Gemcitabine, Cisplatin, and Sunitinib (GC-S) as Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer

Phase 2

Completed

Conditions: Bladder Cancer
Urinary Bladder

Interventions: Drug: Sunitinib
Drug: Gemcitabine
Drug: cisplatin

Registration Number: NCT00847015

Lead Sponsor: Memorial Sloan Kettering Cancer Center

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 18

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gemcitabine, Cisplatin, and Sunitinib	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	cisplatin	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	Gemcitabine	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (5): Memorial Sloan-Kettering at Basking Ridge
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Basking Ridge, New Jersey, United States
Memorial Sloan-Kettering Cancer Center @ Suffolk
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Commack, New York, United States
Memoral Sloan Kettering Cancer Center@Phelps
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Sleepy Hollow, New York, United States
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center
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Rockville Centre, New York, United States
Memorial Sloan-Kettering Cancer Center
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New York, New York, United States