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

NCT ID: NCT00461851

Last Updated: 2017-12-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2013-08-31

Brief Summary

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.

Conditions

Bladder Cancer

Keywords

Advanced/Metastatic Bladder Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Gemcitabine will be given at a standard dose schedule of 1000 mg/m² on day 1 and 8.

Carboplatin

Intervention Type: DRUG

Carboplatin will be given on day 1 to an AUC of 5.

Sorafenib

Intervention Type: DRUG

Sorafenib will be administered orally daily on days 2-19 at 400 mg bid

Interventions

Gemcitabine

Gemcitabine will be given at a standard dose schedule of 1000 mg/m² on day 1 and 8.

Intervention Type: DRUG

Carboplatin

Carboplatin will be given on day 1 to an AUC of 5.

Intervention Type: DRUG

Sorafenib

Sorafenib will be administered orally daily on days 2-19 at 400 mg bid

Intervention Type: DRUG

Other Intervention Names

Gemzar; BAY 43-9006

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hari Deshpande, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University, Comprehensive Cancer Center

New Haven, Connecticut, United States

Countries

United States

Other Identifiers

0609001823

Identifier Type: -

Identifier Source: org_study_id