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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Extrahepatic Bile Duct Cancer, Gallbladder Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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