Clinical trial NCT00030732: Gemcitabine With or Without Capecitabine in Treating Patients With Advanced Pancreatic Cancer
Official title: Gemcitabine Plus Capecitabine Versus Gemcitabine Alone In Advanced Pancreatic Cancer. A Randomized Phase III Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: stage III pancreatic cancer
recurrent pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
Collaborators: name: Central European Cooperative Oncology Group
First posted: 2003-01-27
Enrollment: 319
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
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 determine the effectiveness of gemcitabine with or without capecitabine in treating patients who have advanced pancreatic cancer.

Detailed description: OBJECTIVES:

* Compare the overall survival of patients with advanced pancreatic cancer treated with gemcitabine with or without capecitabine.
* Compare the clinical benefit response, objective tumor response, duration of response, and time to progression in 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 a randomized, multicenter study. Patients are stratified according to metastases (yes vs no), pain (yes vs no), Karnofsky performance status (60-80% vs 90-100%), and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients initially receive gemcitabine IV over 30 minutes weekly for 7 weeks. After 1 week of rest, patients receive gemcitabine IV over 30 minutes weekly for 3 weeks. Treatment then repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, weekly for weeks 2-7, and then before each gemcitabine administration.

Patients are followed every 9 weeks.

PROJECTED ACCRUAL: A total of 300 patients (150 per treatment arm) will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed primary inoperable or metastatic pancreatic adenocarcinoma
* No CNS metastases

PATIENT CHARACTERISTICS:

Age:

* Over 18

Performance status:

* Karnofsky 60-100%

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 3,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 10.0 g/dL

Hepatic:

* Bilirubin no greater than 5 times normal
* AST/ALT no greater than 5 times normal
* Alkaline phosphatase no greater than 5 times normal

Renal:

* Creatinine clearance at least 30 mL/min

Gastrointestinal:

* No grade 2 or greater nausea or grade 1 or greater vomiting
* No medical condition that would interfere with taking oral medications or with gastrointestinal absorption (e.g., small bowel obstruction)

Other:

* No prior unanticipated severe reaction to fluoropyrimidine therapy
* No known hypersensitivity to fluorouracil
* No known dihydropyrimidine dehydrogenase deficiency
* No active infection
* No other serious concurrent systemic disorders that would preclude study participation
* No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell skin cancer
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior capecitabine
* No prior chemotherapy for advanced pancreatic cancer
* At least 1 year since prior radiochemotherapy for pancreatic cancer

Endocrine therapy:

* Not specified

Radiotherapy:

* See Chemotherapy
* At least 1 year since prior adjuvant radiotherapy for pancreatic cancer
* No concurrent radiotherapy

Surgery:

* Prior Whipple procedure or duodenal bypass allowed

Other:

* At least 1 month since prior investigational agents
* No concurrent sorivudine or its chemically related analogues (e.g., brivudine)
* No other concurrent anticancer or investigational drugs

Primary outcomes:
measure: Gemcitabine + Capecitabine vs. Gemcitabine alone
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Milan
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Naples
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Basel
country: Switzerland
facility: Saint Claraspital AG
city: Basel
country: Switzerland
facility: Universitatsspital-Basel
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Biel
country: Switzerland
facility: Spitalzentrum Biel
city: Chur
country: Switzerland
facility: Ratisches Kantons und Regionalspital
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Sion
country: Switzerland
facility: Institut Central des Hopitaux Valaisans
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Regionalspital
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: Oncology Institute of Southern Switzerland
city: Zurich
country: Switzerland
facility: UniversitaetsSpital
Study officials:
affiliation: Universitaetsspital-Basel
name: Richard Herrmann, MD
role: STUDY_CHAIR
affiliation: Allgemeines Krankenhaus - Universitatskliniken
name: Werner Scheithauer, MD
role: STUDY_CHAIR
References:
citation: Bernhard J, Dietrich D, Glimelius B, Hess V, Bodoky G, Scheithauer W, Herrmann R. Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy. Br J Cancer. 2010 Oct 26;103(9):1318-24. doi: 10.1038/sj.bjc.6605929. Epub 2010 Sep 28.
citation: Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schuller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Kohne CH, Mingrone W, Stemmer SM, Tamas K, Kornek GV, Koeberle D, Herrmann R; Central European Cooperative Oncology Group. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol. 2008 Aug 1;26(22):3695-701. doi: 10.1200/JCO.2007.15.6240.
citation: Hess V, Glimelius B, Grawe P, Dietrich D, Bodoky G, Ruhstaller T, Bajetta E, Saletti P, Figer A, Scheithauer W, Herrmann R. CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial. Lancet Oncol. 2008 Feb;9(2):132-8. doi: 10.1016/S1470-2045(08)70001-9.
citation: Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schuller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Kohne CH, Mingrone W, Stemmer SM, Tamas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W; Swiss Group for Clinical Cancer Research; Central European Cooperative Oncology Group. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol. 2007 Jun 1;25(16):2212-7. doi: 10.1200/JCO.2006.09.0886.
citation: Gargiulo P, Dietrich D, Herrmann R, Bodoky G, Ruhstaller T, Scheithauer W, Glimelius B, Berardi S, Pignata S, Brauchli P. Predicting mortality and adverse events in patients with advanced pancreatic cancer treated with palliative gemcitabine-based chemotherapy in a multicentre phase III randomized clinical trial: the APC-SAKK risk scores. Ther Adv Med Oncol. 2019 Jan 2;11:1758835918818351. doi: 10.1177/1758835918818351. eCollection 2019.