| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Neuroendocrine tumors (NETs), neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. NETs occur mainly in the gastrointestinal tract and in the pancreas (GEP). |
|
| E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10052399 |
| E.1.2 | Term | Neuroendocrine tumour |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To define the optimal dose range for peptide mass and radioactivity of 68Ga-OPS202 based on detected lesions in adult subjects with somatostatin receptor 2 (sstr2) positive gastroenteropancreatic neuroendocrine tumour (GEP-NET). |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives:
- To further refine the optimal dose range for peptide mass and radioactivity of 68Ga-OPS202 based on quantitative maximum standardized uptake value (SUVmax) and other quality parameters.
- To describe the safety and tolerability of diagnostic 68Ga-OPS202 in subjects with sstr2-positive GEP-NET.
- To characterize the pharmacokinetics (PK) of OPS202 in subjects with GEP NET.
Exploratory objectives:
- To provide preliminary estimates of the sensitivity of 68Ga-OPS202 positron emission tomography/computed tomography (PET/CT) scan imaging, as well as SUV ratio [SUVmax lesion/ SUVmean reference tissue], and signal-to-noise ratios (SNR). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
(1) Men or women aged 18 years or older
(2) Subjects with pathologically confirmed, well differentiated functioning or non-functioning metastatic GEP-NET (Grade I and II as per WHO classification 2010)
(3) Subjects with a confirmed presence of somatostatin receptors (type 2) on technically evaluable tumour lesions documented by a positive Somatostatin Receptor Scan acquired within 6 months prior to screening (Visit 1) and showing minimally two lesions in at least one of the key organs namely liver, lymph nodes, bone or lungs; these images shall be available to be sent to the ICL electronically to ascertain quality and admissibility
(4) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
(5) Subjects with body weight between 50 kg (110 lb) and 110 kg (243 lb), inclusive
(6) Adequate bone marrow, liver and renal function, with:
• Calculated Glomerular filtration rate (GFR) ≥ 45 mL/min
• Albumin: > 30 g/L
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP): ≤ 5 times upper limit of normal (ULN)
• Bilirubin: ≤ 3 times ULN (3 × 1.1 mg/dL)
• Leukocytes: ≥ 3*109/L and neutrophils ≥ 1*109/L
• Erythrocytes: ≥ 3.5*1012/L
• Platelets: ≥ 90*109/L
(7) Signed written informed consent prior to any study-related procedures |
|
| E.4 | Principal exclusion criteria |
(1) Subjects with fewer than five lesions in total and more than 25 lesions/organ detected by the somatostatin receptor positive scan in key organs: liver, lymph nodes, bone or lung
(2) Subject who have received treatment of any somatostatin analogue, including Somatuline® Autogel® /Depot®, Sandostatin® LAR within 28 days, and Sandostatin® within 24 hours prior to first 68Ga-OPS202 administration.
(3) Presence of active infection at screening or history of serious infection within the previous 6 weeks prior to the first 68Ga-OPS202 administration
(4) Prior or planned administration of a radiopharmaceutical within 8 half-lives of the radionuclide
(5) Clinically relevant trauma within 2 weeks prior to first 68Ga-OPS202 administration
(6) Known hypersensitivity to NODAGA, to Gallium-68, to JR11 or to any of the excipients of 68Ga-OPS202
(7) History of, or current active allergic or autoimmune disease, including asthma or any condition requiring long-term use of systemic corticosteroids
(8) Known human immunodeficiency virus (HIV) or positive serology for HIV, hepatitis B and C
(9) Any condition that precludes the proper performance of PET and/or CT scan:
a) Subjects who are not able to tolerate the CT contrast agent,
b) Subjects with metal implants or arthroplasty, or any other objects that might interfere with the PET and/or CT analysis
c) Subjects unable to raise arms for prolonged imaging purposes
d) Subjects unable to lie still for the entire imaging time
e) Subjects weighing greater than 110 kg (243 lb)
(10) Administration of another investigational medicinal product within 30 days prior to first 68Ga-OPS202 administration
(11) Female subjects who are pregnant, breast feeding or of childbearing potential not willing to practice effective contraceptive techniques during the study treatment period and for 30 days after the last dose of 68Ga-OPS202 administration; pregnancy test must be performed at the start of the study and prior to each 68Ga-OPS202 administration
(12) Subjects who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study, including any mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude
(13) Subject who experienced a previous cancer (except basocellular carcinoma of the skin and/or in situ carcinoma of the cervix/uterus and/or subjects treated with curative intent and free from disease for more than 5 years) other than NET |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy:
For each combination of injected peptide/radioactivity dose ranges, differences in relative lesion counts derived from a 2 × 3 factorial analysis measuring the ratio of the number of lesions detected by 68Ga-OPS202 to the number of lesions assessed by standard-of-truth (descriptive analyses).
The standard-of-truth in the present study is the CT scan images acquired at Visit 2 and Visit 3. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 68Ga-OPS202 PET/CT imaging will be taken at Visit 2 (Day 1) and Visit 3 (Day 16-22) |
|
| E.5.2 | Secondary end point(s) |
I- Secondary endpoints:
Efficacy:
- For each combination of injected peptide/radioactivity dose ranges, differences in image quality derived from a 2 × 3 factorial analysis measuring the tumour-to-background ratio in each of the major anatomic sites (i.e. descriptive analyses for liver, lymph nodes, bone and lungs)
- Differences in lesion SUVmax between the two peptide mass dose ranges and the three radioactivity dose ranges measured in the most avid lesions (descriptive analyses for up to a maximum of five lesions per organ in liver, lymph nodes, bone and lungs)
- Differences of absolute number of lesions between the two peptide mass dose ranges and the three radioactivity dose ranges detected in each of the following anatomic sites:
o Primary site of GEP-NET
o Lymph nodes
o Liver
o Axial/appendicular skeleton
o Lungs
Safety:
- Proportion of subjects experiencing at least one AE of any grade according to NCI-CTCAE v5.0), including any SAEs and suspected unexpected serious adverse reactions (SUSARs)
- Proportion of subjects experiencing at least one AE of grade ≥3 according to NCI-CTCAE
- Clinically significant changes in physical examination, vital signs, ECG and laboratory findings, which will be recorded by the investigator as AEs
II- Exploratory endpoints:
Efficacy:
- Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging of GEP-NETs by both subject-based and lesion-based analysis compared to standard-of-truth
- Comparison to sstr2 agonist positive scan results will be computed for sensitivity analysis
- Differences in SUVmax ratios between the two peptide mass dose ranges and three radioactivity dose ranges for lesions
- SNR calculated from lesion-free volume of interest (VOI) in the liver: SUVmean/SUVSD between the three radioactivity doses.
Pharmacokinetics:
- Characterization of the PK of OPS202
o Cmax
o AUClast
o AUC∞
o elimination half-life (T1/2)
o total plasma clearance (CL)
o volume of distribution (V)
o excreted amount in the urine over specified time interval |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
I- Secondary:
Efficacy
68Ga-OPS202 PET/CT imaging will be taken at V2 and V3
Safety
- AEs will be assessed allthrough the study (V1 to V4)
- vital signs: V1 to V4 - 0.5, 1, 2 and 4 hours post injection
- physical examination: V1 to V4
- concomitant medication: from 3 months prior to start, V1 to V4 and until end of IMP related toxicity resolved in case of patient withdrawal
- ECG: V1, V4
II- Exploratory:
Efficacy
68Ga-OPS202 PET/CT imaging will be taken at V2 and V3
Pharmacokinetics
- blood PK sampling: V2, V3 - collected at baseline pre-dose (T0), 5min, 15 to 45min, 1h, 2h, 3h, 6h after IMP administration
- urine PK sampling: V2, V3 - collected at 0 to 3h and 3 to 6h after IMP administration |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| different dose of 68Ga-OPS202 |
|
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 3 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Austria |
| Denmark |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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