Using lab-grown mini-tumors to guide treatment after pancreatic cancer surgery

Who can take part

• General: Signed informed consent according to ICH/GCP and national/local regulations (informed consent is given for both part I and part II of the trial at enrolment; participation in translational research is voluntary)
• Trial part II: No evidence of postoperative tumor recurrence/metastases by radiological assessment
• Trial part II: Clinically eligible for all adjuvant treatment regimens foreseen in this trial
• Trial part II: Sufficient convalescence from surgery and revision surgeries if applicable
• Trial part II: Postoperative Ca19-9 <180 U/ml (starting from POD 14)
• Trial part II: Organoid-based chemotherapy recommendation available
• Trial part II: Creatinine clearance ≥ 30 ml/min
• Trial part II: Serum total bilirubin level 1.5 - 3 x ULN
• Trial part II: ALT and AST ≤ 2.5 x ULN
• Trial part II: White blood cell count ≥ 3.5 x 10^6/ml, neutrophil granulocytes count ≥ 1.5 x 10^6/ml, platelet count ≥ 100 x 10^6/ml
• Trial part II: Women of Childbearing Potential (WOCBP, defined as not postmenopausal and not surgically or congenitally sterile) whose male partners are potentially fertile (e.g. no vasectomy) or males that are potentially fertile with WOCBP-partner must use highly effective contraception methods for the duration of the trial and for at least 15 months (male or female) after last dose of trial drug (IMP). Postmenopausal is defined as no menses for 12 months without an alternative medical cause. Highly effective birth control methods that result in a failure rate of less than 1% per year include hormonal contraception, intrauterine device, bilateral tubal occlusion, vasectomized partner. Sexual abstinence is only considered a highly effective method if defined as refraining from heterosexual intercourse in the defined period. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the trial and the preferred and usual lifestyle of the patient
• General: ECOG performance status 0-1
• General: Age ≥ 18 years
• Trial part I: Suspected pancreatic ductal adenocarcinoma (PDAC), resectable according to NCCN criteria, Ca19-9 <500 U/ml (without relevant cholestasis), ≤ cT3 with no prior tumor specific treatment
• Trial part I: No evidence of metastases to distant organs (e.g. liver, peritoneum, lung)
• Trial part I: Suitable for adjuvant treatment with mFOLFIRINOX
• Trial part II: Histologically confirmed PDAC
• Trial part II: R0 or R1 resection
• Trial part II: Start of adjuvant chemotherapy within 12 weeks after tumor resection

Who cannot take part

• General: R2 resection or metastatic PDAC by radiological criteria or macroscopic aspect intraoperatively
• General: Known dihydropyrimidine dehydrogenase (DPD) deficiency (will be tested in all patients receiving fluoropyrimidine treatment)
• General: Participation in another clinical trial affecting endpoints (within the last 14 days prior to enrolment or 5 plasma half-lives of the used investigational drug, whatever is longer)
• General: Any psychological, familial, sociological or geographical condition potentially compromising compliance with the trial protocol and the follow-up schedule; those conditions should be discussed with the patient prior to enrolment in the trial
• General: Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrolment
• General: Evidence of bleeding diathesis or coagulopathy
• General: Patients with known allergies to the trial drugs or to any of its excipients
• General: Clinically relevant interstitial lung disease, e.g. non-infectious pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease
• General: Chronic infectious diseases, immune deficiency syndromes, including evidence of clinically relevant, active hepatitis B, C or HIV infection
• General: Premalignant hematologic disorders, e.g. myelodysplastic syndrome
• General: Past (last 3 years) or current history of malignancies except for the indication under this trial and curatively treated: a. Basal and squamous cell carcinoma of the skin | b. In-situ carcinoma of the cervix | c. Other malignant disease without recurrence after at least 2 years of follow-up
• General: History of or evidence upon physical examination of CNS disease unless adequately treated (e.g. primary brain tumor, seizure not controlled with standard medical therapy or history of stroke)
• General: Patients not receiving therapeutic anticoagulation must have an INR ≤ 1.4 and PTT ≤ 40 sec within 28 days prior to enrolment. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution)
• General: Pregnant, lactating or women of childbearing potential without a negative pregnancy test (serum) within 7 days prior to trial inclusion, irrespective of the method of contraception used
• General: Person of legal age who is incapable of comprehending the nature, significance and implications of the clinical trial and of determining his/her will in the light of these facts
• General: Severe non-healing wounds, ulcers or bone fractures
• General: Neoadjuvant treatment for PDAC
• Trial part II: Patients not treated according to recommendation of Organoid Board
• General: Disability to understand and sign written informed consent document
• General: Pre-existing neuropathy > grade I (NCI CTCAE V 5.0)