Alpha Radiation Emitters (DaRT) With Chemotherapy for the Treatment of Locally Advanced and Metastatic Pancreatic Cancer

Inclusion criteria

• Histologically and/or cytologically proven newly diagnosed locally advanced inoperable pancreatic adenocarcinoma (Cohort 1) OR histologically and/or cytologically proven newly diagnosed metastatic pancreatic adenocarcinoma (Cohort 2).
• Patients will start treatment with mFOLFIRINOX (up to 4 cycles) before DaRT insertion
• Target lesion is technically amenable for Alpha DaRT sources implantation.
• Measurable lesion per RECIST (version 1.1) criteria
• Lesion size ≤ 5 cm in the longest diameter
• Interstitial radiation indication validated by a multidisciplinary team.
• ECOG Performance Status Scale 0 -2
• Life expectancy is more than 6 months
• WBC ≥ 3500/μl, granulocyte ≥ 1500/μl
• Platelet count ≥60,000/μl
• Creatinine ≤1.9 mg/dL
• AST and ALT ≤ 2.5 X upper limit of normal (ULN)
• INR \< 1.4 for patients not on Warfarin
• Age ≥18 years old
• Subjects are willing and able to sign an informed consent form
• Women of childbearing potential (WOCBP) will have evidence of negative pregnancy test before the Ra-224 implantation and are required to use an acceptable contraceptive method to prevent pregnancy for 3 months after initiation of Alpha DaRT therapy.
• Patients must agree to use adequate contraception (vasectomy or barrier method of birth control) prior to study entry, for the duration of study participation and for 3 months after DaRT insertion.

Exclusion criteria

• For Cohort 1 only: Borderline unresectable pancreatic cancer, and/or fit for surgical exploration unless patient refuses surgery.
• For Cohort 1 and Cohort 2: Prior treatment for pancreatic cancer, including chemotherapy except for 1 - 4 cycles of mFOLFIRINOX, radiation therapy, immunotherapy, etc.
• Known hypersensitivity to any of the components of the treatment.
• Patients undergoing systemic immunosuppressive therapy excepting intermittent, brief use of systemic corticosteroids.
• Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months.
• Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial or interfere with the study endpoints.
• Has a known additional malignancy that is progressing or requires active treatment.
• Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, low risk prostate cancer, or in situ cervical cancer.
• Patient requires treatment not specified in this protocol which may conflict with the endpoints of this study including evaluation of response or toxicity of DaRT.
• Patients do not agree to use adequate contraception (vasectomy or barrier method of birth control) prior to study entry, for the duration of study participation and for 3 months after DaRT insertion.
• Volunteers participating in another interventional study in the past 30 days which might conflict with the endpoints of this study or the evaluation of response or toxicity of DaRT.
• High probability of protocol non-compliance (in opinion of investigator).
• Breastfeeding women or women of childbearing potential unwilling or unable to use an acceptable contraceptive method to prevent pregnancy for 3 months after DaRT insertion
• Patients who are at high risk of complications from radiation due to genetic conditions/mutations, inflammatory bowel disease, or connective tissue disease.