Clinical trial NCT00033540: S0202 Gemcitabine and Capecitabine for Unresectable Locally Advanced Metastatic Gallbladder Cancer or Cholangiocarcinoma
Official title: A Phase II Trial of Gemcitabine (NSC-613327) and Capecitabine (NSC-712807) in Patients With Unresectable or Metastatic Gallbladder or Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Keywords: unresectable gallbladder cancer
recurrent gallbladder cancer
unresectable extrahepatic bile duct cancer
recurrent extrahepatic bile duct cancer
adenocarcinoma of the gallbladder
adenocarcinoma with squamous metaplasia of the gallbladder
squamous cell carcinoma of the gallbladder
adenocarcinoma of the extrahepatic bile duct
cholangiocarcinoma of the gallbladder
cholangiocarcinoma of the extrahepatic bile duct
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine with capecitabine in treating patients who have locally advanced or metastatic gallbladder cancer or cholangiocarcinoma.

Detailed description: OBJECTIVES:

* Determine the response rates (confirmed complete and partial responses) in patients with unresectable, locally advanced or metastatic gallbladder cancer or cholangiocarcinoma treated with gemcitabine and capecitabine.
* Determine the overall survival of patients treated with this regimen.
* Determine the quantitative and qualitative toxic effects of this regimen in these patients.
* Determine the feasibility of accruing patients with these disease sites.
* Evaluate, preliminarily, relevant prognostic markers in these disease sites and the prognostic implications as predictors of survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 1-14 and gemcitabine IV over 100 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within approximately 10-20 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed gallbladder cancer or cholangiocarcinoma

  * Locally advanced or metastatic disease that is unresectable
  * Eligible subtypes:

    * Adenocarcinoma, intestinal type
    * Adenocarcinoma, not otherwise specified (NOS)
    * Papillary carcinoma
    * Clear cell adenocarcinoma
    * Mucinous carcinoma
    * Signet ring cell carcinoma
    * Squamous cell carcinoma
    * Adenosquamous carcinoma
    * Small cell carcinoma
    * Undifferentiated carcinoma
    * Carcinoma, NOS

OR

* Histologically confirmed adenocarcinoma of a metastatic site with clinical documentation\* of gallbladder or bile duct involvement and no evidence of another primary

NOTE: \*If clinical documentation of gallbladder or bile duct involvement is not possible due to removal of the organ, a clinically and/or radiographically consistent picture plus pathologic findings from the metastatic site consistent with cholangiocarcinoma are allowed

* Measurable disease located outside prior radiotherapy port
* No carcinoid tumors or sarcomas

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Zubrod 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Absolute granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 3 times upper limit of normal (ULN)
* Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT) no greater than 2.5 times ULN (5 times ULN if liver metastasis is present)

Renal:

* Creatinine clearance at least 30 mL/min

Cardiovascular:

* No clinically significant cardiac disease that is not well controlled by medication
* No congestive heart failure
* No symptomatic coronary artery disease
* No cardiac arrhythmias
* No myocardial infarction within the past 12 months

Gastrointestinal:

* Able to swallow and/or receive medications via gastrostomy feeding tube
* No intractable nausea or vomiting
* No malabsorption syndrome

Other:

* No severe reaction to fluoropyrimidine therapy or known hypersensitivity to fluorouracil
* No other malignancy within the past 5 years except:

  * Adequately treated basal cell or squamous cell skin cancer
  * Carcinoma in situ of the cervix
  * Adequately treated stage I or II cancer currently in complete remission
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Prior neoadjuvant or adjuvant immunotherapy allowed provided therapy was completed at least 1 year before documented recurrence or metastatic disease
* No concurrent immunotherapy

Chemotherapy:

* Prior neoadjuvant or adjuvant chemotherapy or chemoradiotherapy allowed provided therapy was completed at least 1 year before documented recurrence or metastatic disease
* No other concurrent chemotherapy

Endocrine therapy:

* Prior neoadjuvant or adjuvant hormonal therapy allowed provided therapy was completed at least 1 year before documented recurrence or metastatic disease
* No concurrent hormonal therapy

Radiotherapy:

* See Disease Characteristics
* See Chemotherapy
* Recovered from prior radiotherapy
* Prior neoadjuvant or adjuvant radiotherapy allowed provided therapy was completed at least 1 year before documented recurrence or metastatic disease
* No prior radiotherapy to 25% or more of bone marrow
* No concurrent radiotherapy except for palliation of metastatic sites not considered target lesions

Surgery:

* At least 2 weeks since prior surgery for this malignancy and recovered

Other:

* No prior treatment for metastatic disease
* No other concurrent therapy for this cancer

Primary outcomes:
measure: Response
timeFrame: Patients assessed at least every six weeks while on protocol treatment
Secondary outcomes:
measure: Overall Survival
timeFrame: All patients will be followed until death or three years after registration, whichever is first.
measure: Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
timeFrame: Patients were assessed for adverse events 3 weeks after starting treatment. Assessments for adverse events continued every 3 weeks for the duration of protocol treatment.
measure: Accrual of Patients With This Disease Site
timeFrame: 1-20 months
measure: Median Survival Time for Participants With Relevant Biologic Markers
timeFrame: All patients will be followed until death or three years after registration, whichever is first.
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Berkeley
country: United States
facility: Alta Bates Comprehensive Cancer Center
state: California
city: Fairfield
country: United States
facility: North Bay Cancer Center
state: California
city: Greenbrae
country: United States
facility: Marin Cancer Institute at Marin General Hospital
state: California
city: Greenbrae
country: United States
facility: Sutter Health Western Division Cancer Research Group
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
city: Colorado Springs
country: United States
facility: Memorial Hospital Cancer Center
state: Colorado
city: Pensacola
country: United States
facility: West Florida Regional Medical Center
state: Florida
city: Idaho Falls
country: United States
facility: Hematology Oncology Associates of Eastern Idaho
state: Idaho
city: Alton
country: United States
facility: Saint Anthony's Hospital at Saint Anthony's Health Center
state: Illinois
city: Indianapolis
country: United States
facility: Cancer Care Center at St. Francis Hospital
state: Indiana
city: Arkansas City
country: United States
facility: South Central Kansas Regional Medical Center
state: Kansas
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: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
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: McPherson
country: United States
facility: Cancer Center of Kansas - McPherson
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas - Newton
state: Kansas
city: Pratt
country: United States
facility: Pratt Cancer Center of Kansas
state: Kansas
city: Salina
country: United States
facility: Salina Regional Health Center
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. - 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: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Monroe
country: United States
facility: Louisiana State University Health Sciences Center - Monroe
state: Louisiana
city: New Orleans
country: United States
facility: Tulane Cancer Center at Tulane University Hospital and Clinic
state: Louisiana
city: Shreveport
country: United States
facility: Cancer Treatment Center at Christus Schumpert St. Mary Place
state: Louisiana
city: Shreveport
country: United States
facility: Veterans Affairs Medical Center - Shreveport
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center - Shreveport
state: Louisiana
city: Thibodaux
country: United States
facility: Cancer Center at Thibodaux Regional Medical Center
state: Louisiana
city: Battle Creek
country: United States
facility: Battle Creek Health System
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County General Hospital
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Mercy Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Cancer Care - Butterworth Campus
state: Michigan
city: Grand Rapids
country: United States
facility: Metropolitan Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospital - Blodgett Campus
state: Michigan
city: Holland
country: United States
facility: Holland Community Hospital
state: Michigan
city: Muskegon
country: United States
facility: Hackley Hospital
state: Michigan
city: Petoskey
country: United States
facility: Northern Michigan Hospital
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Cape Girardeau
country: United States
facility: Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
state: Missouri
city: Cape Girardeau
country: United States
facility: St. Francis Medical Center
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Saint Louis
country: United States
facility: Center for Cancer Care and Research
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Great Falls
country: United States
facility: Sletten Regional Cancer Institute
state: Montana
city: Albuquerque
country: United States
facility: Veterans Affairs Medical Center - Albuquerque
state: New Mexico
city: Glens Falls
country: United States
facility: Adirondack Cancer Care
state: New York
city: Middletown
country: United States
facility: Orange Regional Medical Center - Horton Campus
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Hospitals - Memorial Campus
state: North Carolina
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Statesville
country: United States
facility: Cancer Center at Iredell Memorial Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Regional Cancer Center at Forsyth Medical Center
state: North Carolina
city: Canton
country: United States
facility: University Hospitals Ireland Cancer Center at Mercy Medical Center
state: Ohio
city: Chillicothe
country: United States
facility: Adena Regional Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Veterans Affairs Medical Center - Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital Cancer Care
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Delaware
country: United States
facility: Grady Memorial Hospital
state: Ohio
city: Independence
country: United States
facility: Community Oncology Group - Independence
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Lancaster
country: United States
facility: Fairfield Medical Center
state: Ohio
city: Marietta
country: United States
facility: Strecker Cancer Center at Marietta Memorial Hospital
state: Ohio
city: Middletown
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Newark
country: United States
facility: Licking Memorial Cancer Care Program at Licking Memorial Hospital
state: Ohio
city: Springfield
country: United States
facility: Community Hospital of Springfield and Clark County
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Portland
country: United States
facility: Cancer Institute at Oregon Health and Science University
state: Oregon
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Greenville
country: United States
facility: Bon Secours St. Francis Health System
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Amarillo
country: United States
facility: Veterans Affairs Medical Center - Amarillo
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Martinsville
country: United States
facility: Memorial Hospital of Martinsville and Henry County
state: Virginia
city: Bellingham
country: United States
facility: St. Joseph Hospital Community Cancer Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: Veterans Affairs Medical Center - Seattle
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Group Health Central Hospital
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Wenatchee
country: United States
facility: Central Washington Hospital
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Clinic
state: Washington
Study officials:
affiliation: University of Southern California
name: Syma Iqbal, MD
role: STUDY_CHAIR
affiliation: University of Southern California
name: Heinz-Josef Lenz, MD
role: STUDY_CHAIR
References:
citation: Lurje G, Zhang W, Yang D, Groshen S, Hendifar AE, Husain H, Nagashima F, Chang HM, Fazzone W, Ladner RD, Pohl A, Ning Y, Iqbal S, El-Khoueiry A, Lenz HJ. Thymidylate synthase haplotype is associated with tumor recurrence in stage II and stage III colon cancer. Pharmacogenet Genomics. 2008 Feb;18(2):161-8. doi: 10.1097/FPC.0b013e3282f4aea6.
citation: Iqbal S, Rankin C, Lenz HJ, Gold PJ, Ahmad SA, El-Khoueiry AB, Messino MJ, Holcombe RF, Blanke CD. A phase II trial of gemcitabine and capecitabine in patients with unresectable or metastatic gallbladder cancer or cholangiocarcinoma: Southwest Oncology Group study S0202. Cancer Chemother Pharmacol. 2011 Dec;68(6):1595-602. doi: 10.1007/s00280-011-1657-1. Epub 2011 May 10.