An international multi-center, open-label study to evaluate safety, tolerability, biodistribution (distribution in the body), dosimetry (to calculate the radiation exposure of patients) and preliminary efficacy of 177Lu-OPS201 for the therapy of somatostatin receptor positive neuroendocrine tumours (NETs).
- Conditions
- euroendocrine tumors (NETs)MedDRA version: 21.0Level: PTClassification code 10052399Term: Neuroendocrine tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]
- Registration Number
- EUCTR2015-002867-41-DK
- Lead Sponsor
- Ipsen Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 55
1. Written informed consent
2. Subjects of either gender, aged = 18 years
3. Women of childbearing potential (not surgically sterile or less than 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 6 months after the last dose. Acceptable methods of contraception include abstinence, or double contraception: steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method (intrauterine device, condom etc.).
4. Male subjects must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 6 months after the last activity administration.
5. Karnofsky performance score = 60
6. Life expectancy of at least 6 months
7. Histologically confirmed diagnosis of
- unresectable GEP NET (Grade I and Grade II according to WHO classification (2010), functioning and nonfunctioning)
- unresectable lung NET Grade I and Grade II (low and intermediate grade) (Klimstra et al 2010)
- unresectable typical lung carcinoid or atypical lung carcinoid are acceptable (with the exception of Large Cell Bronchila Neuroendocrine Neoplasms and Small Cell Lung Cancers (Caplin 2015).
- malignant, unresectable pheochromocytoma or paraganglioma
- subjects, who have histologically confirmed NET, but no clear localization of their primary tumor can be included.
8. Documentation of progressive disease based on RECIST v1.1 under prior anti-tumor therapy within 6 months of Visit 1 Day 1 (although the progression might have occured more than 6 months before Visit 1 Day 1). Subjects should not have received further anti-tumor therapy once disease progression is documented. All images should be sent to the imaging core laboratory.
9. In countries where sunitinib or everolimus are marketed, subjects with GEP NET and lung NET will be progressive under this prior anti-tumor treatment for the respective indication. Subjects not suitable for everolimus/sunitinib therapy according to a tumor board decision (or comparable local practice) may also be enrolled into the study. Subjects having everolimus/sunitinib therapy should have a wash-out phase of = 4 weeks before the first treatment.
10. Measurable disease based on RECIST v1.1.
11. For Part A: Confirmed presence of somatostatin receptors on technically evaluable tumor lesions documented by a positive SRS* performed within 6 months prior of Visit 1 Day 1
* presence of at least one lesion that is = 20 mm in the longest dimension (as measured on correlative CT or MRI) and with a maximum Standardized Uptake Value (SUVmax) of = 2x the SUVmean of the liver background on 68Ga-PET imaging or a score of 3” or 4” according to the Krenning scale on 111In-SPECT Imaging.
For Part B: Confirmed presence of sstr on technically evaluable tumour lesions documented by a positive SRS*. If this has not been performed within 6 months of Visit 1 Day 1, then it must be repeated during screening.
*presence of at least two lesions that are =20 mm in the longest Dimension (as measured on correlative CT or MRI) with a maximum standardized uptake value (SUVmax) of = 2x the SUVmean of the liver background on 68Ga-PET imaging or a score of 3” or 4” according to the Krenning scale on SPECT Imaging.
12. Calculated glomerular filtration rate (GFR) = 55 mL/min
13. Blood test results as follows:
a. Leukocy
1. Known hypersensitivity to 177Lu, DOTA, JR11 or to any of the excipients of 177Lu-OPS201.
2. Any previous PRRT.
3. Diagnosis of thymic NET.
4. Presence of active infection at screening, or history of serious infection within the previous 6 weeks.
5. Administration of any other investigational medicinal product (IMP) within 60 days prior to entry (Visit 1 Day 1).
6. Prior or planned administration of a therapeutic radiopharmaceutical within 8 half-lives of the radionuclide including any time during the current study.
7. Any extensive radiotherapy = 3 months before first IRPP administration
8. Chemotherapy = 3 months before first IRPP Administration
9. For Part B: Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject at high risk of renal toxicity during the study as assessed by the investigator
10a. Pregnant or breast-feeding women. A serum pregnancy test will be performed at the start of the study for all female subjects of childbearing potential (i.e. not surgically sterile or up to 2 years postmenopausal).
11. Any uncontrolled significant medical, psychiatric or surgical condition (active infection (including subject with known hepatitis B or hepatitis C and subjects with known human immunodeficiency virus (HIV) positive), unstable angina pectoris, cardiac arrhythmia, poorly controlled hypertension, poorly controlled diabetes mellitus (glycated haemoglobin (HbA1c) =9%), uncontrolled congestive heart disease, etc.) or laboratory findings that, in the opinion of the investigator, might jeopardise the subject's safety or that would limit compliance with the objectives and assessments of the study. Note: the subject should be able to tolerate high volume load.
12. Current history of any malignancy other than NET within 5 years of enrolment except for fully-resected non-melanoma skin cancer or cervical cancer in situ
13. 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method