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

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00714948
First received: July 10, 2008
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Bladder Cancer
URINARY BLADDER
Drug: gemcitabine and cisplatin plus sorafenib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine the progression free survival rate at one year for previously untreated patients with advanced/metastatic urothelial carcinoma treated with the combination of sorafenib, gemcitabine, and cisplatin. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]
  • To define the response rate of combination therapy with sorafenib, gemcitabine, and cisplatin in patients with advanced/metastatic urothelial carcinoma. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To define the safety of combination therapy with sorafenib, gemcitabine, and cisplatin in patients with advanced/metastatic urothelial carcinoma. [ Time Frame: conclusion of the study ] [ Designated as safety issue: Yes ]
  • To estimate the overall survival for patients with advanced/metastatic urothelial carcinoma receiving combination therapy with sorafenib, gemcitabine, and cisplatin. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]
  • To estimate the progression free survival distribution for patients with advanced/metastatic urothelial carcinoma receiving combination therapy with sorafenib, gemcitabine, and cisplatin. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: July 2008
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00714948

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Bayer
Investigators
Principal Investigator: Matthew Milowsky, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00714948     History of Changes
Other Study ID Numbers: 07-168
Study First Received: July 10, 2008
Last Updated: January 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Bladder
Urinary
SORAFENIB
CISPLATIN
GEMCITABINE

Additional relevant MeSH terms:
Carcinoma, Transitional Cell
Urinary Bladder Neoplasms
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Cisplatin
Gemcitabine
Sorafenib
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014