A First-in-human Clinical Evaluation of SN132D in Patients With Breast and Pancreatic Cancer (SPAGOPIX-01)

A First-in-human Clinical Evaluation of the Novel Intravenous Contrast Agent SN132D in Patients With Breast and Pancreatic Cancer

This phase I, first-in-human (FIH) study is open-label, non-randomised and non-placebo-controlled. The study is designed to evaluate the safety, tolerability and pharmacokinetics (PK) of a single intravenous dose of SN132D in approximately 24 patients with breast and pancreatic cancer. Magnetic resonance imaging (MRI) will be performed pre- and post-infusion of SN132D.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Pancreas Cancer
• Intervention / Treatment: Drug: SN132D

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, SE-41345
    • Gothia Forum Clinical Trial Center
  • Uppsala, Sweden, SE-75185
    • CTC Clinical Trial Consultants AB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent including willingness to undertake 3 MRI investigations (30 minute each) in one day
2. Histological or cytological diagnosis of breast cancer > 5 mm (cT1c-cT4; cN0-cN3; Mx) or known or suspected pancreatic cancer with hepatic involvement with available or scheduled gadolinium enhanced MRI of the pancreas
3. At least 3 weeks between core needle biopsy and planned pre-dose MRI. Fine needle aspiration is allowed at any time before MRI.
4. Female and at least 18 years of age when signing the informed consent.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 at screening

6. Adequate renal and hepatic function: estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73 m2 (determined by the revised Lund-Malmö GFR estimating equation), bilirubin <1 x upper limit of normal (ULN; (in subjects with liver metastases <5 x ULN)), creatinine <1 x ULN, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) < 1 x ULN.

   Bilirubin ULN: 25 µmol/L, creatinine ULN: 90 µmol/L, ASAT ULN: 0.60 µkat/L and ALAT ULN: 0.75 µkat/L) at the screening visit.

7. Females of child-bearing potential* must agree to the use of effective contraception** or practice abstinence during the study and for 30 days after the IMP administration.

8. Adequate haematological function: haemoglobin ≥90 g/L, absolute neutrophil count (ANC) ≥1.3x109 /L and platelet count ≥ 100 x 109 /L.

   • A female of child-bearing potential is a sexually mature female who 1) has not undergone a hysterectomy or bilateral oophorectomy, or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e. had had menses at any time in the preceding 24 consecutive months).

     • Effective contraception is defined as contraceptive methods with a failure rate of < 1% to prevent pregnancy (combined [oestrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD]or intrauterine hormone-releasing system [IUS]).

Exclusion Criteria:

1. Female patients who are pregnant or who are currently breast feeding.
2. Conditions contraindicating MRI including, but not limited to, body mass index (BMI) > 40 kg/m2 at screening claustrophobia, metallic implants or internal electrical devices (e.g., cochlear implant, nerve stimulator, gastric pacemaker, bladder stimulator, pacemaker, defibrillator, artificial valves in heart, aneurysm clips, etc.), and permanent makeup or tattoos which in the Investigator's opinion might jeopardise the patient's safety or interfere with the imaging measurements. The Investigator is encouraged to contact the MR clinic for advice on which implants, tattoos, etc may be unsuitable.
3. Other malignancy than breast and pancreatic cancer within the past 5 years with the exception of in situ removal of basal cell carcinoma or resected benign colonic polyps.
4. Moderate to severe hypertension as judged by the Investigator.
5. History of significant cardiovascular disease such as myocardial infarction, congestive heart failure, stroke, serious cardiac arrhythmias. History of angina within 6 months prior to screening.
6. Clinically diagnosed obstruction of bile duct as judged by investigator.
7. Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting electrocardiogram (ECG) at the time of screening, as judged by the Investigator.
8. Abnormalities detected during examination at screening and admission, which in the opinion of the Investigator, may either put the patient at risk because of participation in the study or influence the results or the patient's ability to participate in the study.
9. Active infection requiring systemic treatment within one week prior to agent administration.
10. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study.
11. Seropositive for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibodies.
12. Any use of alcohol within 24 hours of admission to the clinic.
13. Plasma donation within 1 month of screening or any blood donation or corresponding blood loss during 3 months prior to screening.
14. Use of investigational agent within four weeks before Visit 1 or plans to initiate treatment with an investigational agent during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose (i.v.) SN132D	Drug: SN132D; Novel manganese-based macromolecular MRI contrast agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment related adverse events (AEs)	Frequency, severity and seriousness of AEs including clinically significant changes in physical examinations, safety laboratory parameters, vital signs, electrocardiograms and injection site reactions will be assessed.	Baseline up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary efficacy (MRI enhancing effect)	Preliminary efficacy will be evaluated by assessing changes between pre-dose images and post-dose images acquired using T1-weighted imaging sequences, analysing contrast-to-noise in primary tumour vs reference tissue, signal-to-noise in primary tumour, contrast-to-noise in liver and pancreas vs reference tissue and signal-to-noise in liver and pancreas. Additionally, Changes between pre-dose T1 and post-dose T1 in liver and pancreas will be analysed. In pancreatic cancer patients, presence or absence of liver metastases and a number of lesions and diameter of smallest and largest lesion in liver will also be analysed.	Day 1
Pharmacokinetics as measured by area under the plasma concentration-time curve from time 0 to the last measurable time point (AUC0-t) for manganese (Mn) (mM x min)	Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.	Baseline up to Day 2
Pharmacokinetics as measured by area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUCinf) for Mn (mM x min)	Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.	Baseline up to Day 2
Pharmacokinetics as measured by maximum plasma concentration (Cmax) for Mn (µg Mn/mL)	Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.	Baseline up to Day 2
Pharmacokinetics as measured by time to Cmax (Tmax) for Mn (h)	Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.	Baseline up to Day 2
Pharmacokinetics as measured by plasma elimination half-life (T½) for Mn (h)	Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.	Baseline up to Day 2
Pharmacokinetics as measured by total body clearance (CL) for Mn (L/h)	Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.	Baseline up to Day 2
Pharmacokinetics as measured by apparent volume of distribution at steady state (Vss) for Mn (L) the terminal phase half-life (T½) for manganese (Mn)	Samples for pharmacokinetic analysis will be collected at predose and at 10 min, 20 min, 60 min, 65 min, 75 min, 90 min, 105 min, 3 h and 9 h post start of dosing.	Baseline up to Day 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI enhancement of selected axillary (breast cancer patients) or regional and distant (e.g paraaortic lymph nodes, pancreatic cancer patients) lymph nodes	MRI enhancement of selected lymph nodes will be assessed by changes in contrast-to-noise vs reference tissue and signal-to-noise in selected lymph nodes between pre-dose images and 2 post-dose occasions	Day 1
Visualization of the pancreatic duct	Visualization of the pancreatic duct will be assessed by a certified radiologist	Day 1

Collaborators and Investigators

• Sponsor: Spago Nanomedical AB
• Collaborators: CTC Clinical Trial Consultants AB; Antaros Medical
• Investigators: Principal Investigator: Folke Sjöberg, MD, Prof, CTC Clinical Trial Consultants AB; Principal Investigator: Dan Curiac, MD, PhD, Gothia Forum Clinical Trial Center

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2019
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: August 27, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: SN132D CSP final version 6.0; 2018-002193-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No