Study to Evaluate the Safety and Preliminary Efficacy of 177Lu-OPS201 in NETs

NCT02592707 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: D-FR-01072-0012015-002867-41OPS-C-001
• Study Type: interventional
• Target: 40
• Locations: 7 countries
• Sites: 7

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.

Conditions

Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

  AE is defined as any untoward medical occurrence in a subject or clinical trial subject administered a medicinal product, which did not necessarily have a causal relationship with this treatment. A serious AE (SAE) was classified as any untoward medical occurrence that at any dose results in death; AE was life threatening; required inpatient hospitalization or prolonged existing hospitalization; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect; was an important medical event that may not result in death. TEAEs are defined as AEs that developed or worsened after start of treatment.

  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

• Number of Participants With Dose Limiting Toxicities (DLT)

  DLTs were defined as study medication-related AEs with a severity of Grade 3 or higher are considered DLT, with the exception of hair loss, lymphopenia, nonfebrile neutropenia lasting \<4 weeks and thrombocytopenia lasting \<4 weeks.

  From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks.

Secondary Outcomes (23)

• Maximum Uptake (%) of 177Lu-IPN01072 at Target Lesions and Discernible Organs in Cycle 1

  4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1

• Maximal Uptake (%) of 177Lu-IPN01072 in Blood in Cycle 1

  Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1

• Area Under the Concentration Time Curve (AUC) of 177Lu-IPN01072 in Discernible Organs in Cycle 1

  4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1

• AUC of 177Lu-IPN01072 in Blood in Cycle 1

  Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1

• Terminal Half-Life (T1/2) of Radioactivity Concentrations of the Radiopharmaceutical in Blood in Cycle 1

  Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1

Study Arms (1)

177Lu-IPN01072

EXPERIMENTAL

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

Drug: Satoreotide tetraxetan; Other: Amino acid solution; Other: Antiemetic

Interventions

Satoreotide tetraxetan DRUG

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

Also known as: 177Lu-OPS201, 177Lu-IPN01072

177Lu-IPN01072

Amino acid solution OTHER

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)

Also known as: OPS301, IPN60070, Arginine and lysine

177Lu-IPN01072

Antiemetic OTHER

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).

Also known as: Dexamethasone, Ondansetron

177Lu-IPN01072

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Patients of either gender, aged ≥ 18 years.
• 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.).
• 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.
• Karnofsky performance score ≥ 60.
• Life expectancy of at least 6 months.
• 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
• 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.
• 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.
• Measurable disease based on RECIST v1.1.
• 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.
• Calculated GFR ≥ 55 mL/min.

You may not qualify if:

• Known hypersensitivity to 177Lu, to DOTA, to JR11 or to any of the excipients of 177Lu-OPS201.
• Any previous peptide receptor radionuclide therapy (PRRT).
• Diagnosis of thymic NET.
• Presence of active infection at screening or history of serious infection within the previous 6 weeks.
• Administration of any other investigational medicinal product within 60 days prior to entry.
• Prior or planned administration of a therapeutic radiopharmaceutical within 8 half-lives of the radionuclide including any time during the current study.
• Any extensive radiotherapy ≤ 3 months before enrolment.
• Chemotherapy ≤ 3 months before enrolment.
• Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject at high risk of renal toxicity during the study as assessed by the investigator.
• 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).
• 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.
• 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
• 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.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (9)

MD Anderson Cancer Center, Department of Nuclear Medicine

Houston, Texas, 77030, United States

Location

Peter MacCallum Cancer Centre, Molecular Imaging and Targeted Therapeutics Laboratory

East Melbourne, 3002, Australia

Location

Ramsay Hollywood Private Hospital, Department of Nuclear Medicine

Perth, 6009, Australia

Location

University Hospital Vienna, Department of Nuclear Medicine

Vienna, 1090, Austria

Location

CHU de Quebec - Universite Laval Research Center, Department of Radiology and Nuclear Medicine

Québec, G1R2J6, Canada

Location

University Hospital Aarhus, Department of Hepatology and Gastroenterology

Aarhus, 8000, Denmark

Location

CHU de Nantes, Hotel Dieu, Service de Medecine Nucleaire

Nantes, 44093, France

Location

University Hospital Basel, Department of Nuclear Medicine

Basel, 4031, Switzerland

Location

Royal Free Hospital, Department of Nuclear Medicine

London, NW3 2QG, United Kingdom

Location

Related Publications (2)

• Schurrle SB, Eberlein U, Ansquer C, Beauregard JM, Durand-Gasselin L, Gronbaek H, Haug A, Hicks RJ, Lenzo NP, Navalkissoor S, Nicolas GP, Pais B, Volteau M, Wild D, McEwan A, Lassmann M. Dosimetry and pharmacokinetics of [177Lu]Lu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2024 Jul;51(8):2428-2441. doi: 10.1007/s00259-024-06682-1. Epub 2024 Mar 26.

  PMID: 38528164 DERIVED

• Wild D, Gronbaek H, Navalkissoor S, Haug A, Nicolas GP, Pais B, Ansquer C, Beauregard JM, McEwan A, Lassmann M, Pennestri D, Volteau M, Lenzo NP, Hicks RJ. A phase I/II study of the safety and efficacy of [177Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2023 Dec;51(1):183-195. doi: 10.1007/s00259-023-06383-1. Epub 2023 Sep 18.

  PMID: 37721581 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

177Lu-DOTA-JR11; amino-acid, glucose, and electrolyte solution; arginyllysine; Antiemetics; Dexamethasone; Ondansetron

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Gastrointestinal Agents; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Limitations and Caveats

Due to strategic reasons, the Ipsen management team decided to early terminate the D-FR-01072-001 / OPS-C-001 study. This decision was not due to any safety or tolerability concern, or any event associated with the use of the study drug.

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen Pharma

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2015
• First Posted: October 30, 2015
• Study Start: March 6, 2017
• Primary Completion: February 22, 2022
• Study Completion: February 22, 2022
• Last Updated: July 19, 2023
• Results First Posted: July 19, 2023

Record last verified: 2023-07

Locations

FR (1); AU (1); CH (1); DK (1); GB (1); CA (1); US (1)