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

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00634725
• Other study ID #: CDR0000589283
• Secondary ID: GERCOR-LAP-07-D0
• Status: Completed
• Phase: Phase 3
• First received: March 12, 2008
• Last updated: December 10, 2015
• Start date: February 2008
• Est. completion date: September 2014

Study information

• Verified date: November 2012
• Source: Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: ANSM - Agence Nationale de sécurité du médicament et des produits de santé (French Competent Authority, previously called AFSSAPS)
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known which regimen of chemotherapy with or without erlotinib and/or radiation therapy is most effective in treating pancreatic cancer.

PURPOSE: This randomized phase III trial is studying giving gemcitabine together with or without capecitabine and/or radiation therapy to see how well it works compared with giving gemcitabine together with or without erlotinib in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

Description:

OBJECTIVES:

Primary

• 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

• 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.

• To evaluate the response rate in the CT and chemoradiotherapy (CRT) arms.

• To evaluate tolerance to erlotinib hydrochloride as maintenance treatment after the end of CT or CRT.

• To study the predictive molecular factors (i.e., survivin, K-ras, EGFR, PTEN, or AKT) of survival.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 820
• Est. completion date: September 2014
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status 0-2

• Life expectancy = 12 weeks

• Polynuclear neutrophils = 1.5 x 10^9/L

• Platelets = 100 x 10^9/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

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy (including abdominal radiotherapy) or chemotherapy for any reason

• No prior anti-epidermal growth factor-receptor therapy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• capecitabine

• erlotinib hydrochloride

• gemcitabine hydrochloride

Other:
• laboratory biomarker analysis

Radiation:
• radiation therapy

Locations

Country	Name	City	State
France	Centre Radiotherapie Oncologie Moyenne Garonne	Agen
France	Centre Hospitalier d'Aix en Provence	Aix en Provence
France	Centre Paul Papin	Angers
France	Centre Hospitalier d'Auxerre	Auxerre
France	Polyclinique Sainte Marguerite	Auxerre
France	Hopital Duffaut	Avignon
France	Institut Sainte Catherine	Avignon
France	Centre Hospitalier de la Cote Basque	Bayonne
France	Centre Hospitalier de Beauvais	Beauvais
France	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon
France	Hopital de Beziers	Beziers
France	Clinique Tivoli	Bordeaux
France	Hopital Saint Andre	Bordeaux
France	Institut Bergonie	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Hopital Ambroise Pare	Boulogne-Billancourt
France	Centre Hospitalier Pierre Oudot	Bourgoin-Jallieu
France	CHU de Caen	Caen
France	Polyclinique Du Parc	Caen
France	Hopital Beaujon	Clichy
France	Hopital Louis Pasteur	Colmar
France	Centre Hospitalier Compiegne	Compiegne
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
France	Centre Hospitalier de Dax	Dax
France	Centre Hospitalier de Digne les Bains	Digne Cedex
France	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon
France	Hopital Du Bocage	Dijon
France	Centre Hospitalier Draguignan	Draguignan
France	CHU de Grenoble - Hopital de la Tronche	Grenoble
France	Centre Hospitalier Departemental	La Roche Sur Yon
France	Centre Hospitalier de Lagny	Lagny Sur Marne
France	Hopital Louis Pasteur - Le Coudray	Le Coudray
France	Centre Hospitalier Universitaire de Bicetre	Le Kremlin Bicetre
France	Clinique Victor Hugo	Le Mans
France	Hopital Robert Boulin	Libourne
France	Polyclinique Du Bois	Lille
France	Polyclinique des Quatre Pavillons	Lormont
France	Centre Hospitalier St. Joseph St. Luc	Lyon
France	Centre Leon Berard	Lyon
France	Hopital de la Croix Rousse	Lyon
France	Hopital Edouard Herriot - Lyon	Lyon
France	Hopital Prive Jean Mermoz	Lyon
France	Centre Hospitalier Chanaux	Macon
France	CHU de la Timone	Marseille
France	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	Marseille
France	Centre Gray	Maubeuge
France	Centre Hospitalier de Meaux	Meaux
France	Centre Hospitalier General de Mont de Marsan	Mont-de-Marsan
France	Centre Hospitalier de Montelimar	Montelimar
France	C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau	Nimes
France	Clinique De Valdegour	Nimes
France	CHR D'Orleans - Hopital de la Source	Orleans
France	Hopital Bichat - Claude Bernard	Paris
France	Hopital Europeen Georges Pompidou	Paris
France	Hopital Pitie-Salpetriere	Paris
France	Hopital Saint Antoine	Paris
France	Hopital Saint Joseph	Paris
France	Hopital Saint-Louis	Paris
France	Hopital Tenon	Paris
France	Centre Catalan d'Oncologie	Perpignan
France	Hopital Haut Leveque	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHU Poitiers	Poitiers
France	Hopital Rene Dubos	Pontoise
France	CHU - Robert Debre	Reims
France	Hopital Charles Nicolle	Rouen
France	Centre Hospitalier	Saint-Omer
France	Centre Hospitalier de Tarbes	Tarbes
France	Centre Hospitalier Regional Metz Thionville	Thionville
France	CHRU de Tours - Hopital Trousseau	Tours
France	Nouvelle Clinique Generale	Valence
France	Centre Hospitalier Bretagne Atlantique	Vannes

Sponsors (1)

Lead Sponsor	Collaborator
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	an interim analysis is planned when 196 deaths will be observed	from the date of the first randomization to the date of patient death,due to any cause, or to the last date the patient was known to be alive, assessed up to 8 years after the beginning of the study	No
Secondary	Progression-free survival		time from the date of the first randomization to the date of progressive disease or death, assessed up to 8 years after the beginning of the study.	No
Secondary	Relationship between biological markers and survival	1 biopsy/patient of the pancreas before treatment	From baseline to death, assessed up to 8 years after the beginning of the study	No
Secondary	tolerance to erlotinib	To evaluate tolerance to erlotinib as maintenance treatment after the end of CT or CRT.; During each visit, any adverse events will be noted and graded according to version 3 of the NCI-CTCAE. Any adverse events that persist at the end of the CTI will be followed up until they disappear.	from start of treatment until the event has resolved or stabilized or until death	No