Clinical trial NCT00645593: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: Bladder Cancer
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
name: Bristol-Myers Squibb
name: Eli Lilly and Company
First posted: 2008-03-27
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants That Respond to Treatment in Arm 1 and Arm 2
timeFrame: 3 years
Secondary outcomes:
measure: The Number of Grade 3 to 5 Adverse Events Experienced by Arm 1 and Arm 2
timeFrame: 3 years
measure: Median Progression-free Survival Time in Months
timeFrame: 3 years
measure: Median Overall Survival in Months
timeFrame: 3 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Los Angeles
country: United States
facility: Kenneth J. Norris Jr. Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Center of Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Michigan
name: Maha Hussain, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.