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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00789958

Enrollment

105

Registered

2008-11-13

Start date

2008-12-31

Completion date

2017-12-31

Last updated

2018-04-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Extrahepatic Bile Duct Cancer, Gallbladder Cancer

Keywords

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

Brief summary

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

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.

Interventions

DRUGcapecitabine

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

DRUGgemcitabine hydrochloride

1000 mg/m\^2, IV, Days 1 & 8 of each cycle

RADIATION3-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.

RADIATIONintensity-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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 120 Years

Healthy volunteers

Inclusion criteria

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

Design outcomes

Primary

Measure	Time frame	Description
Stratum-specific (R0 and R1) 2-year Overall Survival	Up to 2 years from registration	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.

Secondary

Measure	Time frame	Description
2-year Overall Survival for All Patients	Up to 2 years from registration	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.
2-year Stratum-specific Disease-free Survival	Up to 2 years from registration	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.
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug	Up to 5 years	Only adverse events that are possibly, probably or definitely related to study drug are reported.
2-year Stratum-specific Local Relapse Rate	Up to 2 years from registration	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).
2-year Overall Local Relapse Rate	Up to 2 years from registration	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).
2-year Disease-free Survival in All Patients	Up to 2 years from registration	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Adjuvant Chemotherapy + Chemoradiotherapy 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.	79
Total	79

Arm

Count

Adjuvant Chemotherapy + Chemoradiotherapy

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.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	3
Overall Study	Not eligible/not analyzable	26
Overall Study	not protocol specified	1
Overall Study	Progression	3
Overall Study	Withdrawal by Subject	4

Baseline characteristics

Characteristic	Adjuvant Chemotherapy + Chemoradiotherapy
Age, Continuous	62 years
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants
Margin of Resection Microscopically positive (R1)	25 participants
Margin of Resection Negative (R0)	54 participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	4 Participants
Race (NIH/OMB) Black or African American	7 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants
Race (NIH/OMB) White	66 Participants
Sex: Female, Male Female	41 Participants
Sex: Female, Male Male	38 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	78 / 79
serious Total, serious adverse events	2 / 79

Outcome results

Primary

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.

Time frame: Up to 2 years from registration