Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/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: NCT00588666
Recruitment Status : Completed
First Posted : January 8, 2008
Results First Posted : January 22, 2016
Last Update Posted : January 22, 2016
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:

Gemcitabine and carboplatin are two standard chemotherapy drugs used to treat tumors of the urothelial tract. 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. One new class of drugs are called 'angiogenesis-inhibitors'. 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. Bevacizumab is an anti-angiogenic drug.

In some other cancers such as colon cancer and lung cancer, combining bevacizumab with standard chemotherapy shrinks tumors in a greater proportion of patients and makes patients live longer than using standard chemotherapy alone. This has never been tested in urothelial cancer and we do not know if bevacizumab will have the same effects in this disease. The purpose of this study is to find out what effects, good and/or bad, the combination of gemcitabine, carboplatin, and bevacizumab has on you and your cancer.

Condition or disease Intervention/treatment Phase
Myeloproliferative Disorder Urothelial Carcinoma Cancer Drug: Bevacizumab Drug: Carboplatin Drug: Gemcitabine Phase 2

Detailed Description:
This is a phase II trial of gemcitabine, carboplatin, and bevacizumab in chemotherapy naïve patients with advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma
Study Start Date : May 2006
Actual Primary Completion Date : December 2011
Actual Study Completion Date : December 2011

Arm Intervention/treatment
Experimental: Bevacizumab, Carboplatin, Gemcitabine
Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
Drug: Bevacizumab Drug: Carboplatin Drug: Gemcitabine

Primary Outcome Measures :
  1. Evaluate the Time to Disease Progression [ Time Frame: 3 years ]
    Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI, 92(3):205-216, 2000]. Changes in only the largest diameter (uni-dimensional measurement) are used in the RECIST criteria.

Secondary Outcome Measures :
  1. The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC. [ Time Frame: 3 years ]

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:

  • Histologic documentation: diagnosis of transitional cell carcinoma of the bladder,urethra, ureter, or renal pelvis.
  • Unresectable or metastatic disease
  • Ineligible for cisplatin (or incurable with cisplatin)
  • ≥ 4 weeks since prior RT
  • Karnofsky Performance Status ≥ 60%
  • Age ≥ 18 years of age
  • Required Initial Laboratory Values: Absolute neutrophil count ≥ 1.2 x 109/L; Platelets ≥ 100 x 109/L; Bilirubin ≤ 1.5 times the upper limit of normal (x ULN) for the institution; Aspartate transaminase (AST) and alanine transaminase(ALT) ≤ 3.0 x ULN;Serum creatinine < 2.0 or calculated creatinine clearance (CrCl) ≥ 30 mL/min

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 other than a Genentech-sponsored bevacizumab cancer study
  • Blood pressure of >150/100 mmHg
  • Unstable angina
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction within 6 months
  • History of stroke 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
  • Anticipation of need for major surgical procedure during the course of the study
  • Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
  • Pregnant (positive pregnancy test) or lactating
  • Albuminuria as demonstrated by a urinary albumin of greater or = to 1.0 g/24 hr at screening
  • 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

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): NCT00588666

United States, New Jersey
Memorial Sloan-Kettering at Basking Ridge
Basking Ridge, New Jersey, United States, 07920
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk
Commack, New York, United States, 11725
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center
Rockville Centre, New York, United States, 11570
Memoral Sloan Kettering Cancer Center@Phelps
Sleepy Hollow, New York, United States
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Principal Investigator: Dean Bajorin, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT00588666     History of Changes
Other Study ID Numbers: 06-006
First Posted: January 8, 2008    Key Record Dates
Results First Posted: January 22, 2016
Last Update Posted: January 22, 2016
Last Verified: December 2015

Keywords provided by Memorial Sloan Kettering Cancer Center:
Myeloproliferative Disorder
urinary bladder
renal pelvis

Additional relevant MeSH terms:
Carcinoma, Transitional Cell
Myeloproliferative Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors