Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma - Full Text View

Sponsored by:	Memorial Sloan-Kettering Cancer Center
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00588666

Purpose

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	Intervention	Phase
Myeloproliferative Disorder Urothelial Carcinoma Cancer	Drug: Bevacizumab, Carboplatin, Gemcitabine	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Carboplatin Gemcitabine Gemcitabine hydrochloride Bevacizumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma

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

Primary Outcome Measures:

Evaluate the time to disease progression; To define the safety of combination therapy with bevacizumab, gemcitabine, and carboplatin in patients with advanced/metastatic TCC. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To define the response rate of combination therapy with bevacizumab, gemcitabine, and carboplatin in patients with advanced/metastatic TCC. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	47
Study Start Date:	May 2006
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment: Experimental	Drug: 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.

Arms

Assigned Interventions

Treatment: Experimental

Drug: 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.

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.

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00588666

Contacts

Contact: Dean Bajorin, MD

bajorind@mskcc.org

Locations

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

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:

Dean Bajorin, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering web site This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Dean Bajorin, MD )
Study ID Numbers:	06-006
Study First Received:	December 26, 2007
Last Updated:	January 6, 2009
ClinicalTrials.gov Identifier:	NCT00588666 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Myeloproliferative Disorder
urinary bladder
Cancer

ureter
renal pelvis
chemotherapy

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Hematologic Diseases
Myeloproliferative Disorders
Bevacizumab
Carboplatin
Carcinoma, Transitional Cell
Angiogenesis Inhibitors

Antiviral Agents
Immunosuppressive Agents
Carcinoma
Radiation-Sensitizing Agents
Bone Marrow Diseases
Gemcitabine
Neoplasms, Glandular and Epithelial
Transitional Cell Carcinoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Carcinoma, Transitional Cell
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Gemcitabine
Neoplasms by Histologic Type

Hematologic Diseases
Growth Substances
Myeloproliferative Disorders
Enzyme Inhibitors
Carboplatin
Antiviral Agents
Immunosuppressive Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Radiation-Sensitizing Agents
Bone Marrow Diseases
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009