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

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00033540
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 57
• Locations: 112
• Arm: 1
• Duration (Months): 94
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Extrahepatic Bile Duct Cancer; Gallbladder Cancer	Drug: capecitabine; Drug: gemcitabine hydrochloride	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Gemcitabine (NSC-613327) and Capecitabine (NSC-712807) in Patients With Unresectable or Metastatic Gallbladder or Cholangiocarcinoma
• Study Start Date: Sep 1, 2003
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. Response [Patients assessed at least every six weeks while on protocol treatment]

   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.

Secondary Outcome Measures

1. Overall Survival [All patients will be followed until death or three years after registration, whichever is first.]

   Measured from time of registration to death, or last contact date

2. Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [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.]

   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.

3. Accrual of Patients With This Disease Site [1-20 months]

   Only eligible patients who received treatment were evaluable for response and survival outcomes.

4. Median Survival Time for Participants With Relevant Biologic Markers [All patients will be followed until death or three years after registration, whichever is first.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mobile Infirmary Medical Center	Mobile	Alabama	United States	36652-2144
2	Providence Alaska Medical Center	Anchorage	Alaska	United States	99519-6604
3	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Alta Bates Comprehensive Cancer Center	Berkeley	California	United States	94704
5	North Bay Cancer Center	Fairfield	California	United States	94533
6	Marin Cancer Institute at Marin General Hospital	Greenbrae	California	United States	94904
7	Sutter Health Western Division Cancer Research Group	Greenbrae	California	United States	94904
8	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90033
9	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California	United States	92868
10	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado	United States	80010
11	Memorial Hospital Cancer Center	Colorado Springs	Colorado	United States	80909
12	West Florida Regional Medical Center	Pensacola	Florida	United States	32514-6088
13	Hematology Oncology Associates of Eastern Idaho	Idaho Falls	Idaho	United States	83404
14	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
15	Cancer Care Center at St. Francis Hospital	Indianapolis	Indiana	United States	46237
16	South Central Kansas Regional Medical Center	Arkansas City	Kansas	United States	67005
17	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
18	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
19	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7353
20	Cancer Center of Kansas - Kingman	Kingman	Kansas	United States	67068
21	Southwest Medical Center	Liberal	Kansas	United States	67901
22	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
23	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
24	Pratt Cancer Center of Kansas	Pratt	Kansas	United States	67124
25	Salina Regional Health Center	Salina	Kansas	United States	67401
26	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67402
27	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
28	Associates in Womens Health	Wichita	Kansas	United States	67203
29	Cancer Center of Kansas, P.A. - Wichita	Wichita	Kansas	United States	67214-3728
30	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
31	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
32	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
33	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0084
34	Louisiana State University Health Sciences Center - Monroe	Monroe	Louisiana	United States	71210
35	Tulane Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana	United States	70112
36	Cancer Treatment Center at Christus Schumpert St. Mary Place	Shreveport	Louisiana	United States	71101-0000
37	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana	United States	71101-4295
38	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana	United States	71130-3932
39	Cancer Center at Thibodaux Regional Medical Center	Thibodaux	Louisiana	United States	70302-1118
40	Battle Creek Health System	Battle Creek	Michigan	United States	49016
41	Mecosta County General Hospital	Big Rapids	Michigan	United States	49307
42	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan	United States	48202
43	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
44	Lacks Cancer Center at Saint Mary's Mercy Medical Center	Grand Rapids	Michigan	United States	49503
45	Spectrum Health Cancer Care - Butterworth Campus	Grand Rapids	Michigan	United States	49503
46	Metropolitan Hospital	Grand Rapids	Michigan	United States	49506
47	Spectrum Health Hospital - Blodgett Campus	Grand Rapids	Michigan	United States	49506
48	Holland Community Hospital	Holland	Michigan	United States	49423
49	Hackley Hospital	Muskegon	Michigan	United States	49443-3302
50	Northern Michigan Hospital	Petoskey	Michigan	United States	49770
51	Munson Medical Center	Traverse City	Michigan	United States	49684
52	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
53	St. Francis Medical Center	Cape Girardeau	Missouri	United States	63701
54	CCOP - Kansas City	Kansas City	Missouri	United States	64131
55	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
56	Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
57	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
58	St. John's Regional Health Center	Springfield	Missouri	United States	65804-2263
59	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
60	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
61	Great Falls Clinic	Great Falls	Montana	United States	59403
62	Sletten Regional Cancer Institute	Great Falls	Montana	United States	59405
63	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico	United States	87108-5138
64	Adirondack Cancer Care	Glens Falls	New York	United States	12801
65	Orange Regional Medical Center - Horton Campus	Middletown	New York	United States	10940-4199
66	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
67	Mission Hospitals - Memorial Campus	Asheville	North Carolina	United States	28801
68	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
69	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
70	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27533
71	Cancer Center at Iredell Memorial Hospital	Statesville	North Carolina	United States	28687-1828
72	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
73	University Hospitals Ireland Cancer Center at Mercy Medical Center	Canton	Ohio	United States	44708
74	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
75	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio	United States	45220-2288
76	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267-0501
77	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195-9001
78	CCOP - Columbus	Columbus	Ohio	United States	43206
79	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
80	Grandview Hospital	Dayton	Ohio	United States	45405
81	Good Samaritan Hospital	Dayton	Ohio	United States	45406-1891
82	Miami Valley Hospital	Dayton	Ohio	United States	45409
83	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
84	CCOP - Dayton	Dayton	Ohio	United States	45429
85	Grady Memorial Hospital	Delaware	Ohio	United States	43015
86	Community Oncology Group - Independence	Independence	Ohio	United States	44131
87	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
88	Fairfield Medical Center	Lancaster	Ohio	United States	43130
89	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750-1635
90	Middletown Regional Hospital	Middletown	Ohio	United States	45044-4898
91	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055-2899
92	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
93	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
94	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
95	Cancer Institute at Oregon Health and Science University	Portland	Oregon	United States	97201-3098
96	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
97	McLeod Regional Medical Center	Florence	South Carolina	United States	29501
98	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
99	CCOP - Greenville	Greenville	South Carolina	United States	29615
100	Veterans Affairs Medical Center - Amarillo	Amarillo	Texas	United States	79106
101	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
102	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112-5550
103	Memorial Hospital of Martinsville and Henry County	Martinsville	Virginia	United States	24115-4788
104	St. Joseph Hospital Community Cancer Center	Bellingham	Washington	United States	98225
105	Harborview Medical Center	Seattle	Washington	United States	98104
106	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98104
107	Veterans Affairs Medical Center - Seattle	Seattle	Washington	United States	98108
108	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024
109	Group Health Central Hospital	Seattle	Washington	United States	98112
110	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
111	Central Washington Hospital	Wenatchee	Washington	United States	98801
112	Wenatchee Valley Clinic	Wenatchee	Washington	United States	98801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Syma Iqbal, MD, University of Southern California
• Study Chair: Heinz-Josef Lenz, MD, University of Southern California

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00033540
• Other Study ID Numbers: CDR0000069299; S0202; U10CA032102
• First Posted: Jan 27, 2003
• Last Update Posted: Sep 12, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Southwest Oncology Group: 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
• Additional relevant MeSH terms: Cholangiocarcinoma; Gallbladder Neoplasms; Bile Duct Neoplasms; Gemcitabine; Capecitabine

Study Results

Participant Flow

Arm/Group Title	Capecitabine + Gemcitabine
Arm/Group Description	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
Period Title: Overall Study
STARTED	57
Eligible	54
Eligible and Began Protocol Therapy	52
COMPLETED	0
NOT COMPLETED	57

Baseline Characteristics

Arm/Group Title	Capecitabine + Gemcitabine
Arm/Group Description	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
Overall Participants	52
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58.8
Sex: Female, Male (Count of Participants)
Female	26 50%
Male	26 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 7.7%
Not Hispanic or Latino	47 90.4%
Unknown or Not Reported	1 1.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.9%
Asian	6 11.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 11.5%
White	37 71.2%
More than one race	0 0%
Unknown or Not Reported	2 3.8%

Outcome Measures

1. Primary Outcome

Title	Response
Description	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.
Time Frame	Patients assessed at least every six weeks while on protocol treatment

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in assessing response estimates.

Arm/Group Title	Capecitabine + Gemcitabine
Arm/Group Description	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
Measure Participants	52
Confirmed Partial Response	7 13.5%
Unconfirmed Partial Response	6 11.5%
Stable Disease	12 23.1%
Progression	15 28.8%
Symptomatic Deterioration	3 5.8%
Early Death	1 1.9%
Inadequate Assessment	8 15.4%

2. Secondary Outcome

Title	Overall Survival
Description	Measured from time of registration to death, or last contact date
Time Frame	All patients will be followed until death or three years after registration, whichever is first.

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in assessing response estimates.

Arm/Group Title	Capecitabine + Gemcitabine
Arm/Group Description	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
Measure Participants	52
Median (95% Confidence Interval) [months]	7

3. Secondary Outcome

Title	Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Eligible patients who received any treatment and were assessed for toxicity were included in the adverse event summaries. 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.

Arm/Group Title	Gemcitabine and Capecitabine
Arm/Group Description	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
Measure Participants	51
ALT, SGPT (serum glutamic pyruvic transaminase)	1 1.9%
AST,SGOT (serum glutamic oxaloacetic transaminase)	5 9.6%
Albumin, serum-low (hypoalbuminemia)	1 1.9%
Alkaline phosphatase	5 9.6%
Anorexia	2 3.8%
Ascites (non-malignant)	1 1.9%
Bilirubin (hyperbilirubinemia)	4 7.7%
Constipation	1 1.9%
Creatinine	1 1.9%
Dehydration	3 5.8%
Diarrhea	1 1.9%
Dysphagia (difficulty swallowing)	1 1.9%
Fatigue (asthenia, lethargy, malaise)	8 15.4%
Hemoglobin	6 11.5%
Hemolysis	1 1.9%
Hemorrhage, GI - Esophagus	1 1.9%
Infection w/Grade 3-4 neutrophils - Upper airway	1 1.9%
Infection with normal ANC or Grade 1-2 neutrophils	1 1.9%
Leukocytes (total WBC)	9 17.3%
Mucositis/stomatitis (clinical exam) - Oral cavity	1 1.9%
Mucositis/stomatitis (function/symp)-Oral cavity	1 1.9%
Muscle weakness (not due to neuropathy)	1 1.9%
Nausea	3 5.8%
Neutrophils/granulocytes (ANC/AGC)	16 30.8%
Pain - Abdomen NOS	2 3.8%
Pain - Joint	1 1.9%
Pain - Muscle	1 1.9%
Pain - Tumor pain	1 1.9%
Platelets	12 23.1%
Potassium, serum-low (hypokalemia)	2 3.8%
Rash: hand-foot skin reaction	4 7.7%
Supraventricular nodal arrhythmia	1 1.9%
Thrombosis/thrombus/embolism	1 1.9%
Vomiting	2 3.8%

4. Secondary Outcome

Title	Accrual of Patients With This Disease Site
Description	Only eligible patients who received treatment were evaluable for response and survival outcomes.
Time Frame	1-20 months

Outcome Measure Data

Analysis Population Description

Patients with advanced disease accrued between September 2003 to April 2005

Arm/Group Title	Capecitabine + Gemcitabine
Arm/Group Description	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
Measure Participants	57
Eligible	54 103.8%
Eligible and Analyzable	52 100%

5. Secondary Outcome

Title	Median Survival Time for Participants With Relevant Biologic Markers
Description	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.
Time Frame	All patients will be followed until death or three years after registration, whichever is first.

Outcome Measure Data

Analysis Population Description

Eligible patients who received genotyping were included in this analysis.

Arm/Group Title	Capecitabine + Gemcitabine
Arm/Group Description	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
Measure Participants	22
TS 3' +/+ (N=14)	7
TS 3' +/- (N=6)	7
TS 3' -/- (N=2)	9
TS 5' Low functional significance (N=16)	9
TS 5' Intermediate functional significance (N=16)	7
MTHFR C677T - C/C (N=11)	6
MTHFR C677T - C/T (N=11)	7
MTHFR A1298C - A/A (N=11)	7
MTHFR A1298C - A/C (N=8)	4
MTHFR A1298C - C/C (N=3)	9
RRMI G/A - G/G (N=9)	7
RRMI G/A - G/A (N=10)	9
RRMI G/A - A/A (N=3)	5
CDA A79C - A/A (N=8)	4
CDA A79C - A/C (N=12)	7
CDA A79C - C/C (N=1)	NA

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	One patient went off study prior to any toxicity assessments and is not evaluable for toxicities.
Arm/Group Title	Gemcitabine and Capecitabine
Arm/Group Description	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
All Cause Mortality
	Gemcitabine and Capecitabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine and Capecitabine
	Affected / at Risk (%)	# Events
Total	7/51 (13.7%)
General disorders
Constitutional Symptoms-Other (Specify)	2/51 (3.9%)
Hepatobiliary disorders
Hepatobiliary/Pancreas-Biliary obstruction	1/51 (2%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	1/51 (2%)
Investigations
Bilirubin (hyperbilirubinemia)	1/51 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - Disease progression NOS	3/51 (5.9%)
Other (Not Including Serious) Adverse Events
	Gemcitabine and Capecitabine
	Affected / at Risk (%)	# Events
Total	51/51 (100%)
Blood and lymphatic system disorders
Hemoglobin	42/51 (82.4%)
Eye disorders
Ocular surface disease	3/51 (5.9%)
Gastrointestinal disorders
Ascites (non-malignant)	4/51 (7.8%)
Constipation	21/51 (41.2%)
Diarrhea	17/51 (33.3%)
Heartburn/dyspepsia	4/51 (7.8%)
Mucositis/stomatitis (clinical exam) - Oral cavity	11/51 (21.6%)
Mucositis/stomatitis (functional/symp) - Oral cav	6/51 (11.8%)
Nausea	32/51 (62.7%)
Pain - Abdomen NOS	18/51 (35.3%)
Vomiting	19/51 (37.3%)
General disorders
Edema: limb	12/51 (23.5%)
Fatigue (asthenia, lethargy, malaise)	44/51 (86.3%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L	15/51 (29.4%)
Injection site reaction/extravasation changes	3/51 (5.9%)
Pain-Other (Specify)	4/51 (7.8%)
Rigors/chills	10/51 (19.6%)
Hepatobiliary disorders
Liver dysfunction/failure (clinical)	7/51 (13.7%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Bladder	4/51 (7.8%)
Inf w/normal ANC or Gr 1-2 neutrophils - Skin	3/51 (5.9%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	12/51 (23.5%)
AST, SGOT	39/51 (76.5%)
Alkaline phosphatase	36/51 (70.6%)
Bilirubin (hyperbilirubinemia)	13/51 (25.5%)
Creatinine	3/51 (5.9%)
GGT (gamma-glutamyl transpeptidase)	3/51 (5.9%)
Leukocytes (total WBC)	29/51 (56.9%)
Neutrophils/granulocytes (ANC/AGC)	30/51 (58.8%)
Platelets	29/51 (56.9%)
Weight loss	8/51 (15.7%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	13/51 (25.5%)
Anorexia	14/51 (27.5%)
Calcium, serum-low (hypocalcemia)	7/51 (13.7%)
Dehydration	4/51 (7.8%)
Glucose, serum-high (hyperglycemia)	18/51 (35.3%)
Potassium, serum-high (hyperkalemia)	3/51 (5.9%)
Potassium, serum-low (hypokalemia)	5/51 (9.8%)
Sodium, serum-low (hyponatremia)	9/51 (17.6%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - Extrem-lower	3/51 (5.9%)
Muscle weakness, not d/t neuropathy - body/general	3/51 (5.9%)
Pain - Back	8/51 (15.7%)
Pain - Extremity-limb	3/51 (5.9%)
Pain - Joint	4/51 (7.8%)
Pain - Muscle	4/51 (7.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - Tumor pain	14/51 (27.5%)
Nervous system disorders
Neuropathy: sensory	5/51 (9.8%)
Pain - Head/headache	7/51 (13.7%)
Taste alteration (dysgeusia)	4/51 (7.8%)
Psychiatric disorders
Insomnia	5/51 (9.8%)
Mood alteration - anxiety	4/51 (7.8%)
Mood alteration - depression	3/51 (5.9%)
Respiratory, thoracic and mediastinal disorders
Cough	5/51 (9.8%)
Dyspnea (shortness of breath)	13/51 (25.5%)
Pleural effusion (non-malignant)	3/51 (5.9%)
Skin and subcutaneous tissue disorders
Dry skin	3/51 (5.9%)
Hair loss/Alopecia (scalp or body)	12/51 (23.5%)
Nail changes	6/51 (11.8%)
Pruritus/itching	10/51 (19.6%)
Rash/desquamation	14/51 (27.5%)
Rash: hand-foot skin reaction	11/51 (21.6%)
Vascular disorders
Thrombosis/thrombus/embolism	3/51 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.