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

• ClinicalTrials.gov Identifier: NCT00645593
• Recruitment Status: Completed
• First Posted: March 27, 2008
• Results First Posted: October 27, 2014
• Last Update Posted: May 23, 2016
• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: National Comprehensive Cancer Network; Bristol-Myers Squibb; Eli Lilly and Company
• Information provided by (Responsible Party): University of Michigan Rogel Cancer Center

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.

Condition or disease	Intervention/treatment	Phase
Bladder Cancer	Drug: Gemcitabine,; Drug: Cisplatin; Drug: Cetuximab	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Randomized Trial of Gemcitabine and Cisplatin With or Without Cetuximab in Patients With Urothelial Carcinoma
• Study Start Date: March 2008
• Actual Primary Completion Date: April 2014
• Actual Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm 1, Gemcitabine and Cisplatin; Gemcitabine and Cisplatin, as described in the intervention	Drug: Gemcitabine,; 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.; Other Name: Gemzar; Drug: Cisplatin; Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle.
Experimental: Arm 2, Cetuximab, Gemcitabine and Cisplatin; Gemcitabine and Cisplatin with Cetuximab, as described in the intervention	Drug: Gemcitabine,; 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.; Other Name: Gemzar; Drug: Cisplatin; Cisplatin will be administered intravenously at a dose of 70 mg/m2 per institutional standards on Day 1 of each cycle.; Drug: Cetuximab; 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.; Other Name: Erbitux

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants That Respond to Treatment in Arm 1 and Arm 2 [ Time Frame: 3 years ]

   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 :

1. The Number of Grade 3 to 5 Adverse Events Experienced by Arm 1 and Arm 2 [ Time Frame: 3 years ]

   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.

2. Median Progression-free Survival Time in Months [ Time Frame: 3 years ]
   Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions.
3. Median Overall Survival in Months [ Time Frame: 3 years ]
   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.

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:

• 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.

Contacts and Locations

Locations

United States, California

City of Hope Cancer Center

Duarte, California, United States, 91010

Kenneth J. Norris Jr. Comprehensive Cancer Center, Keck School of Medicine, University of Southern California

Los Angeles, California, United States, 90033

Stanford University

Stanford, California, United States, 94305

United States, Illinois

Robert H. Lurie Comprehensive Cancer Center, Center of Northwestern University

Chicago, Illinois, United States, 60611

United States, Maryland

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21231

United States, Massachusetts

Boston Medical Center

Boston, Massachusetts, United States, 02118

Lahey Clinic

Burlington, Massachusetts, United States, 01805

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263-0001

United States, Tennessee

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States, 37232

United States, Texas

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030-3721

United States, Utah

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

United States, Washington

University of Washington

Seattle, Washington, United States, 98109

Sponsors and Collaborators

University of Michigan Rogel Cancer Center

National Comprehensive Cancer Network

Bristol-Myers Squibb

Eli Lilly and Company

Investigators

• Principal Investigator: Maha Hussain, M.D.; University of Michigan

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT00645593
• Other Study ID Numbers: UMCC 2007.097
• First Posted: March 27, 2008
• Results First Posted: October 27, 2014
• Last Update Posted: May 23, 2016
• Last Verified: April 2016

Keywords provided by University of Michigan Rogel Cancer Center:

Bladder Cancer

Additional relevant MeSH terms:

Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Gemcitabine; Cetuximab; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological