RR001, a cell-based gene therapy administered in combination with chemotherapy for the treatment of patients with locally advanced pancreatic cancer. Phase I /IIa clinical trial (open label and non-randomized) to test the effects (safety & efficacy) of increasing doses of RR001.
- Conditions
- Locally advanced, non-resectable pancreatic adenocarcinomaDuctal adenocarcinoma of pancreas
- Registration Number
- 2024-516019-26-00
- Lead Sponsor
- Eir Biotherapies S.r.l.
- Brief Summary
1. 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
2. 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 18
Patients with histologically and/or cytologically confirmed pancreatic ductal adenocarcinoma
Adequate hepatic function, with bilirubin < 1.5 x the ULN, and AST and ALT < 2.5 x ULN
Adequate kidney function with serum creatinine <2 x the ULN or creatinine clearance >30 mL/min
Absolute neutrophil count (ANC) ≥1.0 x 10e9/l, hemoglobin ≥9 g/dl, platelet count ≥ 100 x 10e9/l, prothrombin (INR) <1.5
Life expectancy of at least 12 weeks
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
Patients with no evidence of peritoneal or hematogenous metastasis
Patients classified as non-resectable 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 standard of care treatment with GEM/Nab-PTX
Patient older than 18 years of age
Evidence of a personally signed and dated Ethics Committee-approved Informed consent form indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study
Female patients with childbearing age or pregnancy or breast feeding. Female patients shall agree to use effective contraception or be surgically sterile or postmenopausal
Previous of radiotherapy and chemotherapy for PDAC
Previous haematopoietic stem cell or organ transplantation
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 cyndromes including myocardial infarction, unstable or severe stable angina pectoris
Uncontrolled hypertension
Patient not efficiently treated for jaundice (biliary stent or bypass) if present at time of diagnosis
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)
Moderate to large volume ascites
Active autoimmune disease
Patient with pancreatic cystic tumor or pancreatic pseudocyst
Use of any investigational agents within 21 days from the administration of study treatment
Patient has had major open surgery within the 3 months prior to the administration of study treatment
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
Patient with pancreatic tumor different from adenocarcinoma (endocrine, metastases)
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
Patient contraindication to gemcitabine +nab-paclitaxel treatments
Patients with not approachable US window for intratumoral injection of RR001 as evaluated by US examination of the abdomen
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To investigate the safety, 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 To investigate the safety, 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
To establish the MTD and RP2D of intratumoral injections of RR001 after three dose levels delivery in combination with standard of care therapy To establish the MTD and RP2D of intratumoral injections of RR001 after three dose levels delivery in combination with standard of care therapy
- Secondary Outcome Measures
Name Time Method Quality of life by scoring of quality of life according to the EORTC QLQ-C30 and QLQ-PAN26 Quality of life by scoring of quality of life according to the EORTC QLQ-C30 and QLQ-PAN26
Target tumor response: antitumor activity will be assessed by objective radiologic assessment using RECIST 1.1 criteria Target tumor response: antitumor activity will be assessed by objective radiologic assessment using RECIST 1.1 criteria
Response rate: the overall rates for objective response (complete, partial responses, stable disease, progressive disease) will be assessed by objective radiographic assessment using RECIST 1.1 criteria Response rate: the overall rates for objective response (complete, partial responses, stable disease, progressive disease) will be assessed by objective radiographic assessment using RECIST 1.1 criteria
Percentage of patients successfully undergoing to surgery and percentage of pathological resection (R0 vs. R1 vs. R2) Percentage of patients successfully undergoing to surgery and percentage of pathological resection (R0 vs. R1 vs. R2)
Time to disease progression Time to disease progression
Progression free survival (PFS) Progression free survival (PFS)
Overall survival (OS) Overall survival (OS)
Tumor markers in serum (CEA, CA19.9 if present at the diagnosis) Tumor markers in serum (CEA, CA19.9 if present at the diagnosis)
Trial Locations
- Locations (1)
Azienda Ospedaliero Universitaria Di Modena
🇮🇹Modena, Italy
Azienda Ospedaliero Universitaria Di Modena🇮🇹Modena, ItalyAnnalisa FontanaSite contact390594223308fontana.annalisa@aou.mo.it