Treatment of Recurrent or Progressive Meningiomas With the Radiolabelled Somatostatin Antagonist 177Lu-Satoreotide (PROMENADE-Study)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Assessment of treatment safety (phase I/II) by number of AEs graded according to CTCAE v5.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Phase 0: Group A
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).
干预措施: 177Lu-DOTA-JR11 (Phase 0); Cycle 1 and Cycle 2 (cross-over) (Drug)
Phase 0: Group A
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).
干预措施: 177Lu-DOTATOC (Phase 0); Cycle 1 and Cycle 2 (cross-over), Cycle 3 and 4 (Drug)
Phase 0: Group B
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).
干预措施: 177Lu-DOTA-JR11 (Phase 0); Cycle 1 and Cycle 2 (cross-over) (Drug)
Phase 0: Group B
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).
干预措施: 177Lu-DOTATOC (Phase 0); Cycle 1 and Cycle 2 (cross-over), Cycle 3 and 4 (Drug)
Phase I/II
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
干预措施: 177Lu-DOTA-JR11 (Phase I/II) (Drug)
结局指标
主要结局
Assessment of treatment safety (phase I/II) by number of AEs graded according to CTCAE v5.0
时间窗: About 1 hour before infusion up to 41 - 45 days after infusion
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
Change in Tumour-to-dose limiting organ dose ratio T-to-kidney: Therapeutic Index (Phase 0)
时间窗: 24, 48 and 168 hours (+/- 30 min up to 24 hours)
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.
Change in Tumour-to-dose limiting organ dose ratio T-to-bone marrow: Therapeutic Index (Phase 0)
时间窗: 24, 48 and 168 hours (+/- 30 min up to 24 hours)
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.
次要结局
- Tumour absorbed dose (Gy) (Phase 0 and phase I/II)(up to 40 weeks)
- Organ absorbed dose (Gy) (Phase 0)(up to 40 weeks)
- Early onset toxicity (Phase 0)(up to 20 weeks)
- Evaluation radiation doses (Phase 0 and Phase II)(up to 40 weeks)
- Change in Quality of life (QoL) short form (SF) 36 questionnaire (Phase 0 and I/II)(From Screening up to 12 months after 3rd infusion)
- Change in Plasma Concentration [Cmax] of 177Lu-DOTA-JR11 in the human body (Phase I/II)(up to 50 weeks)
- Organ and tumour residence time (Phase 0)(up to 40 weeks)
- Tumour-to-remaining organ dose ratio (Phase 0)(up to 40 weeks)
- Change in visual parameters (Phase 0 and Phase I/II)(up to 60-70 weeks)
- Whole body and organ radiation doses (Phase I/II)(up to 60-70 weeks)