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

• ClinicalTrials.gov Identifier: NCT02592707
• Recruitment Status: Terminated
• First Posted: October 30, 2015
• Last Update Posted: March 31, 2022
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

Study Description

Brief Summary:

The purpose of this clinical phase I/II study is to investigate the safety and tolerability of 177Lu-OPS201 used for the treatment of patients with neuroendocrine tumors (NETs). Secondary objectives of these study are the assessment of biodistribution, dosimetry and preliminary efficacy of 177Lu-OPS201.

Condition or disease	Intervention/treatment	Phase
Neuroendocrine Tumors	Drug: Satoreotide tetraxetan; Other: Amino acid solution; Other: Antiemetic	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: March 6, 2017
• Actual Primary Completion Date: February 22, 2022
• Actual Study Completion Date: February 22, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: 177Lu-OPS201; 177Lu-OPS201 will be administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles)

Drug: Satoreotide tetraxetan; Satoreotide tetraxetan will be administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles); Other Name: 177Lu-OPS201; Other: 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 Name: OPS301; 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).; Other Names: Dexamethasone; Ondansetron

Outcome Measures

Primary Outcome Measures :

1. Safety and Tolerability of 177Lu-OPS201 assessed by number of patients with treatment related adverse events using CTCAE v5.0 [ Time Frame: during the whole study period of 34 months ]

Secondary Outcome Measures :

1. Area under the curve (AUC) of 177Lu-OPS201 per cycle in discernible thoracic and abdominal organs, target lesions and blood [ Time Frame: during the core study period of 10 months ]
2. Maximal uptake (achieved in %) at the target lesions per cycle. [ Time Frame: during the core study period of 10 months ]
3. Maximal uptake in discernible organs (%) and blood (%/mL) per cycle. [ Time Frame: during the core study period of 10 months ]
4. Organs receiving the highest absorbed dose (Gy) for each cycle. [ Time Frame: during the core study period of 10 months ]
5. Specific absorbed dose per organ (achieved in Gy/GBq) for each cycle. [ Time Frame: during the core study period of 10 months ]
6. Cumulative absorbed organ doses (achieved in Gy). [ Time Frame: during the core study period of 10 months ]
7. Preliminary therapeutic efficacy of 177Lu-OPS201 assessed by tumor response based on RECIST v1.1 [ Time Frame: during the whole study period of 34 months ]
8. Preliminary therapeutic efficacy of 177Lu-OPS201 assessed by monitoring of PFS (based on RECIST v1.1 status) [ Time Frame: during the whole study period of 34 months ]
9. Quality of Life (QoL) questionnaire [ Time Frame: during the core study period of 10 months ]
10. Terminal half-life of radioactivity concentrations of the radiopharmaceutical in blood [ Time Frame: during the first 7 days of cycle 1 of the core study period ]
11. PK parameters of OPS201, if OPS201 levels are measurable in plasma and urine. [ Time Frame: during the first 3 days of cycle 1 of the core study period ]
    PK parameters of OPS201(including, but not limited to, maximum observed concentration (Cmax), AUC, elimination half-life (t1/2), apparent total body clearance of the drug from plasma (CL), apparent volume of distribution (Vd), cumulative amount of unchanged drug excreted into the urine (Ae), renal clearance of the drug from plasma (CLR)) will be derived using the non-compartmental approach on the individual plasma concentration-time profiles of OPS201 and on the individual urine concentrations

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Texas

MD Anderson Cancer Center, Department of Nuclear Medicine

Houston, Texas, United States, 77030

Australia

Peter MacCallum Cancer Centre, Molecular Imaging and Targeted Therapeutics Laboratory

East Melbourne, Australia, 3002

Ramsay Hollywood Private Hospital, Department of Nuclear Medicine

Perth, Australia, 6009

Austria

University Hospital Vienna, Department of Nuclear Medicine

Vienna, Austria, 1090

Canada

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

Québec, Canada, G1R2J6

Denmark

University Hospital Aarhus, Department of Hepatology and Gastroenterology

Aarhus, Denmark, 8000

France

CHU de Nantes, Hotel Dieu, Service de Medecine Nucleaire

Nantes, France, 44093

Switzerland

University Hospital Basel, Department of Nuclear Medicine

Basel, Switzerland, 4031

United Kingdom

Royal Free Hospital, Department of Nuclear Medicine

London, United Kingdom, NW3 2QG

Sponsors and Collaborators

Ipsen

Investigators

• Study Director: Ipsen Medical Director; Ipsen

More Information

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT02592707
• Other Study ID Numbers: D-FR-01072-001; 2015-002867-41 ( EudraCT Number ); OPS-C-001 ( Other Identifier: Initial sponsor study ID )
• First Posted: October 30, 2015
• Last Update Posted: March 31, 2022
• Last Verified: March 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Dexamethasone; Ondansetron; Antiemetics; 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; Anti-Inflammatory Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antipruritics; Dermatologic Agents; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Chelating Agents; Sequestering Agents