Adjuvant Trial in Patients With Resected PDAC Randomized to Allocation of Oxaliplatin- or Gemcitabine-based Chemotherapy by Standard Clinical Criteria or by a Transcriptomic Treatment Specific Stratification Signature

Summary

This is a multicentre open labelled phase III adjuvant trial of disease-free survival in patients with resected pancreatic ductal adenocarcinoma randomized to allocation of oxaliplatin- or gemcitabine-based chemotherapy by standard clinical criteria (control arm) or by a transcriptomic treatment specific stratification signature or TSS (test arm).

Interventions

• Oxaliplatin · DRUG

  85 mg/m2 D1 over 2 hours every; 14 days, 12 cycles, 24 weeks

• Irinotecan · DRUG

  150 mg/m2 D1 over 90 minutes to begin 30 min after the Folinic acid infusion is started; every 14 days, 12 cycles, 24 weeks

• Folinic acid · DRUG

  400 mg/m2 (racemic mixture) (or 200 mg/m2 if L-folinic acid is used), IV infusion over 2 hours; every 14 days, 12 cycles, 24 weeks

• 5-fluorouracil · DRUG

  2.4 g/m2 IV continuous infusion over 46 hours (1200 mg/m2/ day); every 14 days, 12 cycles, 24 weeks

• Gemcitabine · DRUG

  1000mg/m2 is given as an IV infusion over 30 minutes; on day 1, 8 and 15 out of 28 days (= 1 cycle); Repeated 6 times (i.e., 6 cycles) for 24 weeks

• Capecitabine · DRUG

  1660mg/m2/day in two divided doses administered orally for 21 days followed by 7 days' rest (one cycle) for six cycles i.e. 24 weeks

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion Criteria

1. Histologically proven pancreatic ductal adenocarcinoma including variants, and pancreatic acinar cell carcinoma.
2. Patient had provided tumour tissue at resection for RNAseq.
3. Macroscopically complete resection (R0 or R1 resection).
4. Female and male Patients aged from 18 to 79 years.
5. WHO performance status 0-1.
6. No prior radiotherapy and no previous chemotherapy for pancreatic cancer.
7. Full recovery from surgery and patient able to receive chemotherapy: adequate oral nutrition of ≥ 1500 calories per day and free of significant nausea and vomiting.
8. Adequate hematologic function: Absolute neutrophil count ≥ 1,500 cells/mm3, platelets ≥ 100,000 cells/mm3 and haemoglobin ≥ 8 g/L (transfusion permitted).
9. Serum total bilirubin ≤ 1.5 times the institutional upper limit of normal.
10. Creatinine clearance ≥ 50 mL/min.
11. Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use highly effective methods of contraception during the study and for 6 months after the last study treatment for women and 6 months for men.
12. Intended interval since surgery between 21 and 84 days at date of randomization.
13. Public or private health insurance cover.
14. Ability of subject to understand character and individual consequences of the clinical trial.
15. Not legally incapacitated.
16. Written informed consent.

Exclusion Criteria

1. Solid pseudopapillary neoplasm, neuroendocrine neoplasm, pancreatoblastoma, bile duct cancer, and ampullary cancer.
2. Distant metastases, including ascites or malignant pleural effusion.
3. Macroscopic incomplete tumour removal (R2 resection).
4. Post-operative CA 19-9 \> 180 U / ml before randomization on study.
5. Cardiomyopathy or congestive heart failure, NYHA III-IV or coronary heart disease symptoms.
6. Major comorbidity that may preclude the delivery of treatment or known active infection (HIV or untreated chronic hepatitis B or active hepatitis C) or uncontrolled diabetes.
7. Pre-existing neuropathy, Gilbert's disease or known genotype UGT1A1\*28 /\*28.
8. Inflammatory disease of the colon or rectum, or intestinal obstruction, or severe postoperative uncontrolled diarrhoea.
9. Known severe dihydropyrimidine dehydrogenase (DPD) deficiency (activity score \<1). There are clear guidelines for dose reductions for patients with a score of 1 and 1,5 (2 is normal activity)
10. Pregnancy and lactation.
11. Participation in other clinical trials or observation period of competing trials, respectively.
12. History of hypersensitivity or other known contraindication to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
13. Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix or bladder, or low/intermediate risk prostate cancer (Gleason score ≤7) with normal PSA levels.
14. Any other concurrent antineoplastic treatment including irradiation

Sites (33)

• Universitätsklinikum Aachen, Studienzentrum Viszeralmedizin Klinik für Allgemeine-, Viszeral und Transplatationschirurgie, Aachen, Germany
• Universitätsklinikum Augsburg, III. medizinische Klinik, Augsburg, Germany
• St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Abteilung für Hämatologie, Onkologie und Palliativmedizin, Studienambulanz, Bochum, Germany
• Universitätsklinikum Bonn, Chirurgische Abteilung, Bonn, Germany
• DIK Deggendorf, Onkologische Ambulanz, Deggendorf, Germany
• Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Germany
• Universitätsklinikum Erlangen, Chirurgische Klinik Zentrum für klinische Studien, Erlangen, Germany
• Universitätsklinikum Frankfurt, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie,, Frankfurt, Germany
• Universitätsklinikum Freiburg, Klinik für Allgemein und Viszeralchirurgie, Abteilung Chirurgie, Freiburg im Breisgau, Germany
• Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin I, Halle, Germany
• Universitätsklinikum Hamburg Eppendort, Zentrum für operative Medizin, Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Hamburg, Germany
• Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Hanover, Germany
• Universitätsklinikum Heidelberg, Abteilung für Allgemein-, Viszeral- und Transplantationschirurgie und Nationales Zentrum für Tumorerkrankungen, Medizinische Onkologie, Heidelberg, Germany
• Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II und Klinik für Allgemeine Viszeral Gefäß und Kinderchirurgie, Homburg/Saar, Germany
• Univeristätsklinikum Jena, Jena, Germany
• UKSH Campus Kiel, Medizinische Klinik II, Kiel, Germany
• Universität Leipzig, Medizinische Fakultät, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Leipzig, Germany
• Universitätsklinikum Schleswig-Holstein, Klinik für Chirurgie, Onkologisches Zentrum Campus Lübeck, Lübeck, Germany
• Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. medizinische Klinik, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Mainz, Germany
• Universitätsklinikum Mannheim, II. medizinische Klinik, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Ernährungsmedizin, Mannheim, Germany
• Universitätsklinikum Marburg, Klinik für Innere Medizin, Gastroenterologie, Stoffwechsel und Endokrinologie, Marburg, Germany
• Klinikum der Universität München, AG Onkologie der Med Klinik III, München, Germany
• Klinikum Rechts der Isar der TU München, Klinik und Poliklinik für Chirurgie, München, Germany
• Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg, Germany
• Universitätsmedizin Rostock, Klinik III (Hämatologie, Onkologie, Palliativmedizin), Zentrum für Innere Medizin, Rostock, Germany
• Caritasklinikum Saarbrücken St. Theresia, Saarbrücken, Germany
• Universitätsklinikum Ulm, Klinik für Innere Medizin I Gastroenterologie-Endokrinologie-, Nephrologie-, Ernährung und Stoffwechselkrankheiten, Ulm, Germany
• Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Zentrum für Innere Medizin, Würzburg, Germany
• Centralsjukhuset, Karlstad, Sweden
• Universitetssjukhuset, Linköping, Sweden
• Skånes universitetssjukhus, Lund, Sweden
• Norrlands universitetssjukhus, Umeå, Sweden
• Akademiska sjukhuset, Uppsala, Sweden