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

Primary Purpose

Myeloproliferative Disorder, Urothelial Carcinoma, Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
Carboplatin
Gemcitabine
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myeloproliferative Disorder focused on measuring Myeloproliferative Disorder, urinary bladder, Cancer, ureter, renal pelvis, chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan-Kettering at Basking Ridge
  • Memoral Sloan Kettering Cancer Center
  • Memorial Sloan-Kettering Cancer Center @ Suffolk
  • Memorial Sloan-Kettering Cancer Center
  • Memorial Sloan-Kettering Cancer Center at Mercy Medical Center
  • Memoral Sloan Kettering Cancer Center@Phelps

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bevacizumab, Carboplatin, Gemcitabine

Arm Description

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.

Outcomes

Primary Outcome Measures

Evaluate the Time to Disease Progression
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

The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC.

Full Information

First Posted
December 26, 2007
Last Updated
December 16, 2015
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00588666
Brief Title
Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma
Official Title
Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
May 2006 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloproliferative Disorder, Urothelial Carcinoma, Cancer
Keywords
Myeloproliferative Disorder, urinary bladder, Cancer, ureter, renal pelvis, chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab, Carboplatin, Gemcitabine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Primary Outcome Measure Information:
Title
Evaluate the Time to Disease Progression
Description
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.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dean Bajorin, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering at Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memoral Sloan Kettering Cancer Center
City
Basking Ridge
State/Province
New Jersey
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center @ Suffolk
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center
City
Rockville Centre
State/Province
New York
ZIP/Postal Code
11570
Country
United States
Facility Name
Memoral Sloan Kettering Cancer Center@Phelps
City
Sleepy Hollow
State/Province
New York
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org
Description
Memorial Sloan-Kettering web site

Learn more about this trial

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

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