liver nodules of less or equal to 3 cm suspected for HCC in subjects with chronic liver disease MedDRA version: 19.0 Level: PT Classification code 10019695 Term: Hepatic neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: G03277.066
Pharmaceutical Form: Solution for injection
CAS Number: 933983-75-6
Other descriptive name: P03277
Concentration unit: mol/l mole(s)/litre
Concentration type: equal
Concentrat
Sponsors
GUERBET
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Female or male adult subject aged at least 18 years old or older (subject having reached legal majority age). 2.Subject able and willing to participate to the study. 3.Subject having read the information and having provided his/her consent to participate in writing by dating and signing the informed consent prior to any study related procedure being conducted. 4.Subject presenting with liver cirrhosis or chronic liver diseases as shown by previous liver biopsy or by combination of clinical, endoscopic, biological, ultrasound parameters, and elastography 5.Subject presenting with one to a maximum of 3 untreated hepatic nodule(s) of less than or equal to 3 cm (long axis) previously identified and/or characterized through enhanced CT and/or MRI within a maximum of 21 days before P03277 imaging, confirmed for HCC or not 6.Female subject must have effective contraception (hormonal contraception or intra-uterine device) or be surgically sterilized or post-menopausal (>2 years amenorrhea) 7.Subject affiliated to national health insurance according to local regulatory requirement Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1.Pregnant or breast-feeding female subject (a female subject of childbearing potential or with amenorrhea for less than 12 months must have a negative urine or serum pregnancy test at screening and within 24 hours prior to study MRI and must be using a medically approved contraception method*). *medically approved contraception methods include: female sterilization, barrier methods of contraception (condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository), use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception, placement of an Intrauterine Device (IUD) or Intrauterine System (IUS). 2.Subject presenting with hepatic nodule more than 3 cm in addition to nodule(s) less than or equal to 3 cm 3.Subject already treated for HCC by surgery or thermal ablation for which the resection or coagulation area is less than 2cm from the new nodule(s) 4.Subject previously treated by transarterial chemoembolization 5.Subject with moderate or severe renal impairment (eGFR < 60 mL/min/1.73m2) based on measurement done or available within the 7 days before P03277 administration and assessed after any iodinated contrast agent administration, or with dialysis end stage renal disease (ESRD) 6.Subject with known class III/IV congestive heart failure according to the New York Heart Association classification 7.Subject having received or is scheduled to receive any contrast agent within 7 days before P03277 planned administration date and within 3 days after P03277 planned administration date. 8.Subject with known contra-indication(s) to the use or with known sensitivity to one of the products under investigation or to drugs from a similar pharmaceutical class as P03277 9.Subject having received any investigational medicinal product within 7 days prior to P03277 planned administration date 10.Subject presenting with any contraindication to MRI examination (see recommendations of the French Society of Radiology) 11.Subject having planned palliative/treatment interventions for the suspected nodules (radiotherapy, chemotherapy or others) during the study period except for biopsy/surgery 12.Subject related to the investigator or any other study staff or relative directly involved in the study conduct 13.Subject previously enrolled in this study 14.Subject with anticipated, current or past condition (medical, psychological, social or geographical) that would compromise the subject’s safety or her/his ability to participate in the study. 15.Subject unlikely to comply with the protocol (e.g., uncooperative attitude, inability to return for follow-up visits and/or unlikelihood of completing the study).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the diagnostic value for hepatocellular carcinoma (HCC) of P03277 in patients with suspected small nodules and chronic liver disease.;Secondary Objective: To evaluate multiple quantitative and qualitative efficacy parameters and the safety (clinical and biological) profile of P03277 following single administration in suspected HCC patients;Primary end point(s): 1/ Nodule diagnosis at P03277 imaging (HCC, not HCC specify) will be assessed: -on a maximum of 3 hepatic nodules per subject -based on visual qualitative analysis of P03277 triphasic imaging (arterial, portal and delayed phases) showing HCC typical hallmarks according to EASL/EORTC criteria (arterial hypervascularization and portal wash-out or delayed wash-out) -by two expert readers. In case of discordance, a consensus diagnostic will be obtained 2/The standard of reference for diagnosing liver nodules (HCC, other malignant, regenerative or dysplastic nodule, benign, uncertain) will be given by the site according to their standard of care and according to adapted EASL/EORTC diagnostic criteria, considering previous contrast enhanced imaging (CT and/or MRI) and/or histology analysis and/or the more recent AFP results available: HCC will be considered when: -Histology is positive for HCC -Or Nodule identified and characterized by typical features using two different triphasic contrast enhanced modalities. Typical features are arterial hypervascularization and portal wash-out or delayed wash-out -Or AFP>200ng/mL in a presence of a single nodule Other diagnosis than HCC could be based on imaging only and/or histology. ;Timepoint(s) of evaluation of this end point: 1/ P03277 imaging will be done at Day 0. Diagnosis (HCC, not HCC specify) will be assessed during expert Reading (after the end of subjects inclusions) 2/ Diagnosis reference will be based on previous images (Day-21 to Day-7) and be assessed at visit 3 (safety visit D+1)) or at optional Visit 4 between 3 days after P0327 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy parameters - Technical adequacy - Visualization of biliary and liver abnormalities - Number of liver lesions detected - Qualitative evaluation (lesion intensity, presence of intralesional iron and fat and visualization of perilesional capsule) -Qualitative evaluation at available very delayed image, liver enhancement relative to the unenhanced fat-suppressed GRE T1 sequence - Quantitative evaluation : SI measurements in nodules, liver, background, aorta and the portal vein for SNR CNR LE Safety profile - Adverse events - Injection site tolerance - clinical laboratory parameters (Hematology, biochemistry) -vital signs ;Timepoint(s) of evaluation of this end point: Efficacy parameters: - on-site Reading at Day 0; - expert Reading (after the end of subjects inclusions) Safety profile - Adverse events up to Day+1. AEs that the investigator considers related to P03277 and/or study procedures will be recorded at optional V4. -Injection site tolerance : during injection up to 30mn and Day+1 - clinical laboratory parameters : baseline at screening or inclusion and Day+1 - vital signs : prior to P03277 administration and at 30+/-5 minutes following P03277 injection and at Day +1 | — |
Countries
France
Contacts
Public ContactMalychanh LE
GUERBET
Outcome results
None listed