Adjuvant Trial in Pancreatic Neuroendocrine Tumors

Prior treatment

• Neoadjuvant treatment or treatment with chemotherapy regimen used for another malignancy
• Current treatment with another investigational drug
• Unrecovered toxicity from surgery
• Recent or concomitant treatment with brivudine

Other illness

• PanNET arising in a genetic syndrome with other NETs already diagnosed (NF1, VHL or MEN)
• History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least five years
• Active or suspected acute or chronic uncontrolled disease that would impart, in the judgment of the Investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the Investigator, would make the patient inappropriate for entry into this study
• Hypersensitivity to Capecitabine or Temozolomide or to any of the excipients

Lab values

• Severe renal insufficiency (measured GFR according to MDRD \< 30 ml/mn or nephrotic syndrome) or hepatic insufficiency (ALT / AST \> 2.5 x ULN or ALT/AST \> 5 x ULN if liver function abnormalities are due to the underlying malignancy and/or total serum bilirubin \> 2.5 x ULN)
• Serum albumin \< 3.0 g/dL unless prothrombin time is within the normal range

Age

• Age \< 18 years

Other

• Poorly differentiated tumours (NEC)
• Mixed NeuroEndocrine Non NeuroEndocrine tumors (MiNEN)
• Pregnant women or breastfeeding women
• ECOG performance status \> 1
• Dihydropyrimidine dehydrogenase (DPD) deficiency or not done

• Pathologically proven well differentiated neuro-endocrine tumour of the pancreas by local teams
• Availability of the primary tumor specimen, allowing accurate WHO classification and determination of MGMT status
• Stage I-III based ENETS-UICC 8th classification
• Early postoperative context (≤ 4 months)
• R0 resection
• Absence of distant metastasis or local tumor remnant as defined by a negative post-operative thorax CT and -abdomen CT or MRI and negative (best of DOTA-peptide 68Ga or, FDG) PET imaging if performed preoperatively
• ECOG 0-1
• No prior systemic therapy
• Intermediate to high risk of recurrence as defined by the following situations:
  • Ki67 ≥ 10% (i.e.: Grade 3 or high Ki67 Grade 2)
  • Ki67 5-9% AND (tumor size \> 3 cm OR Node positive)
  • Ki67 3-5% AND tumor size \> 3 cm AND Node positive
  • Ki67 \< 3% AND tumor size \> 3 cm AND Node positive AND (Vascular Emboli OR perineural invasion)
• Age ≥ 18 years at the time of consent, no superior limit
• Adequate bone marrow reserve (hemoglobine \> 8 g/dL, absolute neutrophils count ≥ 1500/mm³ and platelets ≥ 80 000/mm³)
• Effective contraception
• Written, dated and signed informed consent by the patient prior to any specific protocol procedure
• Ability to comply with the protocol procedures
• Patient affiliated to a social security system or beneficiary of the same