S0202 Gemcitabine and Capecitabine for Unresectable Locally Advanced Metastatic Gallbladder Cancer or Cholangiocarcinoma

A Phase II Trial of Gemcitabine (NSC-613327) and Capecitabine (NSC-712807) in Patients With Unresectable or Metastatic Gallbladder or Cholangiocarcinoma

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.

Study Overview

• Status: Completed
• Conditions: Gallbladder Cancer; Extrahepatic Bile Duct Cancer
• Intervention / Treatment: Drug: capecitabine; Drug: gemcitabine hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Alaska
    • Anchorage, Alaska, United States, 99519-6604
      • Providence Alaska Medical Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Comprehensive Cancer Center
    • Fairfield, California, United States, 94533
      • North Bay Cancer Center
    • Greenbrae, California, United States, 94904
      • Sutter Health Western Division Cancer Research Group
    • Greenbrae, California, United States, 94904
      • Marin Cancer Institute at Marin General Hospital
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Hospital Cancer Center
  • Florida
    • Pensacola, Florida, United States, 32514-6088
      • West Florida Regional Medical Center
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Hematology Oncology Associates of Eastern Idaho
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Hospital at Saint Anthony's Health Center
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Cancer Care Center at St. Francis Hospital
  • Kansas
    • Arkansas City, Kansas, United States, 67005
      • South Central Kansas Regional Medical Center
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • Kansas City, Kansas, United States, 66160-7353
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • McPherson, Kansas, United States, 67460
      • Cancer Center of Kansas - McPherson
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Pratt, Kansas, United States, 67124
      • Pratt Cancer Center of Kansas
    • Salina, Kansas, United States, 67401
      • Salina Regional Health Center
    • Salina, Kansas, United States, 67402
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67203
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214-3728
      • Cancer Center of Kansas, P.A. - Wichita
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0084
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
  • Louisiana
    • Monroe, Louisiana, United States, 71210
      • Louisiana State University Health Sciences Center - Monroe
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center at Tulane University Hospital and Clinic
    • Shreveport, Louisiana, United States, 71130-3932
      • Louisiana State University Health Sciences Center - Shreveport
    • Shreveport, Louisiana, United States, 71101-4295
      • Veterans Affairs Medical Center - Shreveport
    • Shreveport, Louisiana, United States, 71101-0000
      • Cancer Treatment Center at Christus Schumpert St. Mary Place
    • Thibodaux, Louisiana, United States, 70302-1118
      • Cancer Center at Thibodaux Regional Medical Center
  • Michigan
    • Battle Creek, Michigan, United States, 49016
      • Battle Creek Health System
    • Big Rapids, Michigan, United States, 49307
      • Mecosta County General Hospital
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Mercy Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Cancer Care - Butterworth Campus
    • Grand Rapids, Michigan, United States, 49506
      • Metropolitan Hospital
    • Grand Rapids, Michigan, United States, 49506
      • Spectrum Health Hospital - Blodgett Campus
    • Holland, Michigan, United States, 49423
      • Holland Community Hospital
    • Muskegon, Michigan, United States, 49443-3302
      • Hackley Hospital
    • Petoskey, Michigan, United States, 49770
      • Northern Michigan Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
  • Missouri
    • Cape Girardeau, Missouri, United States, 63701
      • St. Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63141
      • Center for Cancer Care and Research
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
    • Springfield, Missouri, United States, 65804-2263
      • St. John's Regional Health Center
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Great Falls, Montana, United States, 59405
      • Sletten Regional Cancer Institute
    • Great Falls, Montana, United States, 59403
      • Great Falls Clinic
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108-5138
      • Veterans Affairs Medical Center - Albuquerque
  • New York
    • Glens Falls, New York, United States, 12801
      • Adirondack Cancer Care
    • Middletown, New York, United States, 10940-4199
      • Orange Regional Medical Center - Horton Campus
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals - Memorial Campus
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Cancer Center at Presbyterian Hospital
    • Goldsboro, North Carolina, United States, 27533
      • Wayne Memorial Hospital, Incorporated
    • Statesville, North Carolina, United States, 28687-1828
      • Cancer Center at Iredell Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Regional Cancer Center at Forsyth Medical Center
  • Ohio
    • Canton, Ohio, United States, 44708
      • University Hospitals Ireland Cancer Center at Mercy Medical Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45220-2288
      • Veterans Affairs Medical Center - Cincinnati
    • Cincinnati, Ohio, United States, 45267-0501
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195-9001
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Dayton, Ohio, United States, 45406-1891
      • Good Samaritan Hospital
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Independence, Ohio, United States, 44131
      • Community Oncology Group - Independence
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Marietta, Ohio, United States, 45750-1635
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Middletown, Ohio, United States, 45044-4898
      • Middletown Regional Hospital
    • Newark, Ohio, United States, 43055-2899
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • Springfield, Ohio, United States, 45505
      • Community Hospital of Springfield and Clark County
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Oregon
    • Portland, Oregon, United States, 97201-3098
      • Cancer Institute at Oregon Health and Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Florence, South Carolina, United States, 29501
      • McLeod Regional Medical Center
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29601
      • Bon Secours St. Francis Health System
  • Texas
    • Amarillo, Texas, United States, 79106
      • Veterans Affairs Medical Center - Amarillo
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84112-5550
      • Huntsman Cancer Institute at University of Utah
  • Virginia
    • Martinsville, Virginia, United States, 24115-4788
      • Memorial Hospital of Martinsville and Henry County
  • Washington
    • Bellingham, Washington, United States, 98225
      • St. Joseph Hospital Community Cancer Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Medical Center - Seattle
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98195-6043
      • University Cancer Center at University of Washington Medical Center
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Wenatchee, Washington, United States, 98801
      • Central Washington Hospital
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capecitabine + Gemcitabine; Capecitabine 650 mg/m^2 twice daily (BID), by mouth (PO) at 12 hour intervals, Days 1-14, every 21 days; Gemcitabine 1000 mg/m^2, intravenous (IV) over 100 minutes, Days 1, 8, every 21 days	Drug: capecitabine; 650 mg/m^2 twice daily (BID), by mouth (PO) at 12 hour intervals, Days 1-14, every 21 days; Other Names: Xeloda (NSC-712807); Drug: gemcitabine hydrochloride; 1000 mg/m^2, intravenous (IV) over 100 minutes, Days 1,8, every 21 days; Other Names: Gemzar (NSC-613327)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response	Complete Response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms. Normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.	Patients assessed at least every six weeks while on protocol treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Measured from time of registration to death, or last contact date	All patients will be followed until death or three years after registration, whichever is first.
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug	Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included. For each patient, worst grade of each event type is reported.	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.
Accrual of Patients With This Disease Site	Only eligible patients who received treatment were evaluable for response and survival outcomes.	1-20 months
Median Survival Time for Participants With Relevant Biologic Markers	To evaluate in a preliminary fashion relevant prognostic markers in gallbladder and cholangiocarcinoma which may have prognostic implications as predictors of survival. Overall survival measured from time of registration to death, or last contact date.	All patients will be followed until death or three years after registration, whichever is first.

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Syma Iqbal, MD, University of Southern California

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: April 9, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): September 12, 2017
• Last Update Submitted That Met QC Criteria: August 14, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: unresectable gallbladder cancer; recurrent gallbladder cancer; unresectable extrahepatic bile duct cancer; recurrent extrahepatic bile duct cancer; cholangiocarcinoma of the gallbladder; cholangiocarcinoma of the extrahepatic bile duct; adenocarcinoma of the gallbladder; adenocarcinoma of the extrahepatic bile duct; adenocarcinoma with squamous metaplasia of the gallbladder; squamous cell carcinoma of the gallbladder
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Gallbladder Diseases; Biliary Tract Diseases; Bile Duct Diseases; Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms; Bile Duct Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Capecitabine
• Other Study ID Numbers: CDR0000069299; U10CA032102 (U.S. NIH Grant/Contract); S0202 (Other Identifier: SWOG)