Clinical trial NCT00064207: Gemcitabine and Radiation Therapy Compared With Gemcitabine Alone in Treating Patients Who Have Undergone Surgery for Pancreatic Cancer
Official title: Randomized Phase II/III Study Comparing Gemcitabine Followed by Gemcitabine Plus Concomitant Radiation (50.4 Gy) Versus Control After Curative Pancreaticoduodenectomy for Pancreatic Head Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
stage I pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Federation Francophone de Cancerologie Digestive
First posted: 2003-07-09
Enrollment: 97
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 such as gemcitabine use different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving these treatments after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving gemcitabine together with radiation therapy is more effective than gemcitabine alone following surgery in treating pancreatic cancer.

PURPOSE: This randomized phase II/III trial is studying how well giving gemcitabine together with radiation therapy works and compares it to gemcitabine alone in treating patients who have undergone surgery for pancreatic cancer.

Detailed description: OBJECTIVES:

Phase II:

* Determine the feasibility of gemcitabine followed by chemoradiotherapy with gemcitabine vs gemcitabine alone after prior curative resection in patients with pancreatic head adenocarcinoma.
* Compare the tolerability of these regimens, in terms of acute and late toxicity, in these patients.

Phase III:

* Compare the disease-free and overall survival of patients treated with these regimens .
* Compare the quality of life of patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.
* Determine the sites of recurrence in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG/WHO performance status (0-1 vs 2), participating center, and N stage (N0 vs N1 vs NX). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Within 8 weeks after prior surgical resection, patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for 2 courses.

Patients then receive additional gemcitabine IV over 30 minutes on days 57, 64, 71, 78, 85, and 92. Beginning on day 57, patients also undergo radiotherapy once daily, 5 days a week, for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

* Arm II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for 4 courses.

Quality of life (QOL) is assessed in both arms, according to the following schedules:

* Arm I: QOL is assessed at baseline; at 3 weeks after the beginning of chemoradiotherapy; after the completion of chemoradiotherapy; every 3 months for 2 years; and then every 6 months for 1 year.
* Arm II: QOL is assessed at baseline; at 12 weeks; at 16 weeks; every 3 months for 2 years; and then every 6 months for 1 year.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 538 patients (269 per treatment arm) will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed pancreatic head adenocarcinoma
* Prior pancreaticoduodenectomy required

  * Documented histological examination of surgical margins (R0), including retroperitoneal margin
  * Performed within the past 8 weeks
* Any number of lymph nodes (less than 10 OR 10 or more) allowed
* No periampullary cancer

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2 OR
* WHO 0-2

Life expectancy

* Not specified

Hematopoietic

* WBC greater than 3,500/mm\^3
* Platelet count greater than 150,000/mm\^3
* Hemoglobin greater than 9.0 g/dL

Hepatic

* Bilirubin less than 1.5 times normal
* AST and ALT less than 3.0 times normal

Renal

* Creatinine less than 1.2 mg/dL

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
* No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy

Chemotherapy

* No prior chemotherapy
* No other concurrent chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy

Surgery

* See Disease Characteristics
* Recovered from prior surgery

Other

* No other concurrent anticancer agents

Primary outcomes:
measure: Feasibility of full completion of treatment as measured by the number of patients completing treatment 1 month after treatment in phase II
measure: Tolerability in terms of acute toxicity as measured by NCI-CTC v2.0 1 month after completion of treatment in phase II
measure: Tolerability in terms of late toxicity as measured by EORTC and RTOG 1 month after completion of treatment in phase II
measure: Overall survival as measured by Logrank every 3 months in years 1-2, and every 6 months thereafter in phase III
Secondary outcomes:
measure: Disease-free survival as measured by Logrank every 3 months in years 1-2, and every 6 months thereafter
measure: Acute toxicity as measured by NCI-CTC v2.0 every 3 months in years 1-2, and every 6 months thereafter
measure: Late toxicity as measured by EORTC and RTOG every 3 months in years1-2, and every 6 months thereafter
measure: Quality of life as measured by Quality of Life Questionnaire Core 30 (QLQ-C30) v3.0 and EORTC QLQ PAN-26 every 3 months in years 1-2 and every 6 months thereafter
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Haine Saint Paul
country: Belgium
facility: Hopital de Jolimont
city: Kortrijk
country: Belgium
facility: Cazk Groeninghe - Campus St-Niklaas
city: Liege
country: Belgium
facility: CHU Liege - Domaine Universitaire du Sart Tilman
city: Wilrijk
country: Belgium
facility: Algemeen Ziekenhuis Sint-Augustinus
city: Abbeville
country: France
facility: Centre Hospitalier d'Abbeville
city: Annecy
country: France
facility: Centre Hospitalier d'Annecy
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Avignon
country: France
facility: Hopital Duffaut
city: Beauvais
country: France
facility: C.H.G. Beauvais
city: Blois
country: France
facility: Centre Hospitalier de Blois
city: Bordeaux
country: France
facility: Clinique Tivoli
city: Boucher
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Boulogne Billancourt
country: France
facility: Centre Hospitalier Universitaire Ambroise Pare - Boulogne
city: Boulogne Sur Mer
country: France
facility: Centre Hospitalier Docteur Duchenne
city: Bourgoin-Jallieu
country: France
facility: Centre Hospitalier Pierre Oudot
city: Caen
country: France
facility: CHU de Caen
city: Clermont-Ferrand
country: France
facility: CHR Clermont Ferrand, Hotel dieu
city: Clichy
country: France
facility: Hopital Beaujon
city: Colombes Cedex
country: France
facility: Louis Mourier Hospital
city: Creteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Dax
country: France
facility: Centre Hospitalier de Dax
city: Dijon
country: France
facility: Hopital Du Bocage
city: Elbeuf
country: France
facility: Centre Hospitalier Intercommunal St. Aubin les Elbeuf
city: Grenoble
country: France
facility: CHU de Grenoble - Hopital de la Tronche
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Libourne
country: France
facility: Hopital Robert Boulin
city: Limoges
country: France
facility: Centre Hospital Regional Universitaire de Limoges
city: Lyon
country: France
facility: Clinique Saint Jean
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: CHU de la Timone
city: Mont-de-Marsan
country: France
facility: Centre Hospitalier General de Mont de Marsan
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Mulhouse
country: France
facility: Centre Hospitalier de Mulhouse
city: Nimes
country: France
facility: C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: CHU Pitie-Salpetriere
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Tenon
city: Pau
country: France
facility: C.H.G. De Pau
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU Poitiers
city: Rouen
country: France
facility: Hopital Charles Nicolle
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: Hopital Universitaire Hautepierre
city: Tours
country: France
facility: Centre Hospitalier Universitaire Bretonneau de Tours
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Berlin
country: Germany
facility: Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Mainz
country: Germany
facility: Johannes Gutenberg University
city: Munich
country: Germany
facility: Munich Oncologic Practice at Elisenhof
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
Study officials:
affiliation: Erasme University Hospital
name: Jean-Luc Van Laethem, MD, PhD
role: STUDY_CHAIR
affiliation: Charite University, Berlin, Germany
name: Volker G. Budach, MD, PhD
role: STUDY_CHAIR
affiliation: Hopital Beaujon
name: Pascal Hammel, MD, PhD
role: STUDY_CHAIR
References:
citation: Van Laethem JL, Hammel P, Mornex F, Azria D, Van Tienhoven G, Vergauwe P, Peeters M, Polus M, Praet M, Mauer M, Collette L, Budach V, Lutz M, Van Cutsem E, Haustermans K. Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study. J Clin Oncol. 2010 Oct 10;28(29):4450-6. doi: 10.1200/JCO.2010.30.3446. Epub 2010 Sep 13.
citation: Van Laethem J, Van Cutsem E, Hammel P, et al.: Adjuvant chemotherapy alone versus chemoradiation after curative resection for pancreatic cancer : feasibility results of a randomised EORTC/FFCD/GERCOR phase II/III study (40013/22012/0304). [Abstract] J Clin Oncol 26 (Suppl 15): A-4514, 2008.