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

Sponsor

University College, London (Other)

Overall Status

Completed

CT.gov ID

NCT00262769

Collaborator

Eli Lilly and Company (Industry)

324

Enrollment

Locations

Arms

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Extrahepatic Bile Duct Cancer Gallbladder Cancer	Drug: cisplatin Drug: gemcitabine hydrochloride	Phase 3

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

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 Design

Study Type:

Interventional

Actual Enrollment :

324 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

May 1, 2005

Actual Primary Completion Date :

Aug 1, 2008

Arms and Interventions

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: 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 cis-diamminedichloroplatinum(II) cisplatinum 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

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: 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

cis-diamminedichloroplatinum(II)

cisplatinum

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

Outcome Measures

Primary Outcome Measures

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

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 [Before and 12 weeks after completion of treatment]
Quality of life as measured by EORTC Quality of Life Questionnaire Core 30 Items periodically
Toxicity [During treatment and follow-up]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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