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

Bladder Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00847015
• Other study ID #: 08-159
• Status: Completed
• Phase: Phase 2
• First received: February 18, 2009
• Last updated: February 1, 2016
• Start date: February 2009
• Est. completion date: November 2012

Study information

• Verified date: February 2016
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder
• Urinary Bladder Neoplasms

Intervention

Drug:
• Sunitinib
Sunitinib will be administered at a dose of 25mg orally once daily for 2 consecutive weeks followed by a 1 week rest period.
• Gemcitabine
Gemcitabine 1,000 mg/m^2
• cisplatin
cisplatin 35 mg/m^2 will be administered intravenously on days 1 and 8.

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering at Basking Ridge	Basking Ridge	New Jersey
United States	Memorial Sloan-Kettering Cancer Center @ Suffolk	Commack	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center at Mercy Medical Center	Rockville Centre	New York
United States	Memoral Sloan Kettering Cancer Center@Phelps	Sleepy Hollow	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	2 years	No
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 (	2 years	No
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.	2 years	No

External Links

•   Memorial Sloan-Kettering Cancer Center