PREOPANC-6 study: dendritic cell immunotherapy after FOLFIRINOX chemotherapy in patients with resectable pancreatic cancer

Other illness

• At registration: a. Metastatic or locally advanced (unresectable) pancreatic cancer according to the DPCG criteria. b. Resectable pancreatic cancer with a CA19-9 < 500 kU/L at registration, unless predefined exception criteria (e.g. CA19-9 non-producer with PET-CT showing no distant metastases and no metabolic progression) are met and eligibility is confirmed by the central study team.
• Has a known additional malignancy that is progressing or has required active treatment within the past two years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast cancer, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has active autoimmune disease that has required systemic treatment in the past two years (i.e. with the use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen or known active Hepatitis C virus infection.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Lab values

• Has a history of current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation for the entire duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study or within 12 months after the last administration of study treatment
  • At inclusion: Registered patients are excluded from randomisation if, during neoadjuvant FOLFIRINOX: a. they develop RECIST-defined progressive disease (see 11.3.2.3); or b. they fail to demonstrate a CA19-9 response compared with baseline values or have CA19-9 levels > 500 kU/L at screening, unless predefined exception criteria apply
  • Has had an allogeneic tissue/solid organ transplant.
  • Ampullary or distal bile duct cancer.
  • Severe concomitant systemic disorders that would compromise the safety of the patient or their ability to complete the study at the discretion of the investigator.
  • A WOCPB who has a positive urine pregnancy test at screening. A serum pregnancy test will be performed if the urine test cannot be confirmed as negative.
  • Current or previous use of autologous DC therapy or anti-tumour vaccinations.
  • A known allergy or hypersensitivity to the study drug or any study drug excipients.
  • History of life-threatening toxicity related to prior immune therapy that wasn’t manageable by the standard of care treatment.
  • Current use of steroids (or other immunosuppressive agents). Patients must have discontinued treatment for at least six weeks and not use such therapy during the study.

Other

• Active or inadequately treated syphilis (Lues).

• At registration: ABC borderline resectable pancreatic cancer, histologically or cytologically confirmed. ABC borderline is defined as resectable pancreatic cancer with a CA-19.9 level > 500 kU/L at diagnosis or borderline resectable pancreatic cancer. Resectability criteria are defined by the DPCG criteria.
• Laboratory tests: ASAT/ALAT <5xULN (upper limit of normal), bilirubin <1.5xULN, Lactate dehydrogenase value < ULN and albumin value > 30.
• Women of childbearing potential (WOCB) must have a negative serum pregnancy test at screening. They must be willing to use an effective contraceptive method (intrauterine devices, hormonal contraceptives, contraceptive pill, implants, transdermal patches, hormonal vaginal devices, infusions with prolonged release) or true abstinence (when this is in line with the preferred and usual lifestyle*) during the study and for at least 12 months after the last study drug administration. *True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (such as calendar, ovulation, symptothermal, and post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Men must be willing to use an effective contraceptive method (e.g. condom, vasectomy) during the study and for at least 12 months after the last study drug administration.
• Ability to return to the hospital for adequate follow-up as required by this protocol.
• Written informed consent according to ICH-GCP.
• Inclusion and randomisation: Borderline resectable or resectable tumours according to the DPCG criteria. CA-19.9 levels of no more than 500 kU/L at the time of screening, and a valid reduction during neoadjuvant FOLFIRINOX according to the treating physician. Predefined exceptions apply for CA19-9 non-producers with PET-CT showing no metabolic progression, and for patients with CA19-9 levels above 500 kU/L who have demonstrated a valid reduction during FOLFIRINOX and are deemed clinically eligible by the treating physician, subject to approval after consultation with the central study team.
• Patients must be at least 18 years old and be able to give written informed consent.
• WHO performance status 0-1.
• Patients must be able to undergo surgery.
• Patients must have normal organ function and adequate bone marrow reserve: absolute neutrophil count > 1.0 x 109/l, total leucocyte count ≥ 3.0 x 109/l, platelet count > 100 x 109/l, renal function E-GFR ≥ 50 ml/min, and Hb > 6.0 mmol/l.