Gemcitabine With or Without Cisplatin in Treating Patients With Unresectable Locally Advanced or Metastatic Cholangiocarcinoma or Other Biliary Tract Tumors

Gallbladder Cancer Clinical Trial

— ABC-02  

Official title:

Gemcitabine, Alone or in Combination With Cisplatin, in Patients With Advanced or Metastatic Cholangiocarcinomas and Other Biliary Tract Tumors: A Multicentre, Randomized Phase III Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00262769
• Other study ID #: CDR0000455013
• Secondary ID: CRUK-ABC-02EU-20
• Status: Completed
• Phase: Phase 3
• First received: December 6, 2005
• Last updated: July 16, 2012
• Start date: May 2005

Study information

• Verified date: July 2012
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health ServiceUnited Kingdom: National Institute for Health ResearchUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether gemcitabine is more effective with or without cisplatin in treating cholangiocarcinoma or biliary tract tumors.

PURPOSE: This randomized phase III trial is studying gemcitabine and cisplatin to see how well they work compared to gemcitabine alone in treating patients with unresectable locally advanced or metastatic cholangiocarcinoma or other biliary tract tumors.

Description:

OBJECTIVES:

Primary

• Compare the overall survival of patients with unresectable locally advanced or metastatic cholangiocarcinoma or other biliary tract tumors treated with gemcitabine hydrochloride with vs without cisplatin.

Secondary

• Compare the progression-free survival of patients treated with these regimens.

• Compare the toxic effects of these regimens in these patients.

• Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, primary site of disease (gallbladder vs bile ducts vs ampulla), prior therapy (photodynamic therapy [PDT] vs non-PDT therapy vs none), ECOG performance status (0 vs 1 vs 2), and disease status (locally advanced vs metastatic). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and

15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 1½ hours on days 1 and 8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 12 weeks, and after finishing treatment.

After completion of study treatment, patients are followed periodically for at least 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 324
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed biliary tract, gallbladder, or ampullary carcinoma

• Intra- or extra-hepatic disease allowed

• Unresectable locally advanced, recurrent, or metastatic disease

• No brain metastases

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 10 g/dL (transfusion allowed)

• WBC = 3,000/mm^3

Hepatic

• AST and ALT = 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)

• Bilirubin = 1.5 times ULN

• Alkaline phosphatase = 3 times ULN (5 times ULN if liver metastases are present)

• Adequate biliary drainage

• No unresolved biliary tract obstruction

Renal

• Creatinine < 1.5 times ULN

• Urea < 1.5 times ULN

• Glomerular filtration rate (GFR) = 45 mL/min

• If GFR < 60 mL/min, isotope EDTA confirmation of adequate renal function is required

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after study participation

• No active, uncontrolled infection

• No other severe or uncontrolled systemic disease

• No other malignancy within the past 5 years except nonmetastatic basal cell or squamous cell skin cancer or carcinoma in situ of the cervix treated by cone-biopsy or resection

• No psychiatric disorder that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

Chemotherapy

• At least 6 months since prior adjuvant chemotherapy

• No prior gemcitabine hydrochloride

• No prior cisplatin

• No prior systemic chemotherapy for locally advanced or metastatic disease except low-dose radiosensitizing chemotherapy in conjunction with radiotherapy

Radiotherapy

• Prior radiotherapy for localized disease allowed provided there is clear evidence of disease progression afterwards

Surgery

• Prior curative surgery allowed provided there is evidence of nonresectable disease relapse requiring systemic chemotherapy

Other

• Recovered from all prior therapies

• Prior photodynamic therapy (PDT) allowed provided it was given for localized disease only (with no evidence of metastatic disease) and resulted in subsequent disease progression after completion of therapy OR to relieve biliary obstruction in the presence of metastatic disease

• PDT must have been completed = 4 weeks ago

• At least 4 weeks since prior investigational agents

• No other concurrent, curative anticancer therapy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bile Duct Neoplasms
• Cholangiocarcinoma
• Extrahepatic Bile Duct Cancer
• Gallbladder Cancer
• Gallbladder Neoplasms

Intervention

Drug:
• cisplatin
25 mg/m2 in 1000 mls 0.9% saline given over 1 hour followed by 500 mls 0.9% saline over 90 mins
• gemcitabine hydrochloride
1000mg/m2 in 250-500mls 0.9% saline over 30 mins by intravenous infusions on day 1, 8 and 15 (Arm A only) of each 28 (Arm A) or 21 (Arm B) day cycle.

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England
United Kingdom	Belfast City Hospital Trust Incorporating Belvoir Park Hospital	Belfast	Northern Ireland
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Cumberland Infirmary	Carlisle	England
United Kingdom	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England
United Kingdom	Derbyshire Royal Infirmary	Derby	England
United Kingdom	Princess Alexandra Hospital	Essex	England
United Kingdom	Gloucestershire Royal Hospital	Gloucester	England
United Kingdom	Princess Royal Hospital at Hull and East Yorkshire NHS Trust	Hull	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Hammersmith Hospital	London	England
United Kingdom	Helen Rollason Cancer Care Centre at North Middlesex Hospital	London	England
United Kingdom	Royal Marsden - London	London	England
United Kingdom	UCL Cancer Institute	London	England
United Kingdom	University College of London Hospitals	London	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Nottingham City Hospital	Nottingham	England
United Kingdom	Portsmouth Oncology Centre at Saint Mary's Hospital	Portsmouth Hants	England
United Kingdom	Glan Clwyd Hospital	Rhyl, Denbighshire	Wales
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	Eli Lilly and Company

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	From date of randomisation till date of death or last date of follow-up (up to 5 years)	From date of randomisation till date of death or last date of follow-up (up to 5 years)	No
Secondary	Progression-free survival	From date of randomisation till date of death or last date of follow-up (up to 5 years)	From date of randomisation till date of death or last date of follow-up (up to 5 years)	No
Secondary	Quality of life	Quality of life as measured by EORTC Quality of Life Questionnaire Core 30 Items periodically	Before and 12 weeks after completion of treatment	No
Secondary	Toxicity	Toxicity as measured by NCI CTC periodically. The proportion of patients who experience a toxicity of grade 3 or 4 will be compared between the two arms of the trial.	During treatment and follow-up	Yes