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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02592707




Registration number
NCT02592707
Ethics application status
Date submitted
15/10/2015
Date registered
30/10/2015
Date last updated
19/07/2023

Titles & IDs
Public title
Study to Evaluate the Safety and Preliminary Efficacy of 177Lu-OPS201 in NETs
Scientific title
An International, Multicenter, Open-label Study to Evaluate Safety, Tolerability, Biodistribution, Dosimetry and Preliminary Efficacy of 177Lu-OPS201 for the Therapy of Somatostatin Receptor-positive Neuroendocrine Tumors (NETs)
Secondary ID [1] 0 0
2015-002867-41
Secondary ID [2] 0 0
D-FR-01072-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuroendocrine Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Satoreotide tetraxetan
Other interventions - Amino acid solution
Other interventions - Antiemetic

Experimental: 177Lu-IPN01072 - 177Lu-IPN01072 administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles)


Treatment: Drugs: Satoreotide tetraxetan
Satoreotide tetraxetan administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles)

Other interventions: Amino acid solution
Given as an auxiliary product the day of the IMP infusion for safety reasons to protect the renal function.

Centres can use their established amino acid infusion or Ipsen amino acid solution (auxiliary medical product OPS301)

Other interventions: Antiemetic
To counteract the known side effects of the amino acid infusion, such as nausea, dexamethasone (antiemetic) and as-required ondansetron will be administered 15 to 30 minutes before the start of the amino acid infusion (unless there are contraindications for these drugs).
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Timepoint [1] 0 0
From the start of the first study medication (Cycle 1 Day 1) up to 6 months after the last dose of study medication, maximum of 33 months
Primary outcome [2] 0 0
Number of Participants With Dose Limiting Toxicities (DLT)
Timepoint [2] 0 0
From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks.
Secondary outcome [1] 0 0
Maximum Uptake (%) of 177Lu-IPN01072 at Target Lesions and Discernible Organs in Cycle 1
Timepoint [1] 0 0
4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
Secondary outcome [2] 0 0
Maximal Uptake (%) of 177Lu-IPN01072 in Blood in Cycle 1
Timepoint [2] 0 0
Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
Secondary outcome [3] 0 0
Area Under the Concentration Time Curve (AUC) of 177Lu-IPN01072 in Discernible Organs in Cycle 1
Timepoint [3] 0 0
4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
Secondary outcome [4] 0 0
AUC of 177Lu-IPN01072 in Blood in Cycle 1
Timepoint [4] 0 0
Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
Secondary outcome [5] 0 0
Terminal Half-Life (T1/2) of Radioactivity Concentrations of the Radiopharmaceutical in Blood in Cycle 1
Timepoint [5] 0 0
Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
Secondary outcome [6] 0 0
Highest Absorbed Dose of 177LU-IPN01072 to Each Discernible Organ in Cycle 1
Timepoint [6] 0 0
4, 24, 48, 72 to 96 and 144 to 168 hours post infusion in Cycle 1
Secondary outcome [7] 0 0
Specific Absorbed Dose Per Organ and Lesions of 177Lu-IPN01072 in Cycle 1
Timepoint [7] 0 0
4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
Secondary outcome [8] 0 0
Cumulative Absorbed Organ Doses of 177Lu-IPN01072 in Cycles 1 and 3
Timepoint [8] 0 0
4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycles 1 and 3
Secondary outcome [9] 0 0
Cumulative Amount of Lu-177 Radioactivity Excreted Into the Urine (0 to 48 Hours) [Ae (0-48h)] in Cycle 1
Timepoint [9] 0 0
0 to 6 hours, 6 to 24 hours, 24 to 48 hours post-infusion in Cycle 1 of Part A; 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 of Part B.
Secondary outcome [10] 0 0
Time to Reach Maximum Plasma Concentration (Tmax) of IPN01072 in Cycle 1
Timepoint [10] 0 0
Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1
Secondary outcome [11] 0 0
Maximum Observed Plasma Concentration (Cmax) of IPN01072 in Cycle 1
Timepoint [11] 0 0
Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1
Secondary outcome [12] 0 0
AUC From Time Zero to Infinity (AUCinf) of IPN01072 in Cycle 1
Timepoint [12] 0 0
Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1
Secondary outcome [13] 0 0
T1/2 of IPN01072 in Cycle 1
Timepoint [13] 0 0
Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1
Secondary outcome [14] 0 0
Apparent Total Plasma Clearance of IPN01072 (Total CL) in Cycle 1
Timepoint [14] 0 0
Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1
Secondary outcome [15] 0 0
Apparent Volume of Distribution During Terminal Phase (Vz) of IPN01072 in Cycle 1
Timepoint [15] 0 0
Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1
Secondary outcome [16] 0 0
Ae (0-48h) of IPN01072 in Cycle 1
Timepoint [16] 0 0
0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 of Part B
Secondary outcome [17] 0 0
Fraction of IPN01072 Excreted Into the Urine (Fe) in Cycle 1
Timepoint [17] 0 0
0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 in Part B
Secondary outcome [18] 0 0
Overall Response Rate (ORR)
Timepoint [18] 0 0
From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.
Secondary outcome [19] 0 0
Disease Control Rate (DCR)
Timepoint [19] 0 0
From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.
Secondary outcome [20] 0 0
Best Overall Response
Timepoint [20] 0 0
From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.
Secondary outcome [21] 0 0
Progression Free Survival (PFS)
Timepoint [21] 0 0
From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.
Secondary outcome [22] 0 0
Change From Baseline in Quality of Life (QoL) Questionnaire (QLQ)-C30 at EOCT Visit
Timepoint [22] 0 0
Baseline (Day 1) and EOCT visit (30 months)
Secondary outcome [23] 0 0
Change From Baseline in QLQ Gastro-intestinal. Neuroendocrine Tumour (GI.NET)21 at EOCT Visit
Timepoint [23] 0 0
Baseline (Day 1) and EOCT visit (30 months)

Eligibility
Key inclusion criteria
1. Written informed consent.
2. Patients 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 patients 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, Annex 01), functioning and non-functioning).
* unresectable "typical lung carcinoid" or "atypical lung carcinoid" are acceptable (with the exception of Large Cell Bronchial Neuroendocrine Neoplasms and Small Cell Lung Cancers) (Caplin 2015).
* malignant, unresectable pheochromocytoma or paraganglioma
8. Documentation of progressive disease based on RECIST v1.1 under prior anti-tumor therapy within 6 months of entry in the study (although the progression might have occurred more than 6 months before study entry). Patients should not have received further anti-tumor therapy once disease progression is documented. The images of this evaluation should be available for TGR evaluation.
9. In countries where sunitinib or everolimus are marketed, patients with GEP NET and lung NET will be progressive under this prior anti-tumor treatment for the respective indication. Patients not suitable for everolimus/sunitinib therapy according to a tumor board decision (or comparable local practice) may also be enrolled into the study. Patients 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. Confirmed presence of somatostatin receptors on technically evaluable tumor lesions documented by a positive Somatostatin Receptor Scan performed within 6 months prior to enrolment in the study.
12. Calculated GFR = 55 mL/min.
13. Blood test results as follows:

* Leukocytes: = 4*10^9/L
* Erythrocytes: = 3.5*12^9/L
* Platelets: = 100*10^9/L
* Albumin: > 30 g/L
* ALT, AST, AP: = 5 times ULN (upper limit of normal)
* Bilirubin: = 2 times ULN (2x 1.1 mg/dL)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known hypersensitivity to 177Lu, to DOTA, to JR11 or to any of the excipients of 177Lu-OPS201.
2. Any previous peptide receptor radionuclide therapy (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 within 60 days prior to entry.
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 enrolment.
8. Chemotherapy = 3 months before enrolment.
9. Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject at high risk of renal toxicity during the study as assessed by the investigator.
10. Pregnant or breast-feeding women: A pregnancy test will be performed at the start of the study for all female patients 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, unstable angina pectoris, cardiac arrhythmia, poorly controlled hypertension, poorly controlled diabetes mellitus [HbA1c =9%], uncontrolled congestive heart disease, etc.) or laboratory findings that, in the opinion of the investigator, might jeopardize the patient's safety or that would limit compliance with the objectives and assessments of the study. Note: the patient 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. Current history of malignancy; patients with a secondary tumor in remission of > 5 years can be included
13. Any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/03/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/02/2022
Sample size
Target
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre, Molecular Imaging and Targeted Therapeutics Laboratory - East Melbourne
Recruitment hospital [2] 0 0
Ramsay Hollywood Private Hospital, Department of Nuclear Medicine - Perth
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
Austria
State/province [2] 0 0
Vienna
Country [3] 0 0
Canada
State/province [3] 0 0
Québec
Country [4] 0 0
Denmark
State/province [4] 0 0
Aarhus
Country [5] 0 0
France
State/province [5] 0 0
Nantes
Country [6] 0 0
Switzerland
State/province [6] 0 0
Basel
Country [7] 0 0
United Kingdom
State/province [7] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ipsen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this clinical phase I/II study was to investigate the safety and tolerability of satoreotide tetraxetan (177Lu-IPN01072, formerly known as 177Lu-OPS201) used for the treatment of patients with neuroendocrine tumors (NETs). The secondary objectives of this study were the assessment of biodistribution, dosimetry and preliminary efficacy of satoreotide tetraxetan.
Trial website
https://clinicaltrials.gov/study/NCT02592707
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ipsen Medical Director
Address 0 0
Ipsen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02592707