The addition of regional hyperthermia to standard chemotherapy (gemcitabine) in an adjuvant setting may improve the outcome of patients with pancreatic cancer. The present trial is performed in order to confirm the hypothesis that the addition of regional hyperthermia (RHT) to gemcitabine standard therapy (G + RHT) for pancreatic cancer patients after R0/R1-tumor resection is superior to gemcitabine standard therapy alone (G).

• Device: Gemcitabine + regional hyperthermia
  Gemcitabine: 1000 mg/m² as iv-infusion on days 1, 8 and 15 of each course Regional hyperthermia: 60 minutes / 42˚C on days 2, 9, and 16 of each course
• Drug: Gemcitabine
  Gemcitabine: 1000 mg/m² as iv-infusion on days 1, 8 and 15 of each course

• Active Comparator: Gemcitabine
  Gemcitabine: 1000 mg/m² as iv-infusion on days 1, 8 and 15 of each course
  Intervention: Drug: Gemcitabine
• Experimental: Gemcitabine + regional hyperthermia
  Gemcitabine: 1000 mg/m² as iv-infusion on days 1, 8 and 15 of each course Regional hyperthermia: 60 minutes / 42˚C on days 2, 9, and 16 of each course
  Intervention: Device: Gemcitabine + regional hyperthermia

Inclusion Criteria:

1. any ductal adenocarcinoma of the pancreas confirmed by histology
2. previous R0 or R1 resection of pancreatic tumor with a standardized procedure
3. no other previous or concomitant treatment of pancreatic carcinoma like radiation, chemotherapy or immunotherapy
4. no macroscopic manifestation of pancreatic cancer detectable by CT/MRT after surgery
5. postoperative tumor marker (CEA/CA19-9) <= 2.5 x upper limit of normal (ULN) to be documented within 1 week prior to randomization
6. performance status ECOG 0-2

7. adequate bone marrow function defined as

   • leucocytes >= 3.5 x 109/L
   • thrombocytes >= 150 x 109/L
   • hemoglobin >= 9 g/dl documented within 1 week prior to randomization

8. adequate renal function defined as

   • serum creatinine <= 1.5 ULN
   • calculated GFR >= 60 mL/min

9. adequate coagulatory function defined as

   • Quick-value >= 70%
   • aPTT <= 1.5 x ULN documented within 1 week prior to randomization
10. transaminases (AST, ALT) <= 3xULN and bilirubin <= 2xULN
11. between at least 18 years and 75 years of age
12. women with childbearing potential and fertile men must use adequate contraceptive measures during and for at least 3 months after completion of trial therapy (Adequate methods for women are oral contraceptives with estrogen and progesterone, vaginal rings, contraceptive patches, estrogen-free ovulation inhibitors, intrauterine devices with progesterone, 3-month injections with depot progesterone, implants setting free progesterone, abstinence or sterilization (vasectomy) of the male partner. Men must use condoms).
13. women with childbearing potential must have a negative pregnancy test within 1 week prior to randomization (postmenopausal women with amenorrhea for more than 1 year are regarded as having no childbearing potential)
14. documentation of written informed consent

Exclusion Criteria:

1. cystic carcinoma of the pancreas
2. periampullary cancer
3. presence of an active infection grade 3 or higher
4. other severe disease which could impair the patient's ability to participate in the trial according to the investigator's opinion
5. pregnant or breastfeeding women
6. contraindication with regard to standard gemcitabine
7. severe, non-healing wounds, ulcers or bone fractures
8. participation in another clinical trial during this trial or within 4 weeks prior to randomization
9. past or current abuse of illegal or legal drugs or alcohol
10. other primary malignant diseases in the medical history during the last 5 years (exceptions: carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin).
11. permanent cardiac pacemaker
12. treatment with regional hyperthermia not possible for technical reasons (e.g. metal implant, gross adiposity)
13. cirrhosis of liver (Child index B and C)
14. current severe coronary heart disease or heart insufficiency (NYHA class III and IV)

• European Society for Hyperthermic Oncology
• Institute for Medical Informatics, Biometry and Epidemiology, Munich
• ClinAssess GmbH, Leverkusen, Germany