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Study of Gemcitabine and Cisplatin With or Without Cetuximab in Urothelial Cancer

Primary Purpose

Bladder Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine,
Cisplatin
Cetuximab
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring Bladder Cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Study participants will be male or female at least 18 years of age
  • Study participants will have a histologic/cytologic diagnosis of urothelial carcinoma (transitional cell carcinoma; either pure or mixed histology) that is metastatic, locally recurrent, or unresectable (T4bN0 or any T, N2030)
  • Study participants must have measurable disease by radiologic imaging. Study participants that have received previous radiation therapy, recovered from side effects and have not had more than 25% of the bone marrow
  • Study participants must have adequate bone marrow function

Exclusion Criteria:

  • Study participants may not have received previous systemic chemotherapy for the current stage of disease with the following exception: prior neoadjuvant or adjuvant chemotherapy is allowed provided it has been at least 6 months since treatment with non-cisplatin containing regimens and > 1 year since treatment with a cisplatin containing regimen
  • Study participants may not have received prior therapy targeting the EGFR pathway
  • Study participants may not have a history or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan
  • Study participants may not have known HIV due to the intense nature of the chemotherapy in this trial
  • Study subjects may not have a history of congestive heart failure (CHF), chronic renal failure, active TIAs, recent (in the last 6 months) stroke, symptomatic pulmonary embolism (PE), or myocardial infarction.
  • Study participants with history of DVT or incidental or asymptomatic PE will be eligible for the study as deemed appropriate by the treating physician provided they continue prophylactic or full dose anticoagulation as per standards of care for the specific event.
  • Study participants must not have a prior grade 3 or 4 severe infusion reaction to monoclonal antibodies
  • Study participants may not be pregnant or breastfeeding
  • Study participants may not receive concurrent treatment on another therapeutic clinical trial.

Sites / Locations

  • City of Hope Cancer Center
  • Kenneth J. Norris Jr. Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
  • Stanford University
  • Robert H. Lurie Comprehensive Cancer Center, Center of Northwestern University
  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Boston Medical Center
  • Lahey Clinic
  • University of Michigan
  • Wayne State University/Karmanos Cancer Institute
  • Roswell Park Cancer Institute
  • Vanderbilt-Ingram Cancer Center
  • University of Texas MD Anderson Cancer Center
  • University of Utah Huntsman Cancer Institute
  • University of Washington

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm 1, Gemcitabine and Cisplatin

Arm 2, Cetuximab, Gemcitabine and Cisplatin

Arm Description

Gemcitabine and Cisplatin, as described in the intervention

Gemcitabine and Cisplatin with Cetuximab, as described in the intervention

Outcomes

Primary Outcome Measures

Percentage of Participants That Respond to Treatment in Arm 1 and Arm 2
The primary objective is to compare the overall response rate of participants with locally advanced or metastatic urothelial carcinoma treated with gemcitabine and cisplatin with or without cetuximab. Overall response rate is defined as the percentage of participants that experience Complete Response (CR) (Disappearance of all target lesions) or Partial Response (PR) (>=30% decrease in the sum of the longest diameter of target lesions).

Secondary Outcome Measures

The Number of Grade 3 to 5 Adverse Events Experienced by Arm 1 and Arm 2
One of the secondary outcomes was to assess the safety and tolerability of treatment for both arms. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 were utilized for adverse event reporting.
Median Progression-free Survival Time in Months
Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions.
Median Overall Survival in Months
Median overall survival in months is provided. One participant who progressed from chemotherapy in arm 1 received cyclophosphamide and achieved long-term disease control therefore there is no upper limit for the 95% confidence interval.

Full Information

First Posted
March 24, 2008
Last Updated
April 14, 2016
Sponsor
University of Michigan Rogel Cancer Center
Collaborators
National Comprehensive Cancer Network, Bristol-Myers Squibb, Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00645593
Brief Title
Study of Gemcitabine and Cisplatin With or Without Cetuximab in Urothelial Cancer
Official Title
Phase II Randomized Trial of Gemcitabine and Cisplatin With or Without Cetuximab in Patients With Urothelial Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
Collaborators
National Comprehensive Cancer Network, Bristol-Myers Squibb, Eli Lilly and Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will compare the effects, good and/or bad, of chemotherapy (Gemcitabine and Cisplatin) with or without the addition of the chemotherapy drug Cetuximab to find out which treatment is better.
Detailed Description
Urothelial cancer typically begins in the lining of the bladder, the balloon-shaped organ in the pelvic area that stores urine. Urothelial cancer can also begin in the ureter (the tube connecting the kidney and bladder), part of the kidney itself, or the urethra (the tube you pass urine out of). Some Urothelial cancers remain confined to the lining, while in other cases they spread to other areas. Treatment for these cancers varies greatly depending on the stage of disease at the time of diagnosis. Study participants in this research study will have a diagnosis of urothelial cancer that is advanced or has come back after prior therapy. There are two standard chemotherapeutic regimens for the management of this disease. One is the combination of the drugs, methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). However the toxicities associated with this treatment regimen (side effects) is high. The other is a combination of two drugs called Cisplatin and Gemcitabine. These drugs are also known to destroy urothelial cancer cells, and are better tolerated by patients. All study participants will receive both of these drugs. Another anti-cancer drug called Cetuximab is known to delay or prevent tumor growth and in some cases to lead to death of cancer cells by blocking certain cellular pathways that lead to tumor development. This drug has been approved by the United States Food and Drug Administration (FDA) for the treatment of colorectal cancer and for treatment of head and neck cancers. The use of Cetuximab for the treatment of urothelial cancer is investigational in this study. The purpose of this study is to compare the safety and efficacy of Gemcitabine and Cisplatin administered with or without the addition of Cetuximab in study participants with urothelial cancer. This is a randomized research study. Study participants will be randomized to receive either gemcitabine and cisplatin alone or in combination with Cetuximab.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
Bladder Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
89 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1, Gemcitabine and Cisplatin
Arm Type
Active Comparator
Arm Description
Gemcitabine and Cisplatin, as described in the intervention
Arm Title
Arm 2, Cetuximab, Gemcitabine and Cisplatin
Arm Type
Experimental
Arm Description
Gemcitabine and Cisplatin with Cetuximab, as described in the intervention
Intervention Type
Drug
Intervention Name(s)
Gemcitabine,
Other Intervention Name(s)
Gemzar
Intervention Description
Gemcitabine will be administered intravenously at a dose of 1000 mg/m2 on Days 1, 8 and 15 of cycle. One treatment cycle is 28 days.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle.
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
Cetuximab will be administered intravenously at a dose of 500 mg/m2 on Days 1 and 15 of each cycle. One treatment cycle is 28 days.
Primary Outcome Measure Information:
Title
Percentage of Participants That Respond to Treatment in Arm 1 and Arm 2
Description
The primary objective is to compare the overall response rate of participants with locally advanced or metastatic urothelial carcinoma treated with gemcitabine and cisplatin with or without cetuximab. Overall response rate is defined as the percentage of participants that experience Complete Response (CR) (Disappearance of all target lesions) or Partial Response (PR) (>=30% decrease in the sum of the longest diameter of target lesions).
Time Frame
3 years
Secondary Outcome Measure Information:
Title
The Number of Grade 3 to 5 Adverse Events Experienced by Arm 1 and Arm 2
Description
One of the secondary outcomes was to assess the safety and tolerability of treatment for both arms. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 were utilized for adverse event reporting.
Time Frame
3 years
Title
Median Progression-free Survival Time in Months
Description
Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions.
Time Frame
3 years
Title
Median Overall Survival in Months
Description
Median overall survival in months is provided. One participant who progressed from chemotherapy in arm 1 received cyclophosphamide and achieved long-term disease control therefore there is no upper limit for the 95% confidence interval.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Study participants will be male or female at least 18 years of age Study participants will have a histologic/cytologic diagnosis of urothelial carcinoma (transitional cell carcinoma; either pure or mixed histology) that is metastatic, locally recurrent, or unresectable (T4bN0 or any T, N2030) Study participants must have measurable disease by radiologic imaging. Study participants that have received previous radiation therapy, recovered from side effects and have not had more than 25% of the bone marrow Study participants must have adequate bone marrow function Exclusion Criteria: Study participants may not have received previous systemic chemotherapy for the current stage of disease with the following exception: prior neoadjuvant or adjuvant chemotherapy is allowed provided it has been at least 6 months since treatment with non-cisplatin containing regimens and > 1 year since treatment with a cisplatin containing regimen Study participants may not have received prior therapy targeting the EGFR pathway Study participants may not have a history or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan Study participants may not have known HIV due to the intense nature of the chemotherapy in this trial Study subjects may not have a history of congestive heart failure (CHF), chronic renal failure, active TIAs, recent (in the last 6 months) stroke, symptomatic pulmonary embolism (PE), or myocardial infarction. Study participants with history of DVT or incidental or asymptomatic PE will be eligible for the study as deemed appropriate by the treating physician provided they continue prophylactic or full dose anticoagulation as per standards of care for the specific event. Study participants must not have a prior grade 3 or 4 severe infusion reaction to monoclonal antibodies Study participants may not be pregnant or breastfeeding Study participants may not receive concurrent treatment on another therapeutic clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maha Hussain, M.D.
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Kenneth J. Norris Jr. Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Robert H. Lurie Comprehensive Cancer Center, Center of Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Lahey Clinic
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-3721
Country
United States
Facility Name
University of Utah Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24802654
Citation
Hussain M, Daignault S, Agarwal N, Grivas PD, Siefker-Radtke AO, Puzanov I, MacVicar GR, Levine EG, Srinivas S, Twardowski P, Eisenberger MA, Quinn DI, Vaishampayan UN, Yu EY, Dawsey S, Day KC, Day ML, Al-Hawary M, Smith DC. A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma. Cancer. 2014 Sep 1;120(17):2684-93. doi: 10.1002/cncr.28767. Epub 2014 May 6.
Results Reference
derived

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Study of Gemcitabine and Cisplatin With or Without Cetuximab in Urothelial Cancer

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