Clinical trial NCT00847015: Gemcitabine, Cisplatin, and Sunitinib (GC-S) as Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer
Official title: Phase II Study of Gemcitabine, Cisplatin, and Sunitinib (GC-S) as Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Urinary Bladder
Keywords: Bladder
Urinary
CISPLATIN
GEMCITABINE
SU011248 (Sunitinib Malate)
08-159
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2009-02-19
Enrollment: 18
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The Pathologic Complete Response Rate (<pT0) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer.
timeFrame: 2 years
Secondary outcomes:
measure: The Pathologic Response Rate (<pT2) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer.
timeFrame: 2 years
measure: The Time to Disease Progression in Patients With Muscle Invasive Urothelial Carcinoma of the Bladder Treated With Neoadjuvant GCS Followed by Radical Cystectomy.
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: 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
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Dean Bajorin, MD
role: PRINCIPAL_INVESTIGATOR
References: