AdBTC-1: Adjuvant Chemotherapy for Biliary Tract Cancer After Curative Resection

Sponsor

Tianjin Medical University Cancer Institute and Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03779035

Collaborator

(none)

460

Enrollment

Location

Arms

60.5

Anticipated Duration (Months)

7.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This prospective, open-Label, comparative, randomized, controlled phase III trial was designed to compare the clinical performance of gemcitabine with capecitabine vs. capecitabine alone for patients with biliary tract cancer (BTC) after curative resection.

Condition or Disease	Intervention/Treatment	Phase
Cholangiocarcinoma Gall Bladder Carcinoma	Drug: Gemcitabine Drug: Capecitabine	Phase 3

Detailed Description

Currently, complete surgical resection represents the only potentially curative treatment option for cholangiocarcinoma (CCA, including intrahepatic, hilar and distal CCA) and gallbladder carcinoma (GBCA). Because of high rates of disease recurrence and poor survival rates following surgical resection, postoperative treatment have been considered to improve patient survival after resection of BTC. The systematic review showed a beneficial impact of adjuvant treatment in BTC, particularly in patients with involved lymph nodes or resection margins and distal or hilar CCA. However, in regard of the paucity of randomized data, current guidelines recommend inclusion in clinical trials.

Previously, the data of the BILCAP trial showed an improvement in median overall survival for capecitabine compared to observation alone for BTC, indicating capecitabine as the new standard postoperative treatment after curative resection of BTC.

Previous phase II studies for advanced BTC showed superiority of the combination gemcitabine/ capecitabine regimen vs. the capecitabine monotherapy, the median OS was 12.7-14 vs. 7.9 months.

Based on these data, this AdBTC trial will was designed to compare the clinical performance of gemcitabine with capecitabine vs. capecitabine alone for patients with biliary tract cancer (BTC) after curative resection, aiming for superiority of the combination regimen vs. the oral monotherapy. This will be based on the BILCAP protocol, applying the similar dosing, assessments and dose modifications.

The primary endpoint is DFS and secondary endpoints include recurrence free survival, OS, safety and tolerability of adjuvant CTx, quality of life, and patterns of disease recurrence.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

460 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Adjuvant Chemotherapy With Gemcitabine and Capecitabine Compared to Capecitabine for Biliary Tract Cancer After Curative Resection

Anticipated Study Start Date :

Dec 15, 2018

Anticipated Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine plus Capecitabine Gemcitabine (1000 mg per square meter) on days 1 and 8 Capecitabine (1250 mg per square meter) twice a day on days 1-14. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.	Drug: Gemcitabine 1000mg/m2 Drug: Capecitabine 1250mg/m2
Active Comparator: Capecitabine Capecitabine (1250 mg per square meter) twice a day on days 1-14. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.	Drug: Capecitabine 1250mg/m2

Arm

Intervention/Treatment

Experimental: Gemcitabine plus Capecitabine

Gemcitabine (1000 mg per square meter) on days 1 and 8 Capecitabine (1250 mg per square meter) twice a day on days 1-14. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.

Drug: Gemcitabine

1000mg/m2

Drug: Capecitabine

1250mg/m2

Active Comparator: Capecitabine

Capecitabine (1250 mg per square meter) twice a day on days 1-14. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.

Drug: Capecitabine

1250mg/m2

Outcome Measures

Primary Outcome Measures

Disease free survival (DFS) rate [at 24 months]
DFS

Secondary Outcome Measures

Overall survival (OS) rate [at 24 months]
OS
Disease free survival (DFS) rate [at 60 months]
DFS
Overall survival (OS) rate [at 60 months]
OS
The rate of patients with hepatic or locoregional recurrence [24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed biliary tract cancer (including intrahepatic, extrahepatic, hilar cholangiocarcinoma or muscle invasive gallbladder cancer or cancer of the distal bile duct)
Must have undergone a radical surgical approach which includes liver resection, pancreatic resection, or less commonly both
Patients with pathological evidence of microscopic involvement of the margins of the excised specimen are eligible as long as resection is macroscopically complete
Must be able to start treatment within 12 weeks of surgery
No pancreatic or periampullary cancer
No mucosal gallbladder cancer

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Urea < 1.5 times upper limit of normal (ULN)
Creatinine < 1.5 times ULN
Glomerular filtration rate ≥ 60 mL/min (if < 60 mL/min, adequate renal function for capecitabine must be confirmed by isotope EDTA)
Hemoglobin ≥ 10 g/dL
WBC ≥ 3,000/mm³
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Bilirubin ≤ 3 times ULN
ALT and AST ≤ 5 times ULN
Adequate surgical biliary drainage with no evidence of infection
Not pregnant or nursing
Negative pregnancy test for women of childbearing age and childbearing potential
Fertile patients must use effective contraception during study treatment and for at least 3 months after study treatment has ended
Must provide written informed consent
No history of other malignant diseases within the past 5 years
No serious coexisting medical condition likely to interfere with protocol treatment, including a potential serious infection
No evidence of significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial
No psychological, familial, sociological, or geographical factors considered likely to preclude study compliance
No other serious uncontrolled medical conditions
No unresolved biliary tree obstruction

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Completely recovered from prior surgery
No use of other investigational agents within 28 days prior to and during study treatment
No prior chemotherapy or radiotherapy for biliary tract cancer
No other concurrent anticancer chemotherapy, radiotherapy, or investigational agent