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

NCT ID: NCT02592707

Last Updated: 2023-07-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-06
• Study Completion Date: 2022-02-22

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

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

177Lu-IPN01072

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

Group Type: EXPERIMENTAL

Satoreotide tetraxetan

Intervention Type: DRUG

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

Amino acid solution

Intervention Type: 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)

Antiemetic

Intervention Type: 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).

Interventions

Satoreotide tetraxetan

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

Intervention Type: DRUG

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)

Intervention Type: OTHER

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 Type: OTHER

Other Intervention Names

177Lu-OPS201; 177Lu-IPN01072; OPS301; IPN60070; Arginine and lysine; Dexamethasone; Ondansetron

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ipsen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

MD Anderson Cancer Center, Department of Nuclear Medicine

Houston, Texas, United States

Peter MacCallum Cancer Centre, Molecular Imaging and Targeted Therapeutics Laboratory

East Melbourne, , Australia

Ramsay Hollywood Private Hospital, Department of Nuclear Medicine

Perth, , Australia

University Hospital Vienna, Department of Nuclear Medicine

Vienna, , Austria

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

Québec, , Canada

University Hospital Aarhus, Department of Hepatology and Gastroenterology

Aarhus, , Denmark

CHU de Nantes, Hotel Dieu, Service de Medecine Nucleaire

Nantes, , France

University Hospital Basel, Department of Nuclear Medicine

Basel, , Switzerland

Royal Free Hospital, Department of Nuclear Medicine

London, , United Kingdom

Countries

United States; Australia; Austria; Canada; Denmark; France; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38528164 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37721581 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-002867-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OPS-C-001

Identifier Type: OTHER

Identifier Source: secondary_id

D-FR-01072-001

Identifier Type: -

Identifier Source: org_study_id