Clinical trial NCT04997317: Treatment of Recurrent or Progressive Meningiomas With the Radiolabelled Somatostatin Antagonist 177Lu-satoreotide
Official title: Treatment of Recurrent or Progressive Meningiomas With the Radiolabelled Somatostatin Antagonist 177Lu-Satoreotide (PROMENADE-Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss Cancer League
First posted: 2021-08-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: The somatostatin receptor subtype 2 (sstr2) has been identifies as a peptide hormone receptor that is highly expressed in 70 - 100% of meningiomas representing an attractive target for so called "theranostic" applications combining molecular imaging and targeted radionuclide therapy with radiolabelled somatostatin analogues.The newly developed radiolabelled somatostatin antagonist 177Lu-DOTA-JR11 has been shown to exert a high binding affinity to sstr2 suggesting a higher efficacy in the treatment of advanced meningiomas than the currently available somatostatin analogues (e.g. 177Lu-DOTATOC, 177Lu-DOTATATE).Therefore, the hypothesis has been postulated that 177LuDOTA-JR11 has an improved therapeutic index (tumour-to-dose limiting organ dose ratios) compared to 177Lu-DOTATOC, and that it can be safely used for PRRT in patients with advanced, recurrent or progressive meningiomas. The aim of this 2-step Phase 0 / Phase I/II study is to a) evaluate in the same meningioma patients the therapeutic index (tumour-to-dose limiting organ dose ratios) of 177Lu-DOTA-JR11 in comparison to 177Lu-DOTATOC and b) based on the previous results, to evaluate safety and preliminary efficacy of PRRT with 177Lu-DOTA-JR11.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Any extensive Radiotherapy involving bone marrow over the last 3 months before inclusion to the study
* Chemotherapy in the last 2 months before inclusion
* 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.

Primary outcomes:
measure: Change in Tumour-to-dose limiting organ dose ratio T-to-bone marrow: Therapeutic Index (Phase 0)
timeFrame: 24, 48 and 168 hours (+/- 30 min up to 24 hours)
measure: Change in Tumour-to-dose limiting organ dose ratio T-to-kidney: Therapeutic Index (Phase 0)
timeFrame: 24, 48 and 168 hours (+/- 30 min up to 24 hours)
measure: Assessment of treatment safety (phase I/II) by number of AEs graded according to CTCAE v5.0
timeFrame: About 1 hour before infusion up to 41 - 45 days after infusion
Secondary outcomes:
measure: Tumour absorbed dose (Gy) (Phase 0 and phase I/II)
timeFrame: up to 40 weeks
measure: Organ absorbed dose (Gy) (Phase 0)
timeFrame: up to 40 weeks
measure: Organ and tumour residence time (Phase 0)
timeFrame: up to 40 weeks
measure: Tumour-to-remaining organ dose ratio (Phase 0)
timeFrame: up to 40 weeks
measure: Evaluation radiation doses (Phase 0 and Phase II)
timeFrame: up to 40 weeks
measure: Early onset toxicity (Phase 0)
timeFrame: up to 20 weeks
measure: Change in Quality of life (QoL) short form (SF) 36 questionnaire (Phase 0 and I/II)
timeFrame: From Screening up to 12 months after 3rd infusion
measure: Change in visual parameters (Phase 0 and Phase I/II)
timeFrame: up to 60-70 weeks
measure: Change in Plasma Concentration [Cmax] of 177Lu-DOTA-JR11 in the human body (Phase I/II)
timeFrame: up to 50 weeks
measure: Whole body and organ radiation doses (Phase I/II)
timeFrame: up to 60-70 weeks
Other outcomes:
measure: Assessement of Progression-Free Survival (PFS) (Phase 0 and I/II))
timeFrame: up to 12 months
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Department of Neurosurgery
state: Basel-Stadt
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Dominik Cordier, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: