Phase I/IIa Study: RR001 Administered Following Chemotherapy Cycles for Patients With Locally Advanced Pancreatic Carcinoma

Prior treatment

• Patient contraindication to use chemotherapy treatments
• Previous of radiotherapy and chemotherapy for PDAC
• Previous hematopoietic stem cell or organ transplantation
• Use of any investigational agents within 21 days from the administration of study treatment
• Patient has had major open surgery prior to the administration of study treatment
• 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

Other illness

• Patients with unknown stage or recurrent pancreatic cancer
• Patients with immunosuppression or susceptibility to viral infection
• Patients with HIV, hepatitis B, hepatitis C, HTLV-I/II, Treponema Pallidum infections
• Patients with liver cirrhosis or other documented liver diseases
• Irreversible cardiac arrhythmias requiring permanent medication
• Heart insufficiency (\> grade II, New York Heart Association NYHA criteria)
• History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris
• Uncontrolled hypertension
• 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).
• Active autoimmune disease
• 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
• Suspected or known allergy or hypersensitivity to fluoroquinolones including but not limited to ciprofloxacin

Other

• Patient with pancreatic cystic tumor or pancreatic pseudocyst
• Patient with pancreatic tumor different from adenocarcinoma (endocrine, metastases)

• Patients with confirmed pancreatic ductal adenocarcinoma classified as locally advanced pancreatic adenocarcinoma (LPAC)
• Patients with no evidence of peritoneal or hematogenous metastasis
• 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
• Measurable tumor according RECIST criteria v 1.1
• Low tumor burden with at least one lesion equal/less than 3,5 cm that is suitable for US guided injection (and needle biopsy).
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Patients must be eligible for chemotherapy treatment (based on standard of care)
• Patient older than 18 years of age
• Adequate hepatic and kidney function/Safe hematologic profile
• Negative serum pregnancy test for females of childbearing potential within days of starting treatment
• Willingness and ability to comply with the scheduled visits, treatment plan, imaging procedures, laboratory tests and other study procedures, including lipoaspirate collection (liposuction)