A Multicenter, Randomized Phase II Trial Assessing the Activity of Gemcitabine - Oxaliplatin Chemotherapy Alone or in Combination With Cetuximab in Patients With Advanced Biliary Cancer.
1. Adenocarcinoma of the biliary tract (gallbladder, intra and/or extrahepatic bile
ducts, or ampulla of Vater):
- Cytologically or histologically confirmed. In case of uncertain biliary tract
origin (e.g., intrahepatic, peripheral cholangiocarcinomas), inclusion is
possible if i) extensive search for primary (thoracic and abdominopelvic CT
scan, colonoscopy, upper digestive endoscopy, serum PSA level for men or
mammography for women, and FDG-PET if possible) is negative; and ii)
histological examination is consistent with bile duct adenocarcinoma (IHC should
ideally be performed and be consistent with biliary primary, e.g., positive for
cytokeratin 7 and 19 and negative for cytokeratin 20).
- not amenable to curative resection, or recurrent after resection (i.e., locally
advanced or metastatic),
- With at least one unidimensionally measurable target lesion in a non-irradiated,
non-PDT-treated area (longest diameter 1 cm [spiral CT scan]), or 2 cm
[conventional CT scan]).
- With biliary obstruction controlled,
2. Age between 18 and 75 years.
3. World Health Organization (WHO) performance status of 0 or 1.
4. Life expectancy higher than 3 months.
5. No prior chemotherapy for advanced disease. Previous adjuvant chemotherapy is allowed
(completed at least 6 months previously, if containing gemcitabine or platinum
salts). Previous irradiation (external radiotherapy, brachytherapy) and PDT are
allowed provided that there is at least one unidimensionally measurable target lesion
in untreated area.
6. Bilirubin 3 times the upper limit of the normal range (ULN). Pts with jaundice or
evidence of bile duct obstruction, in whom the biliary tree can be decompressed by
endoscopic or percutaneous endoprothesis with subsequent reduction in bilirubin £ 3
ULN, will be eligible for the study.
7. Aminotransferases (AST, ALT) 5 ULN, INR < 1.5 (following vitamin K1 injection in
patients with current or recent history of jaundice or bile duct obstruction),
creatinine 1.5 ULN, neutrophils 1.5 109/L, platelets 100 109/L, hemoglobin 9 g/dL
(red blood cell transfusion if needed is allowed).
8. Written informed consent. Note: EGFR tumor status has to be known for every pt, but
it is neither an inclusion/exclusion criterion nor a stratification factor. EGFR
expression has to be assessed by IHC using biopsy or surgical material, at any time
prior to inclusion into the study.
1. Known central nervous system metastases.
2. Contraindication or history of grade 3-4 allergy reaction to one treatment component.
3. Surgery (except diagnostic biopsy), external radiotherapy, brachytherapy, or PDT
within 30 days prior to start of treatment. Prior adjuvant chemotherapy is only
allowed if completed at least 30 days previously (6 months if containing gemcitabine
or platinum salts).
4. Participation in another clinical trial within 30 days prior to start of treatment.
5. Concomitant systemic chronic immunotherapy, chemotherapy, or antitumor hormone
6. Previous administration of EGFR inhibitors or EGF.
7. Active uncontrolled infection, peripheral neuropathy grade 2, acute or subacute
bowel obstruction or history of inflammatory bowel disease, symptomatic coronary
disease or myocardial infarction in the past 6 months, congestive heart failure (NYHA
class II), interstitial pneumonitis or respiratory failure, or renal failure.
8. Pregnancy (or positive b-HCG dosage at baseline), breast-feeding, or lack of
effective contraception in male or female pts of reproductive potential.
9. Other malignancies either currently active or in the last 5 years, except adequately
treated in situ carcinoma of the cervix and basal or squamous cell skin carcinoma.
10. Legal incapacity or physical, psychological or mental status interfering with the
pt's ability to terminate the study or to sign the informed consent.