OLAPARIB for Pancreatic adenocarcinoma (advanced/metastatic) | PALB2-mutated pancreatic cancer

Inclusion criteria

• {"criterion_text":"- Must be over 18 years of age\n- You must have histologically or cytologically confirmed pancreatic adenocarcinoma\n- Must have advanced disease (unresectable or metastatic)\n- Must have carried out genetic testing with evidence of a pathogenetic (C5) or probably pathogenetic (C4) mutation of PALB2 at the germinal or somatic level\n- Must have received at least one line of treatment for advanced (locally advanced or metastatic) disease.\n- Must have at least one measurable lesion according to RECIST 1.1 criteria by contrastenhanced CT (or MRI if the patient is allergic to the CT contrast medium).\n- Must have a life expectancy greater than 16 weeks according to the investigator's clinical judgment\n- Must have an ECOG PS equal to 0 or 1, established within 3 days of starting treatment\n- Must have adequate organ function at baseline (within 10 days of starting treatment)\n- Women of childbearing potential (WOCBP) must have a negative pregnancy test (urine or serum) in the screening period (within 24 hours of the first treatment dose) and confirmed on day 1 of each cycle. Male and female subjects of childbearing age must accept the use of an effective contraceptive method during treatment and for at least 1 month after (women) and 3 months after (men). Breastfeeding is not allowed during the study.\n- The patient (or legal representative) must have read and understood the informed consent and must have provided written informed consent."}

Exclusion criteria

• {"criterion_text":"- History of other malignant tumors in progress or requiring active treatments except: non-melanomatous skin carcinoma, ductal carcinoma in situ (DCIS); cervical cancer in situ; endometrial cancer G1, stage I; other solid tumors treated curatively without evidence of disease for> = 5 years\n- Presence of myelodysplastic syndrome / acute myeloid leukemia or suggestive elements for MDS / AML\n- Presence of symptomatic / uncontrolled CNS disease or presence of carcinomatous meningitis.\n- Weight loss> 10% during screening and / or decline in PS ECOG to> 1 between the baseline visit and 72 hours prior to the start of therapy\n- Presence of active infection that requires the initiation of systemic therapy\n- Presence of psychiatric pathology or substance abuse that may interfere with treatment compliance\n- Persistent CTCAE toxicity> Grade 2 caused by previous treatments with the exception of alopecia. Patients with CTCAE <= 2 sensorineural neuropathy due to previous oxaliplatin treatments may be included after consultation with the investigator.\n- Patients considered to be at high risk for uncontrollable medical events (e.g. ventricular arrhythmia, recent myocardial infarction, superior vena cava syndrome ...)\n- Inability to administer oral therapy or the presence of GI disorders that prevent the absorption of the study drug.\n- Immunocompromised patients (e.g. HIV)\n- Active hepatitis (B or C)\n- Presence of a benign variant or variant of uncertain significance (VUS) of PALB2\n- Presence of other histology than ductal adenocarcinoma of the pancreas (e.g. neuroendocrine, adenosquamous, etc.)\n- Presence of bone disease alone as the site of metastatic disease\n- Major surgery within two weeks of starting treatment\n- Previous treatment with PARP inhibitor, including Olaparib\n- Previous systemic therapy, target therapy or radiotherapy (with the exception of palliation) within 3 weeks of starting the study\n- Treatment with potent CYP3A inhibitors (see protocol). A 2-week washout period is required\n- Treatment with potent CYP3A inducers (see protocol). A washout period of 5 weeks for enzalutamide and phenobarbital and 3 weeks for the other agents.\n- Whole blood transfusion in the last 120. Transfusion of platelets or concentrated red blood cells are allowed (no later than 28 days before the start of treatment)\n- Receiving allogeneic bone marrow transplant or double umbilical cord blood transplant (dUCBT)\n- Concomitant participation in another interventional clinical study or within the last 4 weeks\n- Known hypersensitivity to olaparib or to any of the excipients of the product\n- ECG indicating uncontrolled cardiac abnormalities or potentially reversible cardiac conditions in the opinion of the investigator\n- Any condition, therapy or laboratory alteration that may confuse trial data, interfere with trial participation, or make trial participation not the best treatment option for the patient\n- Involvement in planning / conducting the study\n- Patient deemed not compliant by the investigator\n- Patients pregnant woman, in the course of breastfeeding or who are considering a conception (also valid for male patients)."}

Primary endpoints

• {"endpoint_text":"- Objective response rate (ORR), defined as the percentage of patients with response of either CR or PR.","definition_or_measurement_approach":"ORR defined as the percentage of patients with response of either CR (complete response) or PR (partial response); radiological re-evaluation according to RECIST 1.1 criteria (as described in main objective)."}

Secondary endpoints

• {"endpoint_text":"- Assessment of PFS (progression-free survival), DOR (duration of response), DCR (disease control rate), OS (overall survival), safety and tolerability of treatment. Furthermore, the quality of life will be assessed through the EORTC QLQ-C30 questionnaire.","definition_or_measurement_approach":"PFS, DOR, DCR, OS measured per standard oncology endpoints (radiological assessments per RECIST 1.1); safety/tolerability via CTCAE; quality of life via EORTC QLQ-C30 questionnaire."}

Italy

Earliest CTIS Part Ii Submission Date

11-10-2024

Latest Decision Or Authorization Date

10-12-2025

Processing Time Days

425

Number Of Sites

4

Number Of Participants

16

Primary sponsor

Full Name

Azienda Ospedaliero Universitaria Di Modena

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"AstraZeneca S.p.A.","duties_or_roles":"Source of monetary support (listed under sourceOfMonetarySupport)","organisation_type":""}