Pancreatic Cancer
Conditions
Keywords
pancreatic cancer, MUC5AC
Brief summary
This trial will be a non-randomized, Phase I trial to evaluate safety, tolerability, biodistribution, radiation dosimetry, pharmacokinetics and PET imaging properties following an infusion of 37 MBq (1 mCi) of 89Zr-labeled hNd2\* (NMK89) in patients with pancreatic cancer that are positive for MUC5AC. Image acquisition is conducted using a PET/CT machine. \* hNd2: Recombinant humanized Nd2 (anti-human MUC5AC monoclonal antibody)
Interventions
DRUGNMK89
Route of administration: intravenous infusion
Sponsors
Nihon Medi-Physics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide informed consent. 2. Male or female ≥ 18 years of age. 3. Histologically confirmed diagnosis of pancreatic adenocarcinoma. 4. Willing to provide biopsy specimens for purposes of confirmation of MUC5AC expression. 5. Confirmed MUC5AC expression at pre-screening. 6. Measurable disease. 7. Female patients of child-bearing potential must have a negative serum pregnancy test within 30 days prior to infusion of NMK89. 8. Willing to comply with the study protocol requirements. 9. Willing to provide a tumor resection specimen or biopsy specimen, if the patient undergoes tumor resection or biopsy between Day 16 and Day 60.
Exclusion criteria
1. Known hypersensitivity to the investigational medicinal product (IMP) or any of the excipients. 2. History of another primary cancer within the 2 years prior to enrollment, except for the curatively treated in situ cancers. 3. Exposure to any investigational treatments within 30 days prior to the planned date of infusion of NMK89. 4. Ongoing toxicity ≥ Grade 2. 5. Pleural effusion or peritoneal fluid ≥ Grade 3. 6. Active hepatitis B, hepatitis C, HIV, or other progressing infectious disease. 7. Uncontrolled diabetes. 8. Autoimmune disease or idiopathic thrombocytopenic purpura. 9. Exposure to any radiopharmaceuticals. 10. Planned antineoplastic therapies on the planned date of NMK89 infusion. 11. Use of bevacizumab or any other anti-angiogenic agent. 12. Uncontrolled intercurrent illness. 13. ECOG PS: ≥ 2. 14. Participants do not have adequate organ and marrow function. 15. Female patients that are pregnant or breast-feeding. 16. Positive urine screen for illegal drugs, or abuse of prescribed drugs at Screening. 17. Participants with contraindications to contrast agent injection used for diagnostic CT. 18. Deemed inappropriate to participate by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of a single infusion of NMK89: Frequency and severity of abnormal ECOG PS (Eastern Cooperative Oncology Group Performance Status) | Screening to Day 8 | — |
| Safety and tolerability of a single infusion of NMK89: vital sign 2 | Screening to Day 8 | Heart rate |
| Safety and tolerability of a single infusion of NMK89: vital sign 3 | Screening to Day 8 | Systolic blood pressure (SBP) |
| Safety and tolerability of a single infusion of NMK89: vital sign 4 | Screening to Day 8 | Diastolic blood pressure (DBP) |
| Safety and tolerability of a single infusion of NMK89: 12-lead ECG (Electrocardiogram) 1 | Screening to Day 8 | PR interval |
| Safety and tolerability of a single infusion of NMK89: 12-lead ECG 2 | Screening to Day 8 | RR interval |
| Safety and tolerability of a single infusion of NMK89: 12-lead ECG 3 | Screening to Day 8 | QRS interval |
| Safety and tolerability of a single infusion of NMK89: 12-lead ECG 4 | Screening to Day 8 | QT |
| Safety and tolerability of a single infusion of NMK89: 12-lead ECG 5 | Screening to Day 8 | Corrected QT |
| Safety and tolerability of a single infusion of NMK89: Frequency and severity of abnormal adverse events (AEs) (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v 5.0)) | Baseline up to Day 60 | — |
| Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - hematology | Screening to Day 8 | Hematology included hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell count (total and differential: leukocytes, neutrophils, eosinophils, basophils, lymphocytes, monocytes), red blood cells, platelets. |
| Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - serum chemistry | Screening to Day 8 | Serum chemistry included sodium, potassium, chloride, calcium, glucose, creatinine, urea or BUN, albumin, total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, gamma-glutamyl transferase (GGT), lipase, amylase and total protein. |
| Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - clotting factors | Screening to Day 8 | Clotting factors included prothrombin time (quick), reagent-independent prothrombin ratio (international normalized ratio; INR), activated partial thromboplastin time (aPTT). |
| Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - urinalysis | Screening to Day 8 | Urinalysis included specific gravity, pH, protein, glucose, blood, leukocytes, ketones, nitrite, albumin, creatinine. |
| Safety and tolerability of a single infusion of NMK89: physical examination 2 | Screening | Height |
| Safety and tolerability of a single infusion of NMK89: vital sign 1 | Screening to Day 8 | Body temperature |
| Safety and tolerability of a single infusion of NMK89: physical examination 1 | Screening to Day 8 | Body weight |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biodistribution: Time-integrated activity coefficients (TIACs) (hr) | Day 1 to Day 8 | PET/CT image acquisitions will be obtained to assess biodistribution of NMK89 in normal tissues and tumors in patients. |
| Radiation Dosimetry of NMK89: Normalized radiation absorbed doses and normalized effective dose | Day 1 to Day 8 | Whole-body radiation dosimetry of NMK89 in patients will be estimated. |
| Optimization of positron emission tomography (PET) Scan Protocol: Optimal time from injection to start of PET | Day 1 to Day 8 | Optimal time from injection to start of PET acquisition will be determined. |
| Predictive radiation dosimetry of hNd2 labeled with therapeutic radionuclide: Normalized absorbed doses and normalized effective dose | Day 1 to Day 8 | Whole-body radiation dosimetry (if hNd2 will be labeled with a therapeutic radionuclide) will be estimated. |
| Blood Pharmacokinetics (PK): Concentration of total antibody in blood | Pre-infusion (baseline) to Day 8 | PK will be evaluated based on concentration of total antibody obtained within defined volumes of blood. |
| Blood Pharmacokinetics (PK): Concentration of total radioactive counts in blood | Day 1 to Day 8 | PK will be evaluated based on concentration of total radioactive counts obtained within defined volumes of blood. |
| Blood Pharmacokinetics (PK): Abundance ratio of unmetabolized 89Zr-labeled hNd2(%) | Day 1 to Day 8 | To calculate this ratio, the count of metabolites and non-metabolic components is obtained |
| Urine Pharmacokinetics (PK): Concentration of total antibody in urine | Pre-infusion (baseline) to Day 8 | PK will be evaluated based on concentration of total antibody obtained within defined volumes of urine. |
| Urine Pharmacokinetics (PK): Concentration of total radioactive counts in urine | Day 1 to Day 8 | PK will be evaluated based on concentration of total radioactive counts obtained within defined volumes of urine. |
| Urine Pharmacokinetics (PK): Radioactivity counts of 89Zr-labeled hNd2 and metabolites components | Day 1 to Day 8 | Radioactivity counts of 89Zr-labeled hNd2 and metabolites components are measured by magnetic separation, and the abundance ratio of unmetabolized 89Zr-labeled hNd2 (%) will be calculated. |
| Biological half-life of the radionuclide (hr) | Day 1 to Day 8 | Biological half-life of the radionuclide (hr) will also be estimated. |
| Public Safety: Radiation measurement | Day 1 | Public safety will be assessed by acquiring dosimeter readings of a patient following infusion. |
| Biodistribution: Fractional injected 89Zr radioactivity values (percentage of injected dose(%ID)) | Day 1 to Day 8 | PET/CT image acquisitions will be obtained to assess biodistribution of NMK89 in normal tissues and tumors in patients. |
Countries
United States
Outcome results
None listed