Gemcitabine, Oxaliplatin and Capecitabine for Advanced Pancreatic Carcinoma

Gemcitabine, Oxaliplatin and Capecitabine (GEMOXEL) for Patients With Advanced Pancreatic Adenocarcinoma (APC): A Phase I/II Study

Gemcitabine is the mainstay of palliative chemotherapy for patients with advanced pancreatic cancer (APC). Recent randomized trials have shown increased clinical benefit with the addition of oxaliplatin and prolonged median survival with the addition of capecitabine to gemcitabine. Gemcitabine, capecitabine and oxaliplatin are 3 newer, well tolerated anticancer drugs with mild and non-overlapping toxicity profiles. We therefore propose a dose-finding and safety study of the triple combination gemcitabine, capecitabine and oxaliplatin in patients with APC (Phase I part), followed by a phase II part to assess preliminary efficacy of this triple combination.

Primary Objectives:

• Phase I: to determine the maximum tolerated dose (MTD) of oxaliplatin in combination with gemcitabine and capecitabine (GEMOXEL) in patients with APC
• Phase II: to assess any anti-tumor activity of GEMOXEL in patients with APC

Secondary Objectives:

• to assess toxicity and safety of the combination treatment GEMOXEL in patients with APC

Primary Endpoints:

• Phase I: Dose-limiting toxicity
• Phase II: Objective tumor response

Secondary Endpoints:

• Toxicity at MTD according to NCI CTC 3.0
• Progression-free survival and Overall Survival

Inclusion Criteria:

• Cytologically or histologically confirmed adenocarcinoma of the exocrine pancreas
• Disease non-resectable and locally advanced or metastatic
• Measurable disease or evaluable disease i.e. tumor marker CA19-9 at baseline ≥ 1.5 x upper limit of normal (ULN)
• Age >18 years
• Karnofsky performance status ≥ 60%
• Life expectancy of at least 3 months
• Written informed consent
• Willing and able to comply with the protocol for the duration of the study

Exclusion Criteria:

• Prior chemotherapy for pancreatic cancer
• Prior adjuvant radio- or radiochemotherapy for pancreatic cancer within 12 months of inclusion
• Known CNS metastases at the time of enrollment
• Neutrophil count ≤ 1.5 x109/l, platelet count ≤100 x109/l, hemoglobin ≤ 10g/dl
• Serum creatinine > 1.25 x ULN
• ASAT, ALAT and alkaline phosphatase > 2.5 ULN or > 5 ULN in the presence of liver metastasis, Bilirubin > 1.5 ULN (after treatment of obstructive jaundice eg. stent)
• Pregnant or breast feeding women (women of childbearing potential must have a negative pregnancy test at baseline)
• Men and women of reproductive potential who are not using an effective method of contraception
• Clinically significant cardiac disease (NYHA III-IV) or myocardial infarction within the last 12 months
• Neurological disease with dys-/paraesthesias > grade 1 according to NCI CTC
• Any serious concomitant disorder incompatible with the trial (in the judgement of the investigator)
• Psychiatric disability thought to be clinically significant in the opinion of the investigator precluding informed consent or interfering with compliance