A Feasibility and Safety Study of Intratumoral Diffusing Alpha Radiation Emitters for the Treatment of Advanced Pancreatic Cancer

Inclusion Criteria

• Histologically and/or cytologically proven locally advanced or metastatic pancreaticadenocarcinoma

• Patients must have i) received at least one line of chemotherapy OR ii) aremedically unfit for further chemotherapy, AND iii) the tumor is still not deemed asresectable with radical surgery or the patient does not wish to go through surgery

• Target lesion is technically amenable for at least 50% coverage by the Alpha DaRTseeds as determined by the treating physician

• Interstitial radiation indication validated by a multidisciplinary team

• Measurable lesion per RECIST (version 1.1) criteria

• Lesion size ≤ 5 cm in the longest diameter

• Age ≥18 years old

• ECOG Performance Status Scale ≤ 2

• Life expectancy is more than 6 months

• WBC ≥ 3500/µl, granulocyte ≥ 1500/µl

• Platelet count ≥60,000/µl

• Calculated or measured creatinine clearance ≥ 60cc/min. Calculated or measuredcreatinine clearance can be≥ 40cc/min given stability of creatinine levels over thepast three weeks (at least 1 test per week).

• AST and ALT ≤ 2.5 X upper limit of normal (ULN)

• INR < 1.4 for patients not on Warfarin

• Subjects are willing and able to sign an informed consent form

• Women of childbearing potential (WOCBP) will have evidence of negative pregnancytest before the Ra-224 implantation and are required to use an acceptablecontraceptive method to prevent pregnancy for 3 months after brachytherapy.

• Patients must agree to use adequate contraception (vasectomy or barrier method ofbirth control) prior to study entry, for the duration of study participation and for 3 months after discontinuing therapy.

Exclusion Criteria:

• Concomitant chemotherapy or immunotherapy within the past 4 weeks

• Brain metastases

• Borderline unresectable pancreatic cancer, and/or cases fit for surgical explorationunless patient refuses surgery

• Known hypersensitivity to any of the components of the treatment.

• Patients undergoing systemic immunosuppressive therapy excepting intermittent, briefuse of systemic corticosteroids.

• Clinically significant cardiovascular disease, e.g. cardiac failure of New YorkHeart Association classes III-IV, uncontrolled coronary artery disease,cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history ofmyocardial infarction in the last 12 months.

• Patients with uncontrolled intercurrent illnesses including, but not limited to anactive infection requiring systemic therapy or a known psychiatric or substanceabuse disorder(s) that would interfere with cooperation with the requirements of thetrial 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 ofthe skin that has undergone potentially curative therapy or in situ cervical cancer.

• Patient requires treatment not specified in this protocol which may conflict withthe endpoints of this study including evaluation of response or toxicity of DaRT.

• Patients do not agree to use adequate contraception (vasectomy or barrier method ofbirth control) prior to study entry, for the duration of study participation and for 3 months after discontinuing therapy.

• Volunteers participating in another interventional study in the past 30 days whichmight conflict with the endpoints of this study or the evaluation of response ortoxicity of DaRT.

• High probability of protocol non-compliance (in opinion of investigator).

• Breastfeeding women or women of childbearing potential unwilling or unable to use anacceptable contraceptive method to prevent pregnancy for 3 months after RT.