The ADAPTA Study: ADjuvant chemotherAPy After Curative Intent resecTion of Ampullary Cancer.

Background:

Ampullary adenocarcinoma(AAC) is rare. 5-year survival rates of 30% to 70% are seen after resection. This broad range of survival could be explained by the morphological heterogeneity in the three subtypes of AAC (pancreatobiliary, intestinal and mixed subtype), which complicates the prediction of individual prognosis and clinical decision making with regard to adjuvant therapy. To date there are no prospective studies to elucidate whether adjuvant chemotherapy improves survival in these patients.

Methods/design:

The ADAPTA study is a phase II prospective single arm multicenter cohort study including 200 patients with resected AAC (100 patients with intestinal subtype, and 100 with pancreatobiliary- and mixed subtype). All patients will be treated with CAPOX/ FOLFIRINOX respectively. Outcomes will be compared after propensity score matching to data of all patients in consecutive participating centers not treated according to the proposed regime.

Inclusion criteria

• Adult patients with histologically or cytologically confirmed AAC with subtyping of pancreatobiliary/mixed subtype or intestinal subtype
• After curative resection for ampullary cancer without metastatic disease.
• WHO performance status 0 or 1
• Able and willing to receive adjuvant chemotherapy
• R0/ R1 resection
• Age ≥ 18 years
• Written informed consent

Exclusion criteria

• Prior radiotherapy, chemotherapy, or resection for AAC.
• Previous malignancy (excluding non-melanoma skin cancer), unless no evidence of disease and diagnosed more than 5 years before diagnosis of AAC.
• Pregnancy.
• R2 resection.
• Adjuvant chemotherapy started more than 12 weeks after surgery (aim to start within 8 weeks)
• Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.
• Known hypersensitivity or contraindications against capecitabine, 5 FU, Irinotecan, or Oxaliplatin
• Inadequate organ functions, characterized by:

• Leucocytes (WBC) < 3.0 X 109/l
• Neutrophils < 1.500 (count per microliter of blood)
• Platelets < 100 x 109 /l
• Hemoglobin < 8 mmol/l
• Renal function: E-GFR < 50 ml/min (serum creatinine < 1.5 x UNL)
• cholestasis with elevated levels of bilirubin and/or alkaline phosphatase > 3x UNL (can be improved by biliary drainage if necessary)
• elevated transaminases (ALAT/ASAT) ≥ 5 x UNL
• hypoalbuminemia < 2.5 g/dl
• Inadequate coagulation status INR > 2 or Quick < 50%, aPTT >50 sec in the absence of any drugs interfering with coagulation such as acenocoumarin, warfarin, phenprocoumon, NMH or UFH.