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

Gallbladder Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00033540
• Other study ID #: CDR0000069299
• Secondary ID: S0202U10CA032102
• Status: Completed
• Phase: Phase 2
• First received: April 9, 2002
• Last updated: September 24, 2012
• Start date: September 2003
• Est. completion date: July 2011

Study information

• Verified date: September 2012
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: July 2011
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bile Duct Neoplasms
• Cholangiocarcinoma
• Extrahepatic Bile Duct Cancer
• Gallbladder Cancer
• Gallbladder Neoplasms

Intervention

Drug:
• capecitabine
650 mg/m^2 twice daily (BID), by mouth (PO) at 12 hour intervals, Days 1-14, every 21 days
• gemcitabine hydrochloride
1000 mg/m^2, intravenous (IV) over 100 minutes, Days 1,8, every 21 days

Locations

Country	Name	City	State
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	Veterans Affairs Medical Center - Amarillo	Amarillo	Texas
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	South Central Kansas Regional Medical Center	Arkansas City	Kansas
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado
United States	Battle Creek Health System	Battle Creek	Michigan
United States	St. Joseph Hospital Community Cancer Center	Bellingham	Washington
United States	Alta Bates Comprehensive Cancer Center	Berkeley	California
United States	Mecosta County General Hospital	Big Rapids	Michigan
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	University Hospitals Ireland Cancer Center at Mercy Medical Center	Canton	Ohio
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri
United States	St. Francis Medical Center	Cape Girardeau	Missouri
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Memorial Hospital Cancer Center	Colorado Springs	Colorado
United States	CCOP - Columbus	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	North Bay Cancer Center	Fairfield	California
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Adirondack Cancer Care	Glens Falls	New York
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Mercy Medical Center	Grand Rapids	Michigan
United States	Metropolitan Hospital	Grand Rapids	Michigan
United States	Spectrum Health Cancer Care - Butterworth Campus	Grand Rapids	Michigan
United States	Spectrum Health Hospital - Blodgett Campus	Grand Rapids	Michigan
United States	Great Falls Clinic	Great Falls	Montana
United States	Sletten Regional Cancer Institute	Great Falls	Montana
United States	Marin Cancer Institute at Marin General Hospital	Greenbrae	California
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	Bon Secours St. Francis Health System	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Holland Community Hospital	Holland	Michigan
United States	Hematology Oncology Associates of Eastern Idaho	Idaho Falls	Idaho
United States	Community Oncology Group - Independence	Independence	Ohio
United States	Cancer Care Center at St. Francis Hospital	Indianapolis	Indiana
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas - Kingman	Kingman	Kansas
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Southwest Medical Center	Liberal	Kansas
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Memorial Hospital of Martinsville and Henry County	Martinsville	Virginia
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	Middletown Regional Hospital	Middletown	Ohio
United States	Orange Regional Medical Center - Horton Campus	Middletown	New York
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Louisiana State University Health Sciences Center - Monroe	Monroe	Louisiana
United States	Hackley Hospital	Muskegon	Michigan
United States	Tulane Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California
United States	West Florida Regional Medical Center	Pensacola	Florida
United States	Northern Michigan Hospital	Petoskey	Michigan
United States	Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Pratt Cancer Center of Kansas	Pratt	Kansas
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Cancer Treatment Center at Christus Schumpert St. Mary Place	Shreveport	Louisiana
United States	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Cancer Center at Iredell Memorial Hospital	Statesville	North Carolina
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Cancer Center at Thibodaux Regional Medical Center	Thibodaux	Louisiana
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Central Washington Hospital	Wenatchee	Washington
United States	Wenatchee Valley Clinic	Wenatchee	Washington
United States	Associates in Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas, P.A. - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Iqbal S, et al.: SWOG S0202: a phase II trial of gemcitabine and capecitabine in patients (pts) with unresectable or metastatic gallbladder cancer or cholangiocarcinoma. [Abstract] J Clin Oncol 24 (Suppl 18): A-4134, 2006.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	No
Secondary	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.	Yes
Secondary	Accrual of Patients With This Disease Site	Only eligible patients who received treatment were evaluable for response and survival outcomes.	1-20 months	No
Secondary	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.	No