Clinical trial NCT00053209: Pemetrexed Disodium and Gemcitabine in Treating Patients With Advanced Cancer of the Urothelium
Official title: Phase II Trial Of Pemetrexed Disodium And Gemcitabine In Advanced Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Urethral Cancer
Keywords: metastatic transitional cell cancer of the renal pelvis and ureter
recurrent transitional cell cancer of the renal pelvis and ureter
regional transitional cell cancer of the renal pelvis and ureter
transitional cell carcinoma of the bladder
recurrent bladder cancer
stage III bladder cancer
stage IV bladder cancer
anterior urethral cancer
posterior urethral cancer
recurrent urethral cancer
urethral cancer associated with invasive bladder cancer
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-28
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining pemetrexed disodium with gemcitabine may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining pemetrexed disodium with gemcitabine in treating patients who have advanced cancer of the urothelium.

Detailed description: OBJECTIVES:

Primary

* Determine the response rate in patients with previously untreated advanced cancer of the urothelium treated with pemetrexed disodium and gemcitabine.
* Determine the toxicity of this regimen in these patients.

Secondary

* Determine the overall survival and time to progression in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive pemetrexed disodium IV over 10 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Patients also receive cyanocobalamin intramuscularly once every 9 weeks and folic acid orally once daily beginning on day -6 and continuing until 3 weeks after the completion of study therapy. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 24-46 patients will be accrued for this study within 15 -18 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed cancer of the urothelium (renal pelvis, ureter, bladder, or urethra)

  * Any of the following types:

    * Transitional cell carcinoma (TCC)
    * Mixed histologies containing a component of TCC
    * Non-TCC of the urothelium (renal pelvis, ureter, bladder, or urethra)
* Progressing regional or metastatic disease
* Measurable disease
* No clinical evidence of CNS metastases
* No evidence of clinically significant (by physical exam or plain film) third-space fluid collections (pleural effusions or ascites)

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* Granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 9 g/dL

Hepatic

* AST no greater than 3 times upper limit of normal (ULN)
* Bilirubin no greater than 1.5 times ULN

Renal

* Creatinine clearance at least 45 mL/min

Cardiovascular

* No history of severe cardiovascular disease (i.e., American Heart Association class III or IV heart disease)
* No uncontrolled congestive heart failure
* No ventricular dysrhythmias

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No active unresolved infection
* No other prior malignancy unless curatively treated and disease free for an appropriate (disease-specific) period of time
* Able and willing to receive folic acid and cyanocobalamin supplementation

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior systemic biologic response modifier therapy

Chemotherapy

* No prior systemic chemotherapy for metastatic disease
* More than 1 year since prior neoadjuvant or adjuvant chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* At least 4 weeks since prior radiotherapy and recovered
* No prior pelvic radiotherapy
* No concurrent radiotherapy

Surgery

* At least 4 weeks since prior major surgery and recovered

Other

* More than 7 days since prior parenteral antibiotics
* No salicylates for 2 days before, during, and for 2 days after administration of pemetrexed disodium
* No nonsteroidal anti-inflammatory drugs for at least 5 days before, during, and for 2 days after administration of pemetrexed disodium

Primary outcomes:
measure: Response as measured by RECIST criteria
timeFrame: Assessed every 6 weeks
Secondary outcomes:
measure: Time to disease progression
timeFrame: Assessed every 6 weeks
measure: Overall survival
timeFrame: Assessed every 3 months for 2 years, then every 6 months for 3 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Aurora Presbyterian Hospital
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Incorporated
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Hope Cancer Care Center at Longmont United Hospital
state: Colorado
city: Pueblo
country: United States
facility: St. Mary-Corwin Regional Medical Center
state: Colorado
city: Thornton
country: United States
facility: North Suburban Medical Center
state: Colorado
city: New Haven
country: United States
facility: Yale Comprehensive Cancer Center at Yale University School of Medicine
state: Connecticut
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Wilmington
country: United States
facility: St. Francis Hospital
state: Delaware
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Lakeland
country: United States
facility: Watson Clinic, LLC
state: Florida
city: Athens
country: United States
facility: Hematology and Oncology of Northeast Georgia
state: Georgia
city: Augusta
country: United States
facility: MBCCOP-Medical College of Georgia Cancer Center
state: Georgia
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology Hematology Associates, Limited - West
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Plymouth
country: United States
facility: Saint Joseph Regional Medical Center - Plymouth Campus
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, P.C.
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, P.A. - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, P.A. - Parsons
state: Kansas
city: Pratt
country: United States
facility: Pratt Cancer Center of Kansas
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, P.A.
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, P.A. - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Elkton
country: United States
facility: Union Hospital Cancer Center at Union Hospital
state: Maryland
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Iron Mountain
country: United States
facility: Green Bay Oncology, Limited - Iron Mountain
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Bemidji
country: United States
facility: MeritCare Clinic - Bemidji
state: Minnesota
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Duluth
country: United States
facility: Miller-Dwan Medical Center
state: Minnesota
city: Duluth
country: United States
facility: St. Mary's - Duluth Clinic Cancer Center
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Litchfield
country: United States
facility: Meeker County Memorial Hospital
state: Minnesota
city: Maplewood
country: United States
facility: St. John's Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Medical Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Health Services
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: St. Joseph's Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Cancer Center
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Woodwinds Hospital
state: Minnesota
city: Camden
country: United States
facility: Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees
state: New Jersey
city: East Orange
country: United States
facility: Veterans Affairs Medical Center - East Orange
state: New Jersey
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: Hamilton
country: United States
facility: Cancer Institute of New Jersey at Hamilton
state: New Jersey
city: Marlton
country: United States
facility: Fox Chase Virtua Health Cancer Program - Marlton
state: New Jersey
city: Montclair
country: United States
facility: Mountainside Hospital Cancer Center
state: New Jersey
city: Morristown
country: United States
facility: Carol G. Simon Cancer Center at Morristown Memorial Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Bronx
country: United States
facility: Our Lady of Mercy Medical Center Comprehensive Cancer Center
state: New York
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Fargo
country: United States
facility: MeritCare Medical Group
state: North Dakota
city: Canton
country: United States
facility: Aultman Hospital Cancer Center at Aultman Health Foundation
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth's Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Bethlehem
country: United States
facility: St. Luke's Hospital Cancer Center
state: Pennsylvania
city: Lemoyne
country: United States
facility: Central Pennsylvania Hematology and Medical Oncology Associates, P. C.
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase-Temple Cancer Center
state: Pennsylvania
city: West Chester
country: United States
facility: Chester County Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital and Medical Center
state: Pennsylvania
city: Aiken
country: United States
facility: Cancer Care Institute of Carolina at Aiken Regional Medical Centers
state: South Carolina
city: Sioux Falls
country: United States
facility: Sioux Valley Hospital and University of South Dakota Medical Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera McKennan Hospital and University Health Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center
state: South Dakota
city: Chattanooga
country: United States
facility: Erlanger Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Manitowoc
country: United States
facility: Cancer Care Center at Holy Family Memorial Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: The Cleveland Clinic
name: Robert Dreicer, MD, FACP
role: STUDY_CHAIR
References:
citation: Dreicer R, Li H, Cooney MM, Wilding G, Roth BJ; Eastern Cooperative Oncology Group. Phase 2 trial of pemetrexed disodium and gemcitabine in advanced urothelial cancer (E4802): a trial of the Eastern Cooperative Oncology Group. Cancer. 2008 Jun 15;112(12):2671-5. doi: 10.1002/cncr.23503.
citation: Li S, Dreicer R, Roth B, et al.: Phase II trial of pemetrexed disodium and gemcitabine in advanced carcinoma of the urothelium (E4802): a trial of the Eastern Cooperative Oncology Group. [Abstract] J Clin Oncol 25 (Suppl 18): A-5079, 254s, 2007.