Neoadjuvant Dose Dense Gemcitabine and Cisplatin (DD GC) In Patients With Muscle-Invasive Bladder Cancer

Phase 2

Completed

Brief Summary: The purpose of this study is to find out if standard chemotherapy (gemcitabine and cisplatin) given on a dose-dense treatment schedule (with less time between treatments) can help shrink the tumor better than standard chemotherapy given on a standard treatment schedule before the patient undergoes surgery for bladder cancer.

Recruitment & Eligibility

Inclusion Criteria

Muscle invasive urothelial carcinoma of the bladder histologically confirmed at MSKCC or participating site ((Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or EUA.)
Clinical stage T2-T4a N0/X M0 disease
Medically appropriate candidate for radical cystectomy, as per MSKCC or participating site
Karnofsky Performance Status ≥ 70%
Age ≥ 18 years of age
Required Initial Laboratory Values:
Absolute Neutrophil Count ≥ 1000 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

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 ≥ 2 neuropathy
Preexisting grade ≥ 2 hearing loss
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
Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2
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
Pregnancy or breast-feeding. Patients must be surgically sterile, 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.

Arm && Interventions

Group	Intervention	Description
Gemcitabine and Cisplatin (DD GC)	Gemcitabine and Cisplatin (DD GC)	This is a Multicenter Phase II study of dose-dense (DD) gemcitabine and cisplatin (GC) neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC) who are candidates for radical cystectomy.

Primary Outcome Measures

Name	Time	Method
Pathologic Response Rate	1 year	Defined as the absence of muscle invasive carcinoma (\<pT2 disease) and the absence of lymph node metastases (N0) on the final cystectomy specimen. Pathologists will assess surgical specimens systematically using criteria agreed upon for all conventional neoadjuvant treatment based on the AJCC TNM staging system.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Toxicity	1 year	Toxicity will be graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0.
2 Year Recurrence Free Survival (RFS) Rate for Responders	2 years	Defined as the time from treatment initiation to disease progression, local-regional or metastatic recurrence, or death analyzed using the Kaplan Meier method.
2 Year Recurrence Free Survival (RFS) Rate for Nonresponders	2 years	Defined as the time from treatment initiation to disease progression, local-regional or metastatic recurrence, or death analyzed using the Kaplan Meier method.

Locations (8): University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States
Memoral Sloan Kettering Cancer Center@Phelps
🇺🇸
Sleepy Hollow, New York, United States
Memorial Sloan Kettering Cancer Center @ Suffolk
🇺🇸
Commack, New York, United States
Memorial Sloan Kettering at Basking Ridge
🇺🇸
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Cancer Center at Mercy Medical Center
🇺🇸
Rockville Centre, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
New York University
🇺🇸
New York, New York, United States
Memorial Sloan Kettering West Harrison
🇺🇸
Harrison, New York, United States