Phase II/III Randomized Trial of Autologous Dendritic Cell Vaccine (MesoPher) Following FOLFIRINOX in Patients with Borderline Resectable Pancreatic Cancer
- Trial ID
- 2025-523134-28-00
- Protocol
- 14395
Trial statistics
Diseases & Conditions
Objectives
Primary objectives: Phase II evaluates whether adjuvant dendritic cell immunotherapy (MesoPher) improves progression‑free survival (PFS) according to RECIST 1.1 in patients with ABC borderline resectable pancreatic cancer; Phase III assesses the effect of MesoPher on overall survival (OS) in the same cohort.
Secondary objectives:
- Assessment of immune responses induced by MesoPher.
- Determination of disease‑free survival (DFS) per RECIST 1.1.
- Investigation of event‑free survival (EFS) per RECIST 1.1 (Phase III).
- Evaluation of quality of life using validated patient‑reported outcomes.
- Systematic monitoring of safety, tolerability and feasibility of the autologous dendritic cell product.
Participants
The trial enrolled adult patients (≥18 years) of both sexes diagnosed with borderline resectable pancreatic cancer confirmed histologically or cytologically and meeting DPCG resectability criteria; the sponsor did not provide the total number of participants. Eligibility required a WHO performance status of 0‑1, adequate organ function (e.g., ASAT/ALAT <5×ULN, bilirubin <1.5×ULN, LDH
Plans and Procedures
The PREOPANC‑6 trial is a national randomized, double‑blind, placebo-controlled phase II/III study evaluating the efficacy of autologous dendritic cells loaded with allogenic mesothelioma lysate (MesoPher) administered by intravenous infusion (25 × 10⁶ U) after neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer. After written informed consent, eligible participants undergo a screening visit to confirm histologic diagnosis, CA‑19‑9 level, organ function, and eligibility criteria; baseline assessments include imaging, laboratory tests, and quality‑of‑life questionnaires. Randomisation occurs at the post‑chemotherapy visit, and participants receive the study product or matching control on day 1 of the adjuvant period, with a second infusion at week 4. Follow‑up visits are scheduled at weeks 8, 12, and then every 12 weeks for disease assessment by RECIST 1.1, immune monitoring, safety labs, and patient‑reported outcomes. The end‑of‑study visit occurs at 36 months after randomisation or at death, whichever occurs first, and captures final survival status and long‑term safety. Primary efficacy endpoints are progression‑free survival (time from first infusion to RECIST‑defined progression or death) in phase II and overall survival in phase III. Participants are expected to remain in the trial for up to three years of follow‑up. Early discontinuation may occur due to disease progression, grade ≥ 3 treatment‑related adverse events, withdrawal of consent, intercurrent illness preventing protocol compliance, or investigator decision based on safety concerns.
Treatment
The investigational product is a personalized cellular product consisting of autologous dendritic cells loaded with allogenic allogeneic lysate of mesothelioma cell lines. Each dose contains 25 000 000 U and is supplied for intravenous infusion. The product is administered by a single intravenous infusion per the study protocol; the infusion rate and duration are defined in the clinical trial manual.
Administration is performed under aseptic conditions in a clinical setting. Participants are observed for immediate adverse reactions during and after the infusion. Compliance with the dosing schedule is documented in the case report form, and all infusion procedures are recorded to ensure adherence to the protocol.
Efficacy
The primary efficacy assessments include progression‑free survival, defined as the interval from the start of study treatment to the first documented recurrence or progressive disease according to RECIST 1.1, or death from any cause, whichever occurs first, and overall survival, defined as the time from inclusion to death due to any cause. Both endpoints are derived from serial imaging evaluations and vital status follow‑up.
Secondary efficacy evaluations comprise disease‑free survival (first documented recurrence per RECIST 1.1), event‑free survival (time from randomisation to failure to undergo surgery, disease recurrence, or death), and patient‑reported quality of life measured with the EORTC QLQ‑C30 and EORTC‑QLQ‑PAN26 questionnaires. Immune‑response assessments involve analysis of peripheral blood mononuclear cells, including NanoString nCounter gene‑expression profiling and evaluation of peripheral immune‑cell subset modulation. All laboratory and questionnaire data are collected at scheduled study visits and analysed according to the predefined statistical analysis plan.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- 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.
- 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.
Exclusion Criteria
- 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.
- 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
- 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.
- 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.
- Active or inadequately treated syphilis (Lues).
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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
- Has had an allogeneic tissue/solid organ transplant.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Not Yet Recruiting | 01 Jun 2026 | — |
| Netherlands | — | — | 143 |