FLUOROURACIL for Advanced pancreatic cancer | Pancreatic adenocarcinoma

Stratification factors

• ECOG Performance status (0 vs 1)
• Disease extension (locally advanced vs metastatic with liver metastases vs metastatic without liver metastases)

Inclusion criteria

• {"criterion_text":"- Patient able and willing to provide written informed consent and to comply with the study protocol."}
• {"criterion_text":"- Adequate renal function, i.e. serum creatinine ≤ 1.5 x institutional ULN and calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 50 mL/min."}
• {"criterion_text":"- Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy)."}
• {"criterion_text":"- No presence of complete dihydropyrimidine dehydrogenase (DPYD) enzyme deficiency (homozygous of the following DPYD polymorphisms: c1679GG, c1905+1AA, c2846TT) with DPYD gene testing mandatory at screening as per national guidelines. UDP-glucuronosyltransferase 1A1 (UGT1A1) testing is not mandatory. However, if UGT test is routinely performed in the participating centers, enrolment of patients carriers of variants of DPYD and homozygous variant UGT1A1 [7/7] has to be discussed with the Sponsor. See Appendix VI of the full protocol for details."}
• {"criterion_text":"- Women of childbearing potential must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods, as defined in Appendix V of the full protocol, during the treatment period and for at least 7 months after the last administration of study treatments."}
• {"criterion_text":"- Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women <1 year after the onset of menopause."}
• {"criterion_text":"- Men must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods, as defined in Appendix V of the full protocol, during the treatment period and for at least 7 months after the last administration of study treatments."}
• {"criterion_text":"- Participants must agree not to donate eggs/sperm for future use for the purposes of assisted reproduction during the study and for a period of 7 months after receiving the last dose of study treatment. Female and male participants should consider preservation of eggs/sperm prior to study treatment as anti-cancer treatments may impair fertility."}
• {"criterion_text":"- Subjects must be ≥18 years."}
• {"criterion_text":"- Histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic adenocarcinoma eligible for treatment in the first-line setting."}
• {"criterion_text":"- Presence of measurable or non-measurable disease assessed by CT scan and/or MRI according to RECIST 1.1 (Appendix I of the protocol). Note: any lesion which has been subjected to percutaneous therapies or radiotherapy should not be considered measurable, unless the lesion has clearly progressed since the procedure."}
• {"criterion_text":"- Availability of archival tumor sample (primary tumor or metastatic site) for biomarker analysis."}
• {"criterion_text":"- ECOG performance status of 0-1 (if age < 70 years). If age ≥70 years, ECOG PS must be 0."}
• {"criterion_text":"- Estimated life expectancy > 3 months."}
• {"criterion_text":"- Adequate baseline hematologic function characterized by the following at screening: a. Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L b. platelets count ≥ 100 × 109/L c. hemoglobin ≥ 9 g/dl. Note: prior transfusions for patients with low hemoglobin are allowed."}
• {"criterion_text":"- Adequate liver function characterized by the following at screening:a. Serum total bilirubin ≤ 1.5 × ULN and < 2 mg/dL. Note: Subjects with Serum total bilirubin ≥ 1.5 × ULN and conjugated bilirubin ≤ ULN or < 40% of total bilirubin are allowed. b. Serum transaminases (AST and/or ALT) < 3 x ULN (< 5 x ULN in presence of liver metastasis). In participants with elevated AST or ALT, the values must be stable for at least 2 week and with no evidence of biliary obstruction by imaging."}

Exclusion criteria

• {"criterion_text":"- Pancreatic neuroendocrine, acinar, squamous/adenosquamous, or islet tumors."}
• {"criterion_text":"- Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per μL or more; HIV viral load must be undetectable per standard of care assay, and they must be compliant with antiretroviral treatment."}
• {"criterion_text":"- Pregnant or breast-feeding patient, or patient planning to become pregnant within 7 months after the end of treatment."}
• {"criterion_text":"- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA > II, unstable angina pectoris, history of myocardial infarction within 3 months before study entry, significant arrhythmia)."}
• {"criterion_text":"- Presence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent."}
• {"criterion_text":"- Any serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial."}
• {"criterion_text":"- Previous or concurrent systemic (eg cytotoxic or targeted or other experimental drugs) therapy for advanced pancreatic adenocarcinoma. Note: previous (neo)adjuvant or perioperative anti-cancer therapy for non-metastatic, resectable or borderline resectable PDAC, associated with surgery on the primary tumor, is allowed if ≥ 9 months have elapsed from the last dose of therapy and documented disease progression or relapse."}
• {"criterion_text":"- Major surgery or radiation therapy performed within ≤4 weeks before randomization. Palliative radiotherapy to bone lesions is allowed if performed ≥ 2 weeks prior to start of study treatment. Patients must have recovered from any effect from major surgery."}
• {"criterion_text":"- Known allergy or hypersensitivity to study drugs and/or their excipients."}
• {"criterion_text":"- Unresolved toxicity ≥ CTCAE grade 2 attributed to any prior therapies (e.g. grade ≥2 peripheral neurotoxicity), excluding anemia or alopecia."}
• {"criterion_text":"- Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that requires directed therapy (such as radiotherapy or surgery) or increasing doses of corticosteroids 2 weeks prior to study entry. Participants with treated symptomatic brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study entry."}
• {"criterion_text":"- Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years prior to study entry except for curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, and prostate cancer."}
• {"criterion_text":"- Know active uncontrolled hepatitis B or hepatitis C. Patients with a past or resolved HBV infection are eligible. Patients with chronic disease controlled by antiviral therapy or requiring prophylactic treatment are eligible."}
• {"criterion_text":"- Chronic or current active infectious disease requiring systemic antibiotics or antifungal treatment within 2 weeks prior to enrollment."}

Primary endpoints

• {"endpoint_text":"- Overall survival (OS) i.e. the time from randomization to death or last follow-up for alive patients.","definition_or_measurement_approach":"Time from randomization to death or last follow-up for alive patients (overall survival)."}

Secondary endpoints

• {"endpoint_text":"- PFS, i.e. the time from randomization to disease progression or death from any cause TTF, i.e. time from randomization to discontinuation of treatment for any reason, including progressive disease, treatment toxicity and death.","definition_or_measurement_approach":"PFS: time from randomization to disease progression or death from any cause. TTF: time from randomization to discontinuation of treatment for any reason (progressive disease, toxicity, death)."}
• {"endpoint_text":"- ORR, i.e. the percentage of patients achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria DCR, i.e. the percentage of patients achieving a complete (CR) or partial (PR) response or a stable disease (SD), according to RECIST 1.1 criteria.","definition_or_measurement_approach":"ORR: percentage with CR or PR per RECIST 1.1. DCR: percentage with CR, PR or SD per RECIST 1.1."}
• {"endpoint_text":"- Quality of life (QoL), i.e. QoL will be estimated with EORTC QLQ-C30 and the modules PAN26, FA12, CAX24, COMU26 a will be performed with the EORTC QLQ INFO25, which is a valid self-reported instrument consisting of 25 questions. Communication between patients and professionals will be assessed with the EORT QLC COMU26.","definition_or_measurement_approach":"QoL measured using EORTC QLQ-C30 and modules PAN26, FA12, CAX24, COMU26; EORTC QLQ INFO25 for information; communication assessed by EORTC QLQ COMU26 (self-reported instruments)."}
• {"endpoint_text":"- Toxicity, i.e. the percentage of patients experiencing a specific adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0).","definition_or_measurement_approach":"Percentage of patients experiencing specific adverse events graded per NCI CTCAE v5.0."}
• {"endpoint_text":"- Proportion of patients not eligible to randomization, i.e. patients who started induction treatment but result not eligible due to i) clinical deterioration or treatment toxicity, ii) withdraw consent or iii) disease progression documented as best response, iv) other causes.","definition_or_measurement_approach":"Proportion of patients starting induction but not randomized for specified reasons (clinical deterioration, toxicity, withdrawal, progression, other)."}
• {"endpoint_text":"- Subsequent treatment line frequency, i.e. the percentage of patients who undergo a systemic treatment (excluding locoregional treatments or surgical treatment of unresectable disease) after progression to first line in both arms.","definition_or_measurement_approach":"Percentage of patients receiving subsequent systemic treatment after progression to first-line therapy (excluding locoregional/surgical treatments)."}

Italy

Earliest CTIS Part Ii Submission Date

09-12-2024

Latest Decision Or Authorization Date

16-01-2025

Processing Time Days

38

Number Of Sites

28

Number Of Participants

340

Primary sponsor

Full Name

Gruppo Oncologico Del Nord Ovest

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"Fondazione Rising Tide","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Fondazione Gono","duties_or_roles":"Monetary support","organisation_type":""}