncontrolled hypertension (\>150/100 mmHg despite optimal medical therapy). * Pre-existing thyroid abnormality, with thyroid function tests that cannot be maintained in the normal range with medication. * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. * Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, are allowed. * Ongoing treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg po daily for thromboembolic prophylaxis is allowed). * Pregnancy or breast-feeding. Patients must be surgically sterile or be postmenopausal,or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Pathologic Complete Response Rate (<pT0) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer. | 2 years | Complete pathologic response to neoadjuvant GCS is the primary endpoint is defined as the absence of carcinoma (pT0 disease) and the absence of microscopic lymph node metastases (N0) on the final cystectomy specimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Pathologic Response Rate (<pT2) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer. | 2 years | is defined as the absence of muscle invasive carcinoma (\<pT2 disease) and the absence of microscopic lymph node metastases (N0) on the final cystectomy specimen. |
| The Time to Disease Progression in Patients With Muscle Invasive Urothelial Carcinoma of the Bladder Treated With Neoadjuvant GCS Followed by Radical Cystectomy. | 2 years | The time to disease progression is measured from the time of initiation of chemotherapy until the first date that systemic recurrence is objectively documented. Systemic recurrence for this trial is defined as either metastatic or local pelvic recurrence. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine, Cisplatin, and Sunitinib This is a phase II study of GCS (Gemcitabine, Cisplatin, and Sunitinib) as neoadjuvant chemotherapy in patients with muscle-invasive urothelial carcinoma of the bladder. Patients with muscle invasive urothelial carcinoma who are candidates for radical cystectomy will be enrolled.
Gemcitabine, Cisplatin, and Sunitinib: Patients will receive four cycles of GCS administered every 21 days followed by radical cystectomy. Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period. Gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 8. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | declined any surgery | 1 |
| Overall Study | partial cystectomy vs radical cystectomy | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Gemcitabine, Cisplatin, and Sunitinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 14 / 18 |
Outcome results
Primary
The Pathologic Complete Response Rate (<pT0) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer.
Complete pathologic response to neoadjuvant GCS is the primary endpoint is defined as the absence of carcinoma (pT0 disease) and the absence of microscopic lymph node metastases (N0) on the final cystectomy specimen.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine, Cisplatin, and Sunitinib | The Pathologic Complete Response Rate (<pT0) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer. | 6.67 percentage of participants |
Secondary
The Pathologic Response Rate (<pT2) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer.
is defined as the absence of muscle invasive carcinoma (\<pT2 disease) and the absence of microscopic lymph node metastases (N0) on the final cystectomy specimen.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine, Cisplatin, and Sunitinib | The Pathologic Response Rate (<pT2) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer. | 33 percentage of participants |
Secondary
The Time to Disease Progression in Patients With Muscle Invasive Urothelial Carcinoma of the Bladder Treated With Neoadjuvant GCS Followed by Radical Cystectomy.
The time to disease progression is measured from the time of initiation of chemotherapy until the first date that systemic recurrence is objectively documented. Systemic recurrence for this trial is defined as either metastatic or local pelvic recurrence.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine, Cisplatin, and Sunitinib | The Time to Disease Progression in Patients With Muscle Invasive Urothelial Carcinoma of the Bladder Treated With Neoadjuvant GCS Followed by Radical Cystectomy. | 10 months |