Gemcitabine With or Without Cisplatin in Treating Patients With Unresectable Locally Advanced or Metastatic Cholangiocarcinoma or Other Biliary Tract Tumors (ABC-02)

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

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.

Study Overview

• Status: Completed
• Conditions: Gallbladder Cancer; Extrahepatic Bile Duct Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: cisplatin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Basingstoke, England, United Kingdom, RG24 9NA
      • Basingstoke and North Hampshire NHS Foundation Trust
    • Birmingham, England, United Kingdom, B15 2TH
      • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital
    • Carlisle, England, United Kingdom, CA2 7HY
      • Cumberland Infirmary
    • Cheltenham, England, United Kingdom, GL53 7AN
      • Gloucestershire Oncology Centre at Cheltenham General Hospital
    • Derby, England, United Kingdom, DE1 2QY
      • Derbyshire Royal Infirmary
    • Essex, England, United Kingdom, CM20 1QX
      • Princess Alexandra Hospital
    • Gloucester, England, United Kingdom, GL1 3NN
      • Gloucestershire Royal Hospital
    • Hull, England, United Kingdom, HU8 9HE
      • Princess Royal Hospital at Hull and East Yorkshire NHS Trust
    • Leeds, England, United Kingdom, LS9 7TF
      • Leeds Cancer Centre at St. James's University Hospital
    • London, England, United Kingdom, SW3 6JJ
      • Royal Marsden - London
    • London, England, United Kingdom, W12 OHS
      • Hammersmith Hospital
    • London, England, United Kingdom, WIT 3AA
      • University College of London Hospitals
    • London, England, United Kingdom, N18 1QX
      • Helen Rollason Cancer Care Centre at North Middlesex Hospital
    • London, England, United Kingdom, WC1E 6DD
      • UCL Cancer Institute
    • Maidstone, England, United Kingdom, ME16 9QQ
      • Maidstone Hospital
    • Merseyside, England, United Kingdom, CH63 4JY
      • Clatterbridge Centre for Oncology
    • Northwood, England, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre at Mount Vernon Hospital
    • Nottingham, England, United Kingdom, NG5 1PB
      • Nottingham City Hospital
    • Portsmouth Hants, England, United Kingdom, PO3 6AD
      • Portsmouth Oncology Centre at Saint Mary's Hospital
    • Sheffield, England, United Kingdom, S10 2SJ
      • Cancer Research Centre at Weston Park Hospital
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 7AB
      • Belfast City Hospital Trust Incorporating Belvoir Park Hospital
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 2TL
      • Velindre Cancer Center at Velindre Hospital
    • Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
      • Glan Clwyd Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A - Gemcitabine; Gemcitabine alone	Drug: 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.; Other Names: Gemzar
Experimental: B - Gemcitabine and Cisplatin; Gemcitabine and Cisplatin	Drug: 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.; Other Names: Gemzar; 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; Other Names: CDDP; cisplatinum; cis-diamminedichloroplatinum(II)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Eli Lilly and Company
• Investigators: Study Chair: John A. Bridgewater, University College London (UCL) Cancer Institute

Publications and helpful links

General Publications

• 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. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: December 6, 2005
• First Submitted That Met QC Criteria: December 6, 2005
• First Posted (Estimate): December 7, 2005

Study Record Updates

• Last Update Posted (Estimate): July 17, 2012
• Last Update Submitted That Met QC Criteria: July 16, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: unresectable gallbladder cancer; recurrent gallbladder cancer; unresectable extrahepatic bile duct cancer; recurrent extrahepatic bile duct cancer; metastatic gallbladder cancer; cholangiocarcinoma of the gallbladder; metastatic extrahepatic bile duct cancer; cholangiocarcinoma of the extrahepatic bile duct
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Gallbladder Diseases; Biliary Tract Diseases; Bile Duct Diseases; Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms; Bile Duct Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Cisplatin
• Other Study ID Numbers: CDR0000455013; CRUK-ABC-02; EU-205103; ISRCTN82956140; EUDRACT-2004-004882-14; CTA-21266/0005/001