Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Gemcitabine With or Without Capecitabine and/or Radiation Therapy or Gemcitabine With or Without Erlotinib in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed by Surgery

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Biomarker/Laboratory analysis, Treatment	Active	18 and over	Other, Pharmaceutical / Industry	GERCOR-LAP-07-D07-1 GERCOR-LAP-07-D07-1, EU=20827, ROCHE-GERCOR-LAP-07-D07-1, EudraCT- 2007-001174-81, NCT00634725

Objectives

Primary

1. To assess whether administrating chemoradiotherapy in patients whose tumor is controlled after 4 months of induction chemotherapy (CT) increases survival compared with continuation of the same CT in patients with unresectable, locally advanced adenocarcinoma of the pancreas.

Secondary

1. To assess whether erlotinib hydrochloride combined with gemcitabine hydrochloride and administered as maintenance treatment increases progression-free survival compared with gemcitabine hydrochloride alone and without maintenance treatment.
2. To evaluate the response rate in the CT and chemoradiotherapy (CRT) arms.
3. To evaluate tolerance to erlotinib hydrochloride as maintenance treatment after the end of CT or CRT.
4. To study the predictive molecular factors (i.e., survivin, K-ras, EGFR, PTEN, or AKT) of survival.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the pancreas meeting the following criteria:
  • De novo locally advanced disease
  • Unresectable disease
  • Stage III according to the UICC classification
    • No distant metastases
    • No localized stage IA-IIB or metastatic stage IV disease according to UICC classification
  • Not considered for curative resection after pluridisciplinary discussion

Prior/Concurrent Therapy:

• No prior radiotherapy (including abdominal radiotherapy) or chemotherapy for any reason
• No prior anti-epidermal growth factor-receptor therapy

Patient Characteristics:

Inclusion criteria:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Polynuclear neutrophils ≥ 1.5 x 10⁹/L
• Platelets ≥ 100 x 10⁹/L
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • For patients who have had a recent biliary drain and whose bilirubin is descending, a value of ≤ 3 times ULN is acceptable
• Creatinine ≤ 2 mg/dL
• AST and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 5 times ULN
• Albumin ≥ 25 g/L
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of therapy

Exclusion criteria:

• Diarrhea ≥ grade 2 and/or uncontrolled diarrhea
• Affiliated with a social security regime
• Unable to follow instructions for psychological, familial, or geographical reasons
• Allergic to one of the ingredients in erlotinib hydrochloride
• Cancer within the past 5 years, except for in situ cancer of the neck of the uterus or basal cell skin cancer
• Severe infection
• Ophthalmic disease (i.e., inflammation, keratopathy, or infection)
• Symptomatic coronary or cardiac insufficiency, myocardial infarction, or stroke within the last 6 months
• Unable to take oral treatments
• Gastrointestinal disorders that could be associated with absorption disorders
• Untreated gastric or duodenal ulcer

Expected Enrollment

Outcomes

Overall survival
Comparisons on survival

Progression-free survival
Relationship between biological markers and resistance to treatment

Outline

This is a multicenter study. Patients in the first randomization are stratified according to center and ECOG performance status (0-1 vs 2). Patients in the second randomization are stratified according to center and initial treatment arm (I vs II).

• First randomization: Patients are randomized to 1 of 2 treatment arms.
  • Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43. Following the first evaluation, patients continue to receive gemcitabine hydrochloride on days 57, 64, 71, 85, 92, and 99 for a total of 4 months.
  
  
  
  • Arm II: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43. Following the first evaluation, patients continue to receive gemcitabine hydrochloride on days 57, 64, 71, 85, 92, and 99. Patients also receive oral erlotinib hydrochloride once daily for 4 months.
  
  
  

  After completion of treatment in the first randomization proceed to the second randomization.




• Second randomization: Patients are randomized to 1 of 4 treatment arms.
  • Arm I: Patients continue gemcitabine hydrochloride as in arm I in the first randomization on days 113, 120, and 127 and on days 141, 148, and 155 for 2 months in the absence of disease progression.
  
  
  
  • Arm II: Patients continue gemcitabine hydrochloride as in arm II in the first randomization on days 113, 120, and 127 and on days 141, 148, and 155 and oral erlotinib hydrochloride daily for 2 months followed by erlotinib hydrochloride alone as maintenance therapy in the absence of disease progression.
  
  
  
  • Arm III: Patients receive oral capecitabine twice daily and undergo radiotherapy beginning on day 127, 5 days a week, for 6 weeks, in the absence of disease progression.
  
  
  
  • Arm IV: Patients receive oral capecitabine twice daily and undergo radiotherapy beginning on day 127, 5 days a week, for 6 weeks. Beginning 15 days after completion of CRT, patients receive a reintroduction of oral erlotinib hydrochloride alone once daily in the absence of disease progression or unacceptable toxicity.
  
  
  

Tumor tissue will be analyzed for the relationship between biological markers and resistance to treatment.

After completion of study treatment, patients are followed every 2 months.

Trial Contact Information

Trial Lead Organizations

GERCOR Groupe Cooperateur Multidisciplinaire en Oncologie

P. Hammel, MD, PhD, Principal investigator		Ph: 33-14-087-5653 Email: pascal.hammel@bju.ap-hop-paris.fr

France
	Angers
	Centre Paul Papin
		Contact Person	Ph:  33-2-4135-3407
	Avignon
	Hopital Duffaut
		Contact Person	Ph:  33-4-3275-3121
	Institut Sainte Catherine
		Contact Person	Ph:  33-4-9027-6283
	Beauvais
	Centre Hospitalier
		Contact Person	Ph:  33-3-4411-2309
	Besancon
	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
		Contact Person	Ph:  33-3-8166-8393
	Bordeaux
	Clinique Tivoli
		Contact Person	Ph:  33-5-5611-0246
	Institut Bergonie
		Contact Person	Ph:  33-5-563-3333
	Polyclinique Bordeaux Nord Aquitaine
		Contact Person	Ph:  33-5-2630-7111
	Boulogne-Billancourt
	Hopital Ambroise Pare
		Contact Person	Ph:  33-1-4909-5873
	Bourgoin-Jallieu
	Centre Hospitalier Pierre Oudot
		Contact Person	Ph:  33-5-6251-5350
	Caen
	CHU de Caen
		Contact Person	Ph:  33-2-3145-5016
	Clermont-Ferrand
	Centre Jean Perrin
		Contact Person	Ph:  33-4-7327-8131
	Clichy
	Hopital Beaujon
		Contact Person	Ph:  33-140-875-653
			Email: pascal.hammel@bjn.aphp.fr
	Colmar
	Hopital Louis Pasteur
		Contact Person	Ph:  33-3-8912-4097
	Compiegne
	Centre Hospitalier Compiegne
		Contact Person	Ph:  33-3-4423-6278
	Creteil
	Centre Hospitalier Universitaire Henri Mondor
		Contact Person	Ph:  33-1-4981-2579
	Digne Cedex
	Centre Hospitalier de Digne les Bains
		Contact Person	Ph:  33-4-9230-1515
	Grenoble
	CHU de Grenoble - Hopital de la Tronche
		Contact Person	Ph:  33-4-7676-5451
	La Rochelle
	Hopital Saint - Louis
		Contact Person	Ph:  33-5-4645-8867
	Le Coudray
	Hopital Louis Pasteur - Le Coudray
		Contact Person	Ph:  33-2-3730-3030
	Le Kremlin Bicetre
	Centre Hospitalier Universitaire de Bicetre
		Contact Person	Ph:  33-1-4521-3722
	Le Mans
	Clinique Victor Hugo
		Contact Person	Ph:  33-2-4347-9494
	Lille
	Polyclinique Du Bois
		Contact Person	Ph:  33-3-2000-9757
	Lyon
	Centre Leon Berard
		Contact Person	Ph:  33-4-7878-2733
	Clinique Saint Jean
		Contact Person	Ph:  33-4-7878-1051
	Marseille
	CHU de la Timone
		Contact Person	Ph:  33-4-9138-6023
	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
		Contact Person	Ph:  33-4-9122-3302
	Nimes
	Clinique De Valdegour
		Contact Person	Ph:  33-4-6654-2110
	Paris
	Hopital Bichat - Claude Bernard
		Contact Person	Ph:  33-1-4025-7502
	Hopital Europeen Georges Pompidou
		Contact Person	Ph:  33-1-5609-3556
	Hopital Pitie-Salpetriere
		Contact Person	Ph:  33-1-4216-1045
	Hopital Saint Antoine
		Contact Person	Ph:  33-1-4928-2345
	Hopital Saint Joseph
		Contact Person	Ph:  33-1-4412-3078
	Hopital Tenon
		Contact Person	Ph:  33-1-5601-8322
	Perpignan
	Centre Catalan d'Oncologie
		Contact Person	Ph:  33-4-68-55-7496
	Pierre Benite
	Centre Hospitalier Lyon Sud
		Contact Person	Ph:  33-4-7886-4253
	Poitiers
	CHU Poitiers
		Contact Person	Ph:  33-5-4944-5425
	Reims
	CHU - Robert Debre
		Contact Person	Ph:  33-3-2678-8441
	Rouen
	Hopital Charles Nicolle
		Contact Person	Ph:  33-2-3288-8610
	Sainte-Etienne
	CHU Sainte-Etienne - Hopital Nord
		Contact Person	Ph:  33-4-9196-8737
	Tarbes
	Centre Hospitalier de Tarbes
		Contact Person	Ph:  33-5-6251-5350
	Thionville
	Centre Hospitalier Regional Metz Thionville
		Contact Person	Ph:  33-3-8755-3554
	Tours
	CHRU de Tours - Hopital Trousseau
		Contact Person	Ph:  33-2-4747-5900
	Valence
	Nouvelle Clinique Generale
		Contact Person	Ph:  33-4-7578-2466
	Vannes
	Centre Hospitalier Bretagne Atlantique
		Contact Person	Ph:  33-2-9701-4134

Registry Information
Official Title		Randomized Multicenter Phase III Study in Patients With Locally Advanced Adenocarcinoma of the Pancreas: Gemcitabine With or Without Chemoradiotherapy and With or Without Erlotinib. Intergroup Study
Trial Start Date		2008-02-07
Trial Completion Date		2011-05-07 (estimated)
Registered in ClinicalTrials.gov		NCT00634725
Date Submitted to PDQ		2008-03-06
Information Last Verified		2008-12-28