Clinical trial NCT01589094: Neoadjuvant Dose Dense Gemcitabine and Cisplatin (DD GC) In Patients With Muscle-Invasive Bladder Cancer
Official title: Phase II Study of Neoadjuvant Dose Dense Gemcitabine and Cisplatin (DD GC) In Patients With Muscle-Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: CISPLATIN
GEMCITABINE
GM-CSF
radical cystectomy
12-071
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: University of North Carolina, Chapel Hill
name: New York University
First posted: 2012-05-01
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pathologic Response Rate
timeFrame: 1 year
Secondary outcomes:
measure: Number of Participants With Toxicity
timeFrame: 1 year
measure: 2 Year Recurrence Free Survival (RFS) Rate for Responders
timeFrame: 2 years
measure: 2 Year Recurrence Free Survival (RFS) Rate for Nonresponders
timeFrame: 2 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering at Basking Ridge
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center @ Suffolk
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering West Harrison
state: New York
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Cancer Center at Mercy Medical Center
state: New York
city: Sleepy Hollow
country: United States
facility: Memoral Sloan Kettering Cancer Center@Phelps
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Dean Bajorin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Iyer G, Balar AV, Milowsky MI, Bochner BH, Dalbagni G, Donat SM, Herr HW, Huang WC, Taneja SS, Woods M, Ostrovnaya I, Al-Ahmadie H, Arcila ME, Riches JC, Meier A, Bourque C, Shady M, Won H, Rose TL, Kim WY, Kania BE, Boyd ME, Cipolla CK, Regazzi AM, Delbeau D, McCoy AS, Vargas HA, Berger MF, Solit DB, Rosenberg JE, Bajorin DF. Multicenter Prospective Phase II Trial of Neoadjuvant Dose-Dense Gemcitabine Plus Cisplatin in Patients With Muscle-Invasive Bladder Cancer. J Clin Oncol. 2018 Jul 1;36(19):1949-1956. doi: 10.1200/JCO.2017.75.0158. Epub 2018 May 9.