None listed
Conditions
Brief summary
The purpose of this study is to evaluate how a drug moves around the body. The drug is called C595 Mab and will be combined with some existing radioactive chemicals routinely used in cancer imaging, called 99mTc and 111In. Who is it for? You may be eligible for this study if you are aged 18 or older with locally advanced or metastasised pancreatic cancer. Study details All participants in this study will have their scheduled biopsy. After laboratory testing confirms eligibility, participants will receive an injection of C595 Mab with 99mTc through a needle in the arm. Participants will then have a one CT scan. Depending on the results, after two weeks new participants will have an injection of C595 Mab with 111In through a needle in the arm, and three CT scans. Participants that will receive either 99mTc or 111In injections will have their vital signs (like temperature, blood pressure, heart rate and pulse) monitored for a few hours after their injection. It is hoped this research will help provide further information on the safety and usefulness of C595 as part of a potential future therapy for pancreatic cancer.
Interventions
20 patients with either locally advanced or metastasized Pancreatic Ductal Adenocarcinoma (PDAC), who are referred for Endoscopic Ultrasound (EUS) Fine Needle Acquisition (FNA), will be approached for the study. Staging will include CT scans of the chest, abdomen and pelvis, and a diagnostic 18FDG PET scan. Based on the probable 80% positive rate for the glycoprotein Mucin-1 (MUC-1), it is expected that 15-16 patients who have MUC-1 positive PDAC will be recruited for the study.
In addition to
20 patients with either locally advanced or metastasized Pancreatic Ductal Adenocarcinoma (PDAC), who are referred for Endoscopic Ultrasound (EUS) Fine Needle Acquisition (FNA), will be approached for the study. Staging will include CT scans of the chest, abdomen and pelvis, and a diagnostic 18FDG PET scan. Based on the probable 80% positive rate for the glycoprotein Mucin-1 (MUC-1), it is expected that 15-16 patients who have MUC-1 positive PDAC will be recruited for the study. In addition to histological evaluation of the EUS-guided biopsy, MUC-1 receptor staining using Immunohistochemistry techniques will be done at the Department of Pathology, Royal Adelaide Hospital (RAH). Only patients who have confirmed PDAC with positive MUC-1 stain will be recruited to the next study phase. In all patients, full blood count, kidney and liver function, and urinary dipstick for proteinuria/hematuria tests will be performed, including staging. The first 10 recruited patients will undergo immediate bio-distribution evaluation with 99mTc-C595 conjugates planar and SPECT/CT scanning, within 2 weeks after the biopsy. This is to ensure that the study will not cause any unnecessary delay to chemotherapy. On the study day, the patient will be evaluated with one planar and SPECT/CT scan, up to 4 hours after an IV injection of 99mTc-C595 conjugate, prepared by the Department of Nuclear Medicine, RAH. For 111 MBq of 99mTc-C595, the dose is ~1.2 mSv. Over the 4 hours, vital signs (temperature, blood pressure, heart rate and pulse) will be taken every 15 minutes. Providing the vital signs are normal, the patients will be discharged home after the SPECT/CT scan. Providing that the 99mTc-C595 conjugate distribution demonstrates specific localization of C595 Mab to the primary and secondary lesions of pancreatic cancer, the subsequent recruited patients (n= 5 or 6 subjects) will be evaluated with 111In-C595 injection to ensure that there are no delayed anomalous organ uptake, and confirm ongoing binding to the pancreatic cancer lesion(s). For 80 MBq of 111In-C595, the dose is ~18 mSv. In these studies, the patients will undergo one SPECT/CT scan at 4 hours, one at 24 hours, and one up to Day 4 after IV injection of 111In-C595. Again, vital signs (temperature, blood pressure, heart rate and pulse) will be taken every 15 minutes over the first 3 hours of injection. If the 99mTc-C595 conjugate distribution study fails to demonstrate specific localization of C595 Mab, the study will be terminated at this point. Both 99mTc-C595 and 111In-C595 are considered interventions for the study. This is a proof-of-concept study to evaluate the specific bio-distribution of the two C595 labelled radionuclide markers (99mTc and 111In immunoconjugates) to pancreatic cancer cells in patients who have advanced MUC1-positive pancreatic carcinoma. In111 and Tc99m-C595 conjugates will be manufactured at the RAH Nuclear Medicine Department Radiopharmacy Hot Laboratory. All manufacturing processes will be undertaken in a lead lined Clas II biological safety cabinet in the laboratory. Production will be undertaken by a radio-chemist/pharmacist. Both injections will be administered by the investigator of the study.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Non-randomised trial
Primary purpose
Diagnosis
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(i) Subjects aged 18 years or older, and able to provide informed consent and expected to survive for >3 months. (ii) Histological proven pancreatic ductal carcinoma with positive MUC-1. (iii) Karnofsky performance status > 70%. (iv) Neutrophil count > f 1.5 x 10^9/L, platelet counts of greather than/equal to 100 x 10^9/L; Hb greater than/equal to 9.0g/dL (90 g/L) without transfusion or erythropoietin support within 2 weeks prior to screening, total bilirubin level less than/equal to 1.5 x ULN, AST and ALT levels more than 2 times the upper limit of normal and GFR greater than/equal to 60 mL/min.
Exclusion criteria
(i) Known renal conditions: glomerulonephritis; IgA nephropathy, acute renal failure, current CNS metastases. (ii) Known mouse product allergy. (iii) Chemo or immunotherapy within 4 weeks prior or radiotherapy within 2 weeks of Target Radio-Immunotherapy. (iv) Liver disease with liver enzyme greater than 3 times of normal. (v) Pregnancy or lactation.
Outcome results
None listed