Capecitabine for Pancreatic ductal adenocarcinoma (resectable)

Inclusion criteria

• {"criterion_text":"- 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)\n- Trial part II: No evidence of postoperative tumor recurrence/metastases by radiological assessment\n- Trial part II: Clinically eligible for all adjuvant treatment regimens foreseen in this trial\n- Trial part II: Sufficient convalescence from surgery and revision surgeries if applicable\n- Trial part II: Postoperative Ca19-9 <180 U/ml (starting from POD 14)\n- Trial part II: Organoid-based chemotherapy recommendation available\n- Trial part II: Creatinine clearance ≥ 30 ml/min\n- Trial part II: Serum total bilirubin level 1.5 - 3 x ULN\n- Trial part II: ALT and AST ≤ 2.5 x ULN\n- 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\n- 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.\n- General: ECOG performance status 0-1\n- General: Age ≥ 18 years\n- 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\n- Trial part I: No evidence of metastases to distant organs (e.g. liver, peritoneum, lung)\n- Trial part I: Suitable for adjuvant treatment with mFOLFIRINOX\n- Trial part II: Histologically confirmed PDAC\n- Trial part II: R0 or R1 resection\n- Trial part II: Start of adjuvant chemotherapy within 12 weeks after tumor resection"}

Exclusion criteria

• {"criterion_text":"- General: R2 resection or metastatic PDAC by radiological criteria or macroscopic aspect intraoperatively\n- General: Known dihydropyrimidine dehydrogenase (DPD) deficiency (will be tested in all patients receiving fluoropyrimidine treatment)\n- General: Severe non-healing wounds, ulcers or bone fractures\n- General: Evidence of bleeding diathesis or coagulopathy\n- 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)\n- 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\n- General: Patients with known allergies to the trial drugs or to any of its excipients\n- General: Clinically relevant interstitial lung disease, e.g. non-infectious pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease\n- 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)\n- 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\n- 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\n- General: Neoadjuvant treatment for PDAC\n- Trial part II: Patients not treated according to recommendation of Organoid Board\n- General: Chronic infectious diseases, immune deficiency syndromes, including evidence of clinically relevant, active hepatitis B, C or HIV infection\n- General: Premalignant hematologic disorders, e.g. myelodysplastic syndrome\n- General: Disability to understand and sign written informed consent document\n- 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\n- General: Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrolment\n- 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)\n- General: Pre-existing neuropathy > grade I (NCI CTCAE V 5.0)"}

Primary endpoints

• {"endpoint_text":"- Trial part I: Feasibility of treatment selection by an organoid-based approach in the adjuvant setting within 12 weeks after surgery in more than 60% of the resected PDAC.","definition_or_measurement_approach":"Feasibility measured as proportion of resected PDAC patients for whom organoid-based treatment selection is completed within 12 weeks after surgery; target >60%."}
• {"endpoint_text":"- Trial part II: DFS at 18 months from start of organoid-based adjuvant treatment.","definition_or_measurement_approach":"Disease-free survival measured at 18 months from start of organoid-based adjuvant treatment."}

Secondary endpoints

• {"endpoint_text":"- Trial part I: Organoid establishment in more than 75% of the resected PDAC","definition_or_measurement_approach":"Proportion of resected PDAC samples in which organoids are successfully established; target >75%."}
• {"endpoint_text":"- Trial part I: Organoid expansion and characterization in more than 60% of the resected PDAC","definition_or_measurement_approach":"Proportion of established organoids that can be expanded and characterized; target >60%."}
• {"endpoint_text":"- Trial part I: Rate of organoid-based change of adjuvant treatment regimen from standard mFOLFIRINOX treatment","definition_or_measurement_approach":"Proportion of patients for whom organoid results lead to a change from standard mFOLFIRINOX regimen."}
• {"endpoint_text":"- Trial part I: Comparison of organoid establishment, expansion and characterization as well as treatment outcome between the different sites establishing organoids","definition_or_measurement_approach":"Site-level comparison of organoid laboratory performance and associated clinical outcomes."}
• {"endpoint_text":"- Trial part II: Time from surgery to start of adjuvant treatment","definition_or_measurement_approach":"Measured interval in days from surgical resection to initiation of adjuvant therapy."}
• {"endpoint_text":"- Trial part II: Rate of patients receiving adjuvant treatment","definition_or_measurement_approach":"Proportion of enrolled patients who receive any adjuvant therapy."}
• {"endpoint_text":"- Trial part II: DFS in organoid-based treatment selection with and without mFOLFIRINOX","definition_or_measurement_approach":"Disease-free survival comparison between organoid-selected treatment arms with and without mFOLFIRINOX."}
• {"endpoint_text":"- Trial part II: OS in organoid-based treatment selection with and without mFOLFIRINOX","definition_or_measurement_approach":"Overall survival comparison between organoid-selected treatment arms with and without mFOLFIRINOX."}
• {"endpoint_text":"- Trial part II: Comparison of DFS and OS by organoid-based adjuvant treatment with historical controls from the PRODIGE 24 trial","definition_or_measurement_approach":"Comparison of DFS and OS outcomes against historical control data from the PRODIGE 24 trial."}
• {"endpoint_text":"- Trial part II: Correlation of CT imaging (radiomics) with R0 resection rate, DFS, OS, Ca19-9 and biomarker behaviour","definition_or_measurement_approach":"Correlation analyses between radiomics features and surgical/pathological outcomes, survival endpoints, CA19-9 and biomarker changes."}
• {"endpoint_text":"- Trial part II: Health related quality of life (EORTC QLQ-PAN26, QLQ-C30 questionnaires)","definition_or_measurement_approach":"Assessment of health-related quality of life using EORTC QLQ-PAN26 and QLQ-C30 instruments."}
• {"endpoint_text":"- Trial part II: Safety and Toxicity of organoid-based adjuvant treatment","definition_or_measurement_approach":"Safety and toxicity assessed by standard adverse event reporting and CTCAE criteria."}

Germany

Earliest CTIS Part Ii Submission Date

12-06-2025

Latest Decision Or Authorization Date

01-07-2025

Processing Time Days

19

Number Of Sites

7

Number Of Participants

92

Primary sponsor

Full Name

Universitaetsklinikum Ulm AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Universitaetsklinikum Ulm AöR","duties_or_roles":"codes: 1,12,6,7,8","organisation_type":"Hospital/Clinic/Other health care facility"}