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

• ClinicalTrials.gov Identifier: NCT00847015
• Recruitment Status: Completed
• First Posted: February 19, 2009
• Results First Posted: February 29, 2016
• Last Update Posted: February 29, 2016
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: Pfizer
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: February 18, 2009
• First Posted Date: February 19, 2009
• Results First Submitted Date: October 19, 2015
• Results First Posted Date: February 29, 2016
• Last Update Posted Date: February 29, 2016
• Study Start Date: February 2009
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 1, 2016)

The Pathologic Complete Response Rate (<pT0) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer. [ Time Frame: 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.

Original Primary Outcome Measures (submitted: February 18, 2009)

• To define the pathologic complete response rate (<pT0) of neoadjuvant GCS regimen in patients with muscle-invasive bladder cancer. [ Time Frame: conclusion of the study ]
• To determine the safety of the GCS regimen in patients with urothelial cancer. [ Time Frame: conclusion of the study ]

Current Secondary Outcome Measures (submitted: February 1, 2016)

• The Pathologic Response Rate (<pT2) of Neoadjuvant GCS Regimen in Patients With Muscle-invasive Bladder Cancer. [ Time Frame: 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.
• The Time to Disease Progression in Patients With Muscle Invasive Urothelial Carcinoma of the Bladder Treated With Neoadjuvant GCS Followed by Radical Cystectomy. [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: February 18, 2009)

• To define the pathologic response rate (<pT2) of neoadjuvant GCS regimen in patients with muscle-invasive bladder cancer. [ Time Frame: conclusion of the study ]
• To determine the time to disease progression in patients with muscle invasive urothelial carcinoma of the bladder treated with neoadjuvant GCS followed by radical cystectomy. [ Time Frame: conclusion of the study ]
• To determine overall survival of patients with muscle-invasive urothelial carcinoma of the bladder treated with neoadjuvant GCS followed by radical cystectomy. [ Time Frame: conclusion of the study ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Bladder Cancer
• Urinary Bladder

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.
• Drug: Gemcitabine
  Gemcitabine 1,000 mg/m^2
• Drug: cisplatin
  cisplatin 35 mg/m^2 will be administered intravenously on days 1 and 8.

Study Arms

Experimental: Gemcitabine, Cisplatin, and 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.

Interventions:

• Drug: Sunitinib
• Drug: Gemcitabine
• Drug: cisplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 8, 2012): 18
• Original Estimated Enrollment (submitted: February 18, 2009): 45
• Actual Study Completion Date: November 2012
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00847015
• Other Study ID Numbers: 08-159
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Memorial Sloan Kettering Cancer Center
• Study Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Pfizer

Investigators

• Principal Investigator: Dean Bajorin, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: February 2016