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
18 Years
N/A
Both
Pancreatic Cancer
Trial Information
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
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.
Inclusion 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
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall survival
Outcome Description:
an interim analysis is planned when 196 deaths will be observed
Outcome Time Frame:
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
Safety Issue:
No
Principal Investigator
Pascal Hammel, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Hopital Beaujon
Authority:
France: ANSM - Agence Nationale de sécurité du médicament et des produits de santé (French Competent Authority, previously called AFSSAPS)
Study ID:
CDR0000589283
NCT ID:
NCT00634725
Start Date:
February 2008
Completion Date:
February 2016
Related Keywords:
- Pancreatic Cancer
- adenocarcinoma of the pancreas
- stage III pancreatic cancer
- Adenocarcinoma
- Pancreatic Neoplasms
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