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Trial of Gemcitabine, Carboplatin, and Sorafenib in Chemotherapy-naive Patients With Advanced/Metastatic Bladder Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Hari Deshpande, Yale University
ClinicalTrials.gov Identifier:
NCT00461851
First received: April 16, 2007
Last updated: June 22, 2014
Last verified: June 2014
  Purpose

This is a Phase II, nonrandomized multicenter study designed to evaluate time to progression and response proportion of patients with advanced or metastatic transitional cell carcinoma of bladder receiving 6 cycles of gemcitabine, carboplatin and sorafenib and then maintenance sorafenib.


Condition Intervention Phase
Bladder Cancer
Drug: Gemcitabine
Drug: Carboplatin
Drug: Sorafenib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter Trial of Gemcitabine, Carboplatin, and Sorafenib in Chemotherapy-naive Patients With Advanced/Metastatic Bladder Carcinoma

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • To evaluate the time to disease progression in patients with advanced/metastatic TCC treated with the combination of sorafenib, gemcitabine, and carboplatin. [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the overall safety and tolerability of combination therapy with sorafenib, gemcitabine and carboplatin [ Time Frame: Upon completion of study ] [ Designated as safety issue: Yes ]
  • To define the proportion of patients with advanced or metastatic transitional cell carcinoma of the bladder that achieve a complete or partial response to the combination therapy with sorafenib, gemcitabine, and carboplatin. [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: March 2007
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy plus sorafenib
Gemcitabine 1000 mg/m2 weekly x 2 weeks plus carboplatin AUC (Area under curve) 5 every 3 weeks plus sorafenib x 6 cycles then maintenance sorafenib alone
Drug: Gemcitabine
Gemcitabine will be given at a standard dose schedule of 1000 mg/m² on day 1 and 8.
Other Name: Gemzar
Drug: Carboplatin
Carboplatin will be given on day 1 to an AUC of 5.
Drug: Sorafenib
Sorafenib will be administered orally daily on days 2-19 at 400 mg bid
Other Name: BAY 43-9006

  Eligibility

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

Inclusion Criteria:

  • Histologic documentation of diagnosis of transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis
  • Unresectable, locally advanced or metastatic disease
  • CrCl ≥ 60 ml/min or serum creatinine < 1.5
  • ≥ 4 weeks since prior RT
  • ECOG Performance Status of 0 or 1 (Appendix I)
  • Age ≥ 18 years of age
  • Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men and women should use adequate birth control for at least 2 weeks after the last administration of sorafenib.
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
  • Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
  • Adequate bone marrow, liver and renal function as assessed by the following:

    • Hemoglobin > 9.0 g/dl
    • Absolute neutrophil count (ANC) ≥ 1,500/mm3
    • Platelet count ≥ 100,000/mm3
    • Total bilirubin ≤ 1.5 times ULN
  • ALT and AST ≤ 2.5 times the ULN ( ≤ 5 x ULN for patients with liver involvement)
  • INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.

Exclusion Criteria:

  • Prior treatment with systemic chemotherapy (prior intravesical chemotherapy is permitted, and adjuvant therapy is permitted if > 12 months have lapsed)
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study
  • Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • History of stroke within six months
  • Clinically significant peripheral vascular disease
  • Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  • Sorafenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any of the excipients.
  • Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
  • Active clinically serious infection > CTCAE Grade 2.
  • Thrombolytic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
  • Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug
  • Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug
  • Evidence or history of bleeding diathesis or coagulopathy
  • Major surgery, significant traumatic injury within 4 weeks of first study drug
  • Use of St. John's Wort or rifampin (rifampicin)
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial
  • Any condition that impairs patient's ability to swallow whole pills
  • Any malabsorption problem
  • Anticipation of need for major surgical procedure during the course of the study
  • Pregnant (positive pregnancy test) or lactating
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
  • Serious, non-healing wound, ulcer, or bone fracture
  • Inability to comply with study and/or follow-up procedures
  • History of persistent gross hematuria
  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: NCT00461851

Locations
United States, Connecticut
Yale University, Comprehensive Cancer Center
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Bayer
Investigators
Principal Investigator: Hari Deshpande, MD Yale University
  More Information

No publications provided

Responsible Party: Hari Deshpande, Assistant Professor of Medicine, Yale University
ClinicalTrials.gov Identifier: NCT00461851     History of Changes
Other Study ID Numbers: 0609001823
Study First Received: April 16, 2007
Last Updated: June 22, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Advanced/Metastatic Bladder Carcinoma

Additional relevant MeSH terms:
Carcinoma
Urinary Bladder Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Carboplatin
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 November 27, 2014