S0809: Capecitabine, Gemcitabine, and RT in Patients w/Cholangiocarcinoma of the Gallbladder or Bile Duct

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as capecitabine and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving more than one drug (combination chemotherapy) together with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving capecitabine together with gemcitabine followed by capecitabine and radiation therapy works in treating patients with cholangiocarcinoma of the gallbladder or bile duct.

Detailed Description
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OBJECTIVES: To estimate the stratum-specific (R0 and R1) and overall 2-year survival probabilities of patients with extrahepatic cholangiocarcinoma treated with adjuvant chemotherapy comprising capecitabine and gemcitabine hydrochloride, followed by capecitabine and radiotherapy. (R0 stratum closed as of 12-15-11) To estimate the 2-year stratum-specific and overall disease-free survival and local disease-free survival of patients treated with this regimen. To assess the frequency and severity of toxicity in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients are stratified according to margin of resection (negative [R0] vs microscopically positive [R1]). (R0 stratum closed as of 12-15-11) Adjuvant chemotherapy: Patients receive oral capecitabine every 12 hours on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Chemoradiotherapy: Beginning in week 13, patients receive oral capecitabine every 12 hours on days 1-7. Patients also undergo concurrent three-dimensional or intensity-modulated radiotherapy on days 1-5. Treatment repeats weekly for 5-6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy patients are followed periodically for up to 5 years.

Official Title
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A Phase II Trial of Adjuvant Capecitabine/Gemcitabine Chemotherapy Followed By Concurrent Capecitabine and Radiotherapy in Extrahepatic Cholangiocarcinoma (EHCC)

Conditions
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Extrahepatic Bile Duct Cancer, Gallbladder Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: gemcitabine hydrochloride
* Radiation: 3-dimensional conformal radiation therapy
* Radiation: intensity-modulated radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histopathologically confirmed extrahepatic cholangiocarcinoma of the gallbladder or bile duct, meeting at least 1 of the following criteria: Pathological T2-4 disease Pathological N1 disease Positive margins (any T or N ) Must have undergone potentially curative radical resection with negative (R0) or microscopically positive (R1) margins within the past 56 days and recovered (R0 stratum closed as of 12-15-11) No distant metastatic disease as indicated by a CT scan or MRI of the chest, abdomen, and pelvis within the past 42 days Positive resected regional lymph nodes allowed No ampullary cancer PATIENT CHARACTERISTICS: Zubrod performance status 0-1 ANC > 1,500/μL Platelet count > 100,000/μL Serum creatinine < 1.5 mg/dL Total bilirubin < 1.5 times upper limit of normal (ULN) SGOT or SGPT < 2.5 times ULN Not pregnant or nursing Fertile patients must use effective contraception Able to swallow enteral medications and no requirement for a feeding tube No intractable nausea or vomiting No gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, requirement for IV alimentation, prior surgical procedures affecting absorptions. or uncontrolled inflammatory GI disease (e.g., Crohn disease, ulcerative colitis) No uncontrolled intercurrent illness including but not limited to any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Myocardial infarction or cerebrovascular accident within the past 3 months Uncontrolled diarrhea Psychiatric illness or social situations that would limit compliance with study requirements No prior malignancy except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer, or other cancer from which the patient has been disease-free for 5 years PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy or radiotherapy for this disease No prior upper abdominal radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Adjuvant Chemo+ Chemoradiotherapy<br>Adjuvant Chemotherapy Capecitabine, 1500 mg/m^2/day, PO, Every 12 hrs on Days 1-14 of each cycle Gemcitabine hydrochloride, 1000 mg/m^2, IV, Days 1 & 8 of each cycle Chemoradiotherapy -Capecitabine, 1330 mg/m^2/day, PO, Every 12 hrs, 7 days per week beginning the first day of RT and finishing the last day of RT Radiation (RT): 3-dimensional conformal radiation therapy - 4,500 cGy over 5 weeks (5 days/week) in 180 cGy/fraction + 900 cGy during week 1 in 180 cGy fractions. intensity-modulated radiation therapy: 4,500 cGy over 5 weeks (5 days/week) in 180 cGy/fraction + 5,250 cGy in 210 cGy/fraction for a total of 25 fractions. | Drug: capecitabine<br>* Adjuvant chemotherapy: 1500 mg/m^2/day, PO, Every 12 hrs on Days 1-14 of each cycle Chemoradiotherapy: 1330 mg/m^2/day, PO, Every 12 hrs, 7 days per week beginning the first day of RT and finishing the last day of RT<br>* Other names: NSC-712807;Drug: gemcitabine hydrochloride<br>* 1000 mg/m^2, IV, Days 1 & 8 of each cycle<br>* Other names: NSC-619927;Radiation: 3-dimensional conformal radiation therapy<br>* 4,500 cGy over 5 weeks (5 days/week) in 180 cGy/fraction + 900 cGy during week 1 in 180 cGy fractions.<br>* Other names: 3D radiotherapy;Radiation: intensity-modulated radiation therapy<br>* 4,500 cGy over 5 weeks (5 days/week) in 180 cGy/fraction + 5,250 cGy in 210 cGy/fraction for a total of 25 fractions.<br>* Other names: IMRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stratum-specific (R0 and R1) 2-year Overall Survival | Time to death is calculated from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. | Up to 2 years from registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Only adverse events that are possibly, probably or definitely related to study drug are reported. | Up to 5 years | 
| 2-year Overall Survival for All Patients | Time to death is calculated from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. | Up to 2 years from registration | 
| 2-year Stratum-specific Disease-free Survival | Disease-free survival is calculated from date of registration to date of first documentation of relapse or death due to any cause. Patients last known to be alive are censored at date of last contact. | Up to 2 years from registration | 
| 2-year Disease-free Survival in All Patients | Disease-free survival is calculated from date of registration to date of first documentation of relapse or death due to any cause. Patients last known to be alive are censored at date of last contact. | Up to 2 years from registration | 
| 2-year Stratum-specific Local Relapse Rate | Local relapse is any evidence of new disease within the primary tumor bed or the regional (retroperitoneal, celiac, and portal vein nodes) lymphatics (these areas are to be encompassed within the radiation fields). | Up to 2 years from registration | 
| 2-year Overall Local Relapse Rate | Local relapse is any evidence of new disease within the primary tumor bed or the regional (retroperitoneal, celiac, and portal vein nodes) lymphatics (these areas are to be encompassed within the radiation fields). | Up to 2 years from registration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cholangiocarcinoma of the extrahepatic bile duct, cholangiocarcinoma of the gallbladder, localized extrahepatic bile duct cancer, localized gallbladder cancer, unresectable extrahepatic bile duct cancer, unresectable gallbladder cancer, metastatic extrahepatic bile duct cancer, metastatic gallbladder cancer