Clinical trial NCT02592707: Study to Evaluate the Safety and Preliminary Efficacy of 177Lu-OPS201 in NETs
Official 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Neuroendocrine Tumors
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2015-10-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: 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
measure: Number of Participants With Dose Limiting Toxicities (DLT)
timeFrame: From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks.
Secondary outcomes:
measure: Maximum Uptake (%) of 177Lu-IPN01072 at Target Lesions and Discernible Organs in Cycle 1
timeFrame: 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
measure: Maximal Uptake (%) of 177Lu-IPN01072 in Blood in Cycle 1
timeFrame: Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
measure: Area Under the Concentration Time Curve (AUC) of 177Lu-IPN01072 in Discernible Organs in Cycle 1
timeFrame: 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
measure: AUC of 177Lu-IPN01072 in Blood in Cycle 1
timeFrame: Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
measure: Terminal Half-Life (T1/2) of Radioactivity Concentrations of the Radiopharmaceutical in Blood in Cycle 1
timeFrame: Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
measure: Highest Absorbed Dose of 177LU-IPN01072 to Each Discernible Organ in Cycle 1
timeFrame: 4, 24, 48, 72 to 96 and 144 to 168 hours post infusion in Cycle 1
measure: Specific Absorbed Dose Per Organ and Lesions of 177Lu-IPN01072 in Cycle 1
timeFrame: 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1
measure: Cumulative Absorbed Organ Doses of 177Lu-IPN01072 in Cycles 1 and 3
timeFrame: 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycles 1 and 3
measure: Cumulative Amount of Lu-177 Radioactivity Excreted Into the Urine (0 to 48 Hours) [Ae (0-48h)] in Cycle 1
timeFrame: 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.
measure: Time to Reach Maximum Plasma Concentration (Tmax) of IPN01072 in Cycle 1
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of IPN01072 in Cycle 1
timeFrame: 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
measure: AUC From Time Zero to Infinity (AUCinf) of IPN01072 in Cycle 1
timeFrame: 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
measure: T1/2 of IPN01072 in Cycle 1
timeFrame: 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
measure: Apparent Total Plasma Clearance of IPN01072 (Total CL) in Cycle 1
timeFrame: 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
measure: Apparent Volume of Distribution During Terminal Phase (Vz) of IPN01072 in Cycle 1
timeFrame: 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
measure: Ae (0-48h) of IPN01072 in Cycle 1
timeFrame: 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 of Part B
measure: Fraction of IPN01072 Excreted Into the Urine (Fe) in Cycle 1
timeFrame: 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 in Part B
measure: Overall Response Rate (ORR)
timeFrame: 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.
measure: Disease Control Rate (DCR)
timeFrame: 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.
measure: Best Overall Response
timeFrame: 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.
measure: Progression Free Survival (PFS)
timeFrame: 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.
measure: Change From Baseline in Quality of Life (QoL) Questionnaire (QLQ)-C30 at EOCT Visit
timeFrame: Baseline (Day 1) and EOCT visit (30 months)
measure: Change From Baseline in QLQ Gastro-intestinal. Neuroendocrine Tumour (GI.NET)21 at EOCT Visit
timeFrame: Baseline (Day 1) and EOCT visit (30 months)
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center, Department of Nuclear Medicine
state: Texas
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre, Molecular Imaging and Targeted Therapeutics Laboratory
city: Perth
country: Australia
facility: Ramsay Hollywood Private Hospital, Department of Nuclear Medicine
city: Vienna
country: Austria
facility: University Hospital Vienna, Department of Nuclear Medicine
city: Québec
country: Canada
facility: CHU de Quebec - Universite Laval Research Center, Department of Radiology and Nuclear Medicine
city: Aarhus
country: Denmark
facility: University Hospital Aarhus, Department of Hepatology and Gastroenterology
city: Nantes
country: France
facility: CHU de Nantes, Hotel Dieu, Service de Medecine Nucleaire
city: Basel
country: Switzerland
facility: University Hospital Basel, Department of Nuclear Medicine
city: London
country: United Kingdom
facility: Royal Free Hospital, Department of Nuclear Medicine
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: