Autologous human adipose perivascular stromal cells genetically modified to secrete soluble tumour necrosis factor-related apoptosis-inducing ligand for Pancreatic ductal adenocarcinoma | Locally advanced non-resectable pancreatic adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Patients with confirmed pancreatic ductal adenocarcinoma\n- Patient older than 18 years of age\n- Adequate hepatic and kidney function\n- Willingness and ability to comply with the scheduled visits, treatment plan, imaging procedures, laboratory tests and other study procedures, including lipoaspirate collection (liposuction)\n- Safe hematologic profile\n- Negative serum pregnancy test for females of childbearing potential within days of starting treatment\n- Patients with no evidence of peritoneal or hematogenous metastasis\n- Patients classified as non-resectable locally advanced pancreatic carcinoma (LAPC) based on imaging (TC and NMR), on multidisciplinary staff evaluation by at least an oncologist, radiologist and a qualified digestive surgeon and accounting for AJCC/UICC TNM and clinical staging\n- Measurable tumor according RECIST criteria v 1.1\n- Low tumor burden with at least one lesion equal/less than 3,5 cm that is suitable for US guided injection (and needle biopsy)\n- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2\n- Patients must be eligible for chemotherapy treatment (based on standard of care)"}

Exclusion criteria

• {"criterion_text":"- Patient with pancreatic cystic tumor or pancreatic pseudocyst\n- Irreversible cardiac arrhythmias requiring permanent medication\n- Heart insufficiency (> grade II, New York Heart Association NYHA criteria)\n- History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris\n- Uncontrolled hypertension\n- Other malignancies within the past 2 years (not including basal cell carcinoma of the skin, prostate cancer or in situ cervix carcinoma, in situ melanoma)\n- Active autoimmune disease\n- Use of any investigational agents within 21 days from the administration of study treatment\n- Patient has had major open surgery within the 3 months prior to the administration of study treatment\n- Uncontrolled intercurrent illness including but not limited to psychiatric illness/social situations that in the opinion of the Investigator would compromise compliance of study requirements or put the patient at unacceptable risk\n- Suspected or known allergy or hypersensitivity to fluoroquinolones including but not limited to ciprofloxacin\n- Patient with pancreatic tumor different from adenocarcinoma (endocrine, metastases)\n- Suspected or known allergy or hypersensitivity to protamine sulfate or protamine containing products. Including but not limited to patients who have previously undergone procedures such as coronary angioplasty or cardio-pulmonary bypass, which may involve the use of protamine, diabetics who have been treated with protamine insulin, patients allergic to fish, and men who have undergone a vasectomy or are infertile and may have antibodies to protamine\n- Patients with unknown stage or recurrent pancreatic cancer\n- Patients with immunosuppression or susceptibility to viral infection\n- Patients with HIV, hepatitis B, hepatitis C, HTLV-I/II, Treponema Pallidum infections\n- Patients with liver cirrhosis or other documented liver diseases\n- Patient contraindication to use chemoterapy treatments\n- Previous radiotherapy and/or chemotherapy for PDAC\n- Previous haematopoietic stem cell or organ transplantation"}

Primary endpoints

• {"endpoint_text":"- To investigate the safety of intratumoral injections of the gene therapy product RR001 administered by US guided injection in combination with standard of care therapy based on GEM/Nab-PTX","definition_or_measurement_approach":""}
• {"endpoint_text":"- To establish the MTD and RP2D of intratumoral injections of RR001 after three dose levels delivery in combination with standard of care therapy","definition_or_measurement_approach":"Determine MTD and RP2D following a three dose-level escalation scheme (dose escalation design described in protocol)."}

Secondary endpoints

• {"endpoint_text":"- To investigate the feasibility of intratumoral injections of the gene therapy product RR001 administered by US guided injection in combination with standard of care therapy based on GEM/Nab-PTX","definition_or_measurement_approach":""}
• {"endpoint_text":"- Antitumor activity: Target tumor response will be assessed by objective radiologic assessment using RECIST 1.1 criteria","definition_or_measurement_approach":"Objective radiologic assessment (CT and MRI) using RECIST 1.1 criteria."}
• {"endpoint_text":"- Response rate: the overall response rates (ORR) for objective response (complete, partial responses, stable disease, progressive disease) will be assessed by objective radiographic assessment using RECIST 1.1 criteria","definition_or_measurement_approach":"ORR assessed by radiographic evaluation per RECIST 1.1 (complete response, partial response, stable disease, progressive disease)."}
• {"endpoint_text":"- Percentage of patients successfully undergoing to surgery and percentage of pathological resection (R0 vs. R1 vs. R2)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to disease progression (TTP)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Tumor markers in serum (CEA, CA19.9 if present at the diagnosis)","definition_or_measurement_approach":"Measurement of serum tumor markers CEA and CA19.9 where present at diagnosis."}
• {"endpoint_text":"- Quality of life by scoring of quality of life according to the EORTC QLQ-C30 and QLQ-PAN26","definition_or_measurement_approach":"Quality of life assessed using EORTC QLQ-C30 and QLQ-PAN26 questionnaires."}
• {"endpoint_text":"- Progression free survival (PFS)","definition_or_measurement_approach":""}

Italy

Earliest CTIS Part Ii Submission Date

02-07-2024

Latest Decision Or Authorization Date

12-09-2025

Processing Time Days

437

Number Of Sites

1

Number Of Participants

18

Primary sponsor

Full Name

Eir Biotherapies S.r.l.

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Italy

Contract research organisations

Name

Phaidon International (Deutschland) GmbH

Responsibilities

CRA staffing

Name

Klifo A/S

Responsibilities

TMF services

Name

Pharmaceutical Development And Services S.r.l.

Responsibilities

Pharmacovigilance (PV)

Name

4S4p Consulenze S.r.l.

Responsibilities

PV Oversight

Name

Aptuit (Verona) S.r.l.

Third parties

• {"country":"Germany","full_name":"Phaidon International (Deutschland) GmbH","duties_or_roles":"CRA staffing","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Denmark","full_name":"Klifo A/S","duties_or_roles":"TMF services","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Aptuit (Verona) S.r.l.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Pharmaceutical Development And Services S.r.l.","duties_or_roles":"Pharmacovigilance (PV)","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"4S4p Consulenze S.r.l.","duties_or_roles":"PV Oversight","organisation_type":"Non-Pharmaceutical company"}