Locally advanced pancreatic adenocarcinoma MedDRA version: 20.0 Level: PT Classification code 10073364 Term: Ductal adenocarcinoma of pancreas System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Cellule Umane Autologhe Adipose Stromali Perivascolari Geneticamente Modificate per la Secrezione di
Product Code: [RR001]
Pharmaceutical Form: Suspension for injection
Current Sponsor c
Sponsors
RIGENERAND Srl
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a) Patients with histologically and/or cytologically confirmed pancreatic ductal adenocarcinoma b) Patients with no evidence of peritoneal or hematogenous metastasis c) 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. d) Measurable tumor according RECIST criteria v 1.1 e) Low tumor burden with at least one lesion equal/less than 3,5 cm that is suitable for US guided injection (and needle biopsy). f) Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. g) Patients must be eligible for standard of care treatment with GEM/Nab-PTX h) Patient older than 18 years of age i) Evidence of a personally signed and dated Ethical Committee-approved Informed consent form indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study j) Adequate hepatic function, with bilirubin 30 mL/min l) Absolute neutrophil count (ANC) =1.0 x 109/l, hemoglobin =9 g/dl, platelet count = 100 x 109/l, prothrombin (INR) =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: a) Female patients with childbearing age or pregnancy or breast feeding. Female patients shall agree to use effective contraception or be surgically sterile or postmenopausal. b) Patient with pancreatic cystic tumor or pancreatic pseudocyst c) Patient with pancreatic tumor different from adenocarcinoma (endocrine, metastases) d) Patients with unknown stage or recurrent pancreatic cancer e) Patients with immunosuppression or susceptibility to viral infection f) Patients with HIV, hepatitis B, hepatitis C, HTLV-I/II, Treponema Pallidum infections g) Patients with liver cirrhosis or other documented liver diseases h) Patient contraindication to gemcitabine + nab-paclitaxel treatments i) Patients with not approachable US window for intratumoral injection of RR001 as evaluated by US examination of the abdomen j) Documented allergy to fluoroquinolones k) Previous of radiotherapy and chemotherapy for PDAC l) Previous haematopoietic stem cell or organ transplantation m) Irreversible cardiac arrhythmias requiring permanent medication n) Heart insufficiency (> grade II, New York Heart Association NYHA criteria) o) History within the last year of acute or subacute coronary cyndromes including myocardial infarction, unstable or severe stable angina pectoris p) Uncontrolled hypertension q) Patient not efficiently treated for jaundice (biliary stent or bypass) if present at time of diagnosis r) 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). s) Moderate to large volume ascites t) Active autoimmune disease u) Use of any investigational agents within 21 days from the administration of study treatment v) Patient has had major open surgery within the 3 months prior to the administration of study treatment w) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety, feasibility of intra-tumoral injection of the RR001 administered by ultrasound (US) guided injections in combination with standard of care therapy based on GEM/Nab-PTX and to establish the maximal tolerated dose (MTD) and recommended phase IIb dose (RP2D) of intratumoral injections of RR001 after three dose levels delivery in combination with standard of chemotherapy;Secondary Objective: 1. Antitumor activity and response rate by RECIST 1.1 criteria 2. Percentage of patients successfully undergoing to surgery and percentage of pathological resection (R0 vs. R1 vs. R2) 3. Time to disease progression, progression free survival (PFS) and overall survival (OS) 4. Quality of life (EORTC QLQ-C30, QLQ-PAN26) 5. Exploratory endpoints (sTRAIL levels in serum and urine by ELISA, detection of sTRAIL encoding transgene in blood, urine and tumor biopsies by qPCR, histology on tumor biopsies, DPC4/SMAD4 status, radiological objectives);Primary end point(s): Co-primary endpoints will be feasibility and safety. Feasibility will be expressed as number of eligible patients receiving the gene therapy within 35 days from the liposuction. The intervention will be defined feasible if at least 80% of enrolled patients will be treated. Tolerability and safety will be expressed as number of patients recruited/treated experiencing any dose-limiting toxicity (DLT), adverse event (AE), adverse reaction (AR), unexpected adverse reaction (UAR), severe adverse event (SAE), suspected unexpected serious adverse reaction (SUSAR), or adverse event of special interest (AESI).;Timepoint(s) of evaluation of this end point: Feasibility will be evaluated for each patient between 46-57 days from enrollment and overall feasibility (at least 80% of patients treated with RR001) will be assessed at the end of study. Number and type of dose-limiting toxicities will be assessed at day +21 from RR001 injection for each patient. Safety endpoints related to RR001 will be ev | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes in EORTC quality of life scores; Frequency and proportion of patients eligible for the surgery among those receiving the RR001 infusion; Changes in tumor markers (Ca 19.9, CEA); Frequency and proportion of patients not eligible for the surgery but reporting stable disease among those receiving the RR001 infusion; Mortality rate; Tumor response rate (RECIST criteria);Timepoint(s) of evaluation of this end point: From baseline to end of study; Visit 18 (after 21 days from RR001 administration); From baseline to end of study; Visit 22 (after 90 days from RR001 administration); 2, 4, 12 weeks after the RR001 infusion; From baseline to end-of-study | — |
Countries
Italy
Contacts
Public ContactRegulatory Affairs
RIGENERAND srl
Outcome results
None listed