Treatment of Recurrent or Progressive Meningiomas With the Radiolabelled Somatostatin Antagonist 177Lu-satoreotide

NCT04997317 | Recruiting Phase 1

• 1 other identifier: 2019-00303; th21Wild2
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Meningiomas are known to be the most frequent intracranial neoplasms and account for approx. 25-33% of all intracranial tumours.Targeted radionuclide therapy with radiolabelled somatostatin analogues, also called Peptide Receptor Radionuclide Therapy (PRRT), has proven to be an effective treatment in metastatic intestinal neuroendocrine tumours and is currently used in advanced, recurrent or progressive meningiomas with promising results. In this study, the therapeutic index of a standard and newly developed radiolabelled somatostatin antagonist will be evaluated and compared in PRRT. In a second step, safety and efficacy of the latter will be assessed.

Conditions

Meningioma

Keywords

tumour; intercranial neoplasms; peptide receptor radionuclide therapy (PRRT); radiolabelled somatostatin antagonists; cancer; somatostatin receptors; 177Lu-DOTA-JR11; 77Lu-DOTATOC; somatostatin receptor subtype 2 (sstr2); 177Lu-satoreotide

Outcome Measures

Primary Outcomes (3)

• Change in Tumour-to-dose limiting organ dose ratio T-to-bone marrow: Therapeutic Index (Phase 0)

  Radiation Dosimetry of the Radiopharmaceuticals 177Lu-DOTA-JR11 and 177Lu-DOTATOC. In Phase 0 the primary objective is to assess the tumour-to-bone marrow dose ratios of 177Lu-DOTA-JR11 and 177Lu-DOTATOC. In order to get kinetic information of 177Lu- DOTA-JR11 and 177Lu-DOTATOC for this task total body scintigraphy and SPECT/CT of head and abdomen (phase 0 study) or only head (phase I/II study) are performed at different time points post injection 177Lu-DOTA-JR11 or 177Lu-DOTATOC.

  24, 48 and 168 hours (+/- 30 min up to 24 hours)

• Change in Tumour-to-dose limiting organ dose ratio T-to-kidney: Therapeutic Index (Phase 0)

  Radiation Dosimetry of the Radiopharmaceuticals 177Lu-DOTA-JR11 and 177Lu-DOTATOC. In Phase 0 the primary objective is to assess the tumour-to-kidney dose ratios of 177Lu-DOTA-JR11 and 177Lu-DOTATOC. In order to get kinetic information of 177Lu- DOTA-JR11 and 177Lu-DOTATOC for this task total body scintigraphy and SPECT/CT of head and abdomen (phase 0 study) or only head (phase I/II study) are performed at different time points post injection 177Lu-DOTA-JR11 or 177Lu-DOTATOC.

  24, 48 and 168 hours (+/- 30 min up to 24 hours)

• Assessment of treatment safety (phase I/II) by number of AEs graded according to CTCAE v5.0

  In Phase I/II the primary objective is to assess the safety considerations of patients treated with 177Lu-DOTA-JR11 after 3 - 5 cycles of 177Lu-DOTA-JR11 PRRT: AEs graded according to CTCAE v5.0

  About 1 hour before infusion up to 41 - 45 days after infusion

Secondary Outcomes (10)

• Tumour absorbed dose (Gy) (Phase 0 and phase I/II)

  up to 40 weeks

• Organ absorbed dose (Gy) (Phase 0)

  up to 40 weeks

• Organ and tumour residence time (Phase 0)

  up to 40 weeks

• Tumour-to-remaining organ dose ratio (Phase 0)

  up to 40 weeks

• Evaluation radiation doses (Phase 0 and Phase II)

  up to 40 weeks

Other Outcomes (1)

• Assessement of Progression-Free Survival (PFS) (Phase 0 and I/II))

  up to 12 months

Study Arms (3)

Phase 0: Group A

ACTIVE COMPARATOR

Cycle 1: 4.5 GBq 177Lu-DOTA-JR11 (300-1300 μg) will be administered once intravenously. Cycle 2: 4.5 GBq 177Lu-DOTATOC (≈200 μg) will be administered once intravenously (following a cross-over design). Cycle 3 and Cycle 4 will be performed for group A patients with 7.4 GBq 177Lu-DOTATOC (clinically established amount of activity). Cycle 3 and 4 are standard of care (i.e. not part of the study).

Drug: 177Lu-DOTA-JR11 (Phase 0); Cycle 1 and Cycle 2 (cross-over); Drug: 177Lu-DOTATOC (Phase 0); Cycle 1 and Cycle 2 (cross-over), Cycle 3 and 4

Phase 0: Group B

ACTIVE COMPARATOR

Cycle 1: 4.5 GBq 177Lu-DOTATOC (≈200 μg) will be administered once intravenously. Cycle 2: 4.5 GBq 177Lu-DOTA-JR11 (300-1300 μg) will be administered once intravenously (following a cross-over design). Cycle 3 and Cycle 4 will be performed for group B patients with 7.4 GBq 177Lu-DOTATOC (clinically established amount of activity). Cycle 3 and 4 are standard of care (i.e. not part of the study).

Drug: 177Lu-DOTA-JR11 (Phase 0); Cycle 1 and Cycle 2 (cross-over); Drug: 177Lu-DOTATOC (Phase 0); Cycle 1 and Cycle 2 (cross-over), Cycle 3 and 4

Phase I/II

ACTIVE COMPARATOR

3 cycles of 177Lu-DOTA-JR11 will be administered with an activity of 4.5-7.4 GBq. Two additional 177Lu-DOTA-JR11 treatment cycles can be performed if clinically indicated

Drug: 177Lu-DOTA-JR11 (Phase I/II)

Interventions

177Lu-DOTA-JR11 (Phase 0); Cycle 1 and Cycle 2 (cross-over) DRUG

177Lu-DOTA-JR11 has three main components, namely the somatostatin analogue JR11, the chemical chelator group DOTA and the beta emitter 177Lutetium (177Lu). In the Phase 0 part of the study 177Lu-DOTA-JR11 will be administered once intravenously. The activity of the first 2 cycles will be capped at 4.5 GBq (range: 4.2-4.6 GBq).

Phase 0: Group A; Phase 0: Group B

177Lu-DOTATOC (Phase 0); Cycle 1 and Cycle 2 (cross-over), Cycle 3 and 4 DRUG

177Lu-DOTATOC is a therapeutic medicinal product and has 3 main components (a) 177Lutetium (177Lu), a beta-emitting radionuclide with a half-life of 6.64 days; (b) DOTA, a chemical chelator group; and (c) TOC (= \[Tyr\]3-octreotide) an agonistic somatostatin analogue which binds to sstr2 and sstr5 receptors. In the Phase 0 part of the study 177Lu-DOTATOC will be administered once intravenously. The activity of the first 2 cycles will be capped at 4.5 GBq (range: 4.2-4.6 GBq). The remaining 2 cycles will be performed with an activity of 7.4 GBq 177Lu-DOTATOC (total number of cycles = 4).

Phase 0: Group A; Phase 0: Group B

177Lu-DOTA-JR11 (Phase I/II) DRUG

In the phase I/II part of the study: 3 cycles of 177Lu-DOTA-JR11 will be administered with an activity of 4.5-7.4 GBq. Two additional 177Lu-DOTA-JR11 treatment cycles can be performed if clinically indicated

Phase I/II

Eligibility Criteria

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

You may qualify if:

• Informed Consent as documented by signature
• Participants of any gender and of age \> 18 years
• Female participants capable of giving birth (who are not surgically sterilized or are less than 2 years in their menopause) must use a medically accepted contraceptive and must agree to use it during and till 3 months after the treatment. As acceptable contraceptive count sexual abstinence or double contraceptive methods: hormonal contraceptive (oral, transdermal, implants or injections) in combination with barrier methods (spiral, condom, diaphragm)
• Male participants must use medically accepted contraceptive during and till 3 months after treatment
• The participants' Karnofsky Performance Status must be ≥ 60
• The participants must be patients with a histologically or clinically confirmed (MRI + somatostatin receptor imaging) recurrent or progressive meningioma
• There must be no other standard therapeutic alternatives for the participants
• The participants tumour must be measurable according to RECIST v1.1 with a minimal diameter of 1.0 cm.
• The participants must have a confirmed expression of somatostatin receptor (SSTR) on 68Ga- DOTATOC positron emission computed tomography (PET)/CT scan
• Blood parameter criteria are:
• h) Leucocytes ≥ 3\*109/L i) Haemoglobin ≥ 80 g/L j) Thrombocytes ≥ 90\*109/L k) Estimated glomerular filtration rate ≥ 50 ml/min l) Albumin \> 25g/L m) alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP): ≤ 5 times upper standard value n) Bilirubin ≤ 2 times upper standard value

You may not qualify if:

• Known intolerance against 177Lu, DOTA, JR11, TOC or against one of the components of 177Lu-DOTA-JR11 or 177Lu-DOTATOC
• Ongoing infection at the screening visit or a serious infection in the past 4 weeks
• Administration of another investigational product in the last 60 days before Visit 1 Day 1
• Prior or planed administration of a therapeutic radio-pharmaceutical during 8 half-lives of the used radio-pharmaceutical's radionuclide, also during the ongoing study
• Pregnant or breastfeeding female patients. A pregnancy test will be performed in all women of child bearing potential.
• 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 might jeopardize the patient's safety or that would limit compliance with the objectives and assessments of the study. Any mental conditions which prevent the patient from understanding the type, extent and possible consequences of the study and/or an uncooperative attitude from the patient.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Swiss Cancer League: collaborator

Study Sites (1)

University Hospital Basel, Department of Neurosurgery

Basel, Canton of Basel-City, 4031, Switzerland

RECRUITING

MeSH Terms

Conditions

Meningioma; Neoplasms

Interventions

177Lu-DOTA-JR11; Crossing Over, Genetic; 177Lu-octreotide, DOTA(0)-Tyr(3)-

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Homologous Recombination; Recombination, Genetic; Genetic Phenomena

Study Officials

• Dominik Cordier, PD Dr. med.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Damian Wild, Prof. Dr. med.

CONTACT

+41 61 328 6683; damian.wild@usb.ch

Dominik Cordier, PD Dr. med.

CONTACT

+41 61 55 65 642; dominik.cordier@usb.ch

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a, two-step, cross-over, open-label phase 0 study comparing the therapeutic index of 177Lu-DOTA-JR11 and 177Lu-DOTATOC followed by a single-arm open-label Phase I/II study.

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: August 9, 2021
• Study Start: April 21, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 13, 2025

Record last verified: 2025-04

Locations

CH (1)