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

• ClinicalTrials.gov Identifier: NCT00461851
• Recruitment Status: Completed
• First Posted: April 18, 2007
• Results First Posted: November 1, 2016
• Last Update Posted: December 14, 2017
• Sponsor: Yale University
• Collaborator: Bayer
• Information provided by (Responsible Party): Yale University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Bladder Cancer	Drug: Gemcitabine; Drug: Carboplatin; Drug: Sorafenib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: March 2007
• Actual Primary Completion Date: August 2013
• Actual Study Completion Date: August 2013

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: Upon completion of study ]
   The primary outcome was the proportion of patients who achieved progression free survival (PFS) of five months. PFS was defined as time to progression or any-cause mortality, whichever came first.

Secondary Outcome Measures :

1. Dose Ruction (Toxicity) [ Time Frame: Upon completion of study ]
   To determine the toxicity of combination therapy with sorafenib, gemcitabine and carboplatin, dose reductions by drug are reported. The number of patients that were reduced in dosage are reported here.
2. Best Reported Response [ Time Frame: Upon completion of study ]
   The best reported response captures 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00461851
• Other Study ID Numbers: 0609001823
• First Posted: April 18, 2007
• Results First Posted: November 1, 2016
• Last Update Posted: December 14, 2017
• Last Verified: September 2016

Keywords provided by Yale University:

Advanced/Metastatic Bladder Carcinoma

Additional relevant MeSH terms:

Carcinoma; Urinary Bladder Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urinary Bladder Diseases; Urologic Diseases; Gemcitabine; Carboplatin; Sorafenib; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Protein Kinase Inhibitors