Gemcitabine and Split-dose Cisplatin (GC) Plus Sorafenib in Chemotherapy-naïve Patients With Locally Advanced or Metastatic Urothelial Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00714948
Recruitment Status : Terminated (Lack of accrual)
First Posted : July 14, 2008
Results First Posted : November 16, 2015
Last Update Posted : November 16, 2015
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:

Standard chemotherapy drugs generally work by killing rapidly dividing cells in your body. Cancers cells are some of the most rapidly dividing cells and that is why chemotherapy can be effective in some patients. Gemcitabine and Cisplatin are an effective and standard drug combination used to treat locally advanced and metastatic urothelial cancer. However, these drugs do not shrink tumors in all patients and when they do, it is generally for a limited amount of time. This has led scientists to look for different ways to treat cancer.

New drugs have been developed to treat cancer that work differently than standard chemotherapy drugs. These drugs attempt to decrease the blood supply to tumors. By doing so, this may limit the tumor's source of oxygen and nutrients and prevent the tumor from growing. Sorafenib is an example of a drug that works in this way.

In some patients with advanced kidney cancer, sorafenib alone has been shown to slow the progression of their disease. The purpose of this study is to find out what effects, good and/or bad, the combination of gemcitabine, cisplatin, and sorafenib has on you and your cancer.

Condition or disease Intervention/treatment Phase
Bladder Cancer URINARY BLADDER Drug: gemcitabine and cisplatin plus sorafenib Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Gemcitabine and Split-dose Cisplatin (GC) Plus Sorafenib in Chemotherapy-naïve Patients With Locally Advanced or Metastatic Urothelial Carcinoma
Study Start Date : July 2008
Actual Primary Completion Date : November 2011
Actual Study Completion Date : November 2011

Arm Intervention/treatment
Experimental: 1
This is a phase II trial of gemcitabine and Split-dose cisplatin plus sorafenib.
Drug: gemcitabine and cisplatin plus sorafenib
Gemcitabine 1000 mg/m 2 will be administered on days 1 and 8 and cisplatin 35 mg/m 2 will be administered on days 1 and 8. A total of six cycles of therapy will be administered at 21day intervals. Sorafenib 400 mg PO twice daily will be initiated on day 1 of cycle 1 and continued, as tolerated, until the time of disease progression or a maximum of 12 months. The total chemotherapy dose for gemcitabine and cisplatin (GC) may be modified for patients with severe obesity (e.g. body surface area (BSA) > 2.1), after consultation with the Principal Investigator.

Primary Outcome Measures :
  1. To Determine the Progression Free Survival Rate at One Year Untreated Patients With Advanced/Metastatic Urothelial Carcinoma Treated With the Combination of Sorafenib, Gemcitabine, and Cisplatin. [ Time Frame: conclusion of the study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have measurable or evaluable urothelial cancer.

    • Measurable disease includes unresectable or metastatic urothelial tract tumors that are unidimensionally measurable by xray,CT/MRI scan or physical examination.
    • Evaluable disease is restricted to patients with unresectable primary bladder tumors which can be evaluated for response by cystoscopy.
  • Pathologic confirmation by the Department of Pathology at MSKCC.
  • Karnofsky Performance Status (KPS) ≥60%.
  • Adequate marrow function defined as granulocytes ≥ 1500 cells/mm 3 , platelets ≥ 100,000 cells/mm 3 , and hemoglobin ≥ 8.0 g/dl.
  • Serum creatinine < 2.0 mg/dl
  • 24-hour urine sample demonstrating creatinine clearance ≥ 60 ml/min/1.73m2 or calculated creatinine clearance ≥ 60 ml/min/1.73m 2 using the formula: Jeliffe Equation: estimated creatinine clearance = 98 x (0.8 [age(yrs) 20]/Serum Creatinine (mg/dL) x (0.9 if Female))
  • Adequate hepatic function defined as:

    • Total Bilirubin < or = to 1.5 x ULN
    • AST and ALT < or = to 3.0 x ULN (< or = to 5.0 x ULN is acceptable if liver has tumor involvement)
  • Normal coagulation profile including PT/INR and PTT, unless patient is receiving anticoagulation therapy with agents such as warfarin or heparin.
  • Age ≥ 18 years
  • Informed consent
  • Women of childbearing potential must have a negative pregnancy test.
  • Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
  • Patients are encouraged to continue barrier method contraception for two years or longer after treatment.

Exclusion Criteria:

  • Prior treatment with systemic chemotherapy (prior intravesical therapy is permitted).
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
  • Blood Pressure of > 150/100 mm Hg.
  • Irradiation within 4 weeks of start of protocol.
  • Evidence of another active cancer, except for nonmelanoma skin carcinoma, insitu carcinoma of the cervix curatively treated, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is nondetectable.
  • Significant cardiovascular disease including congestive heart failure (New York Heart Association Class II or higher) or active angina pectoris.
  • History of a myocardial infarction within 6 months.
  • History of a stroke or transient ischemic attack within 6 months.
  • Clinically significant peripheral vascular disease.
  • Evidence of bleeding diathesis or coagulopathy.
  • Presence of central nervous system or brain metastases.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0.
  • Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0.
  • History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 0.
  • Serious nonhealing wound, ulcer, or bone fracture.
  • History of persistent gross hematuria.
  • Uncontrolled infection.
  • Hypersensitivity to sorafenib, or any component of the formulation.
  • Pregnant (positive pregnancy test) or lactating.
  • Inability to comply with the study and/or followup procedures.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00714948

United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Principal Investigator: Matthew Milowsky, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT00714948     History of Changes
Other Study ID Numbers: 07-168
First Posted: July 14, 2008    Key Record Dates
Results First Posted: November 16, 2015
Last Update Posted: November 16, 2015
Last Verified: October 2015

Keywords provided by Memorial Sloan Kettering Cancer Center:

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Vitamin B Complex
Growth Substances