Clinical trial NCT00032175: Gemcitabine With or Without Capecitabine in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
Official title: A Phase III Multicenter Randomized Clinical Trial Comparing Gemcitabine Alone Or In Combination With Capecitabine For The Treatment Of Patients With Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: stage III pancreatic cancer
duct cell adenocarcinoma of the pancreas
stage IV pancreatic cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 508
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if gemcitabine is more effective with or without capecitabine in treating pancreatic cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of gemcitabine with or without capecitabine in treating patients who have locally advanced or metastatic pancreatic cancer.

Detailed description: OBJECTIVES:

* Compare the 1-year survival rate of patients with locally advanced or metastatic pancreatic cancer treated with gemcitabine with or without capecitabine.
* Compare the median and 2-year survival rates and the objective response rates of patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.
* Compare the quality of life of patients treated with these regimens.

OUTLINE: This is an randomized, open-label, multicenter study. Patients are stratified according to disease stage (locally advanced vs metastatic) and performance status (0 and 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43 during the first course. After a 1-week rest period, patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15. Subsequent courses repeat every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 3 months for 1 year, and then annually thereafter.

Patients are followed every 3 months.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 508 patients (254 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed ductal adenocarcinoma of the pancreas

  * Locally advanced or metastatic disease not amenable to curative surgical resection
  * Macroscopic residual disease after prior resection with histological confirmation is allowed
* Unidimensionally measurable disease
* No intracerebral metastases or meningeal carcinomatosis

PATIENT CHARACTERISTICS:

Age:

* Over 18

Performance status:

* WHO 0-2

Life expectancy:

* More than 3 months

Hematopoietic:

* WBC greater than 3,000/mm3
* Neutrophil count greater than 1,500/mm3
* Platelet count greater than 100,000/mm3

Hepatic:

* Bilirubin less than 2 mg/dL

Renal:

* Creatinine less than 2 mg/dL
* Creatinine clearance greater than 50 mL/min

Cardiovascular:

* No New York Heart Association class III or IV heart disease
* No uncontrolled angina pectoris

Other:

* No other prior malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
* No other concurrent uncontrolled medical condition
* No other medical or psychiatric condition that would preclude study
* No known hypersensitivity to fluorouracil
* No dihydropyrimidine dehydrogenase deficiency
* No known malabsorption syndromes
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy (including preoperative or adjuvant) for this disease
* No other concurrent cytotoxic chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy (including preoperative or adjuvant) for this disease

Surgery:

* See Disease Characteristics

Other:

* No prior investigational drugs (including preoperative or adjuvant) for this disease
* No other concurrent investigational drugs
* No concurrent dipyridamole or allopurinol
* No concurrent sorivudine or sorivudine analogs (e.g., brivudine) (capecitabine arm only)

Primary outcomes:
measure: Survival at 1 year
Secondary outcomes:
measure: Quality of life
measure: Median survival rate
measure: Survival rate at 2 years
measure: Toxicity
measure: Objective response rate
Other outcomes:
Locations:
city: Bath
country: United Kingdom
facility: Royal United Hospital
state: England
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital NHS Trust
state: England
city: King's Lynn
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Leeds
country: United Kingdom
facility: Cookridge Hospital at Leeds Teaching Hospital NHS Trust
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Cancer Research UK Liverpool Cancer Trials Unit
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: England
city: London
country: United Kingdom
facility: St. Thomas' Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Trust
state: England
city: Middlesbrough, Cleveland
country: United Kingdom
facility: James Cook University Hospital at South Tees Hospitals NHS Trust
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Poole Dorset
country: United Kingdom
facility: Poole Hospital NHS Trust
state: England
city: Prescot Merseyside
country: United Kingdom
facility: Whiston Hospital
state: England
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
state: England
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
state: England
city: Southampton
country: United Kingdom
facility: Royal South Hants Hospital
state: England
city: Stoke-On-Trent
country: United Kingdom
facility: University Hospital of North Staffordshire
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
city: Warrington
country: United Kingdom
facility: Warrington Hospital NHS Trust
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Swansea
country: United Kingdom
facility: Singleton Hospital of the Swansea NHS Trust
state: Wales
Study officials:
affiliation: Cancer Research UK
name: Emily Owen
References:
citation: Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009 Nov 20;27(33):5513-8. doi: 10.1200/JCO.2009.24.2446. Epub 2009 Oct 26.