NCT02592707终止1 期
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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Ipsen
- 入组人数
- 40
- 试验地点
- 9
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLT)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Written informed consent.
- •Patients of either gender, aged ≥ 18 years.
- •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.).
- •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.
- •Karnofsky performance score ≥
- •Life expectancy of at least 6 months.
- •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
- •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.
- •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.
- •Measurable disease based on RECIST v1.
- •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.
- •Calculated GFR ≥ 55 mL/min.
- •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)
排除标准
- •Known hypersensitivity to 177Lu, to DOTA, to JR11 or to any of the excipients of 177Lu-OPS
- •Any previous peptide receptor radionuclide therapy (PRRT).
- •Diagnosis of thymic NET.
- •Presence of active infection at screening or history of serious infection within the previous 6 weeks.
- •Administration of any other investigational medicinal product within 60 days prior to entry.
- •Prior or planned administration of a therapeutic radiopharmaceutical within 8 half-lives of the radionuclide including any time during the current study.
- •Any extensive radiotherapy ≤ 3 months before enrolment.
- •Chemotherapy ≤ 3 months before enrolment.
- •Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject at high risk of renal toxicity during the study as assessed by the investigator.
- •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).
- •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.
- •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
- •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.
研究组 & 干预措施
177Lu-IPN01072
Experimental
177Lu-IPN01072 administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles)
干预措施: Satoreotide tetraxetan (Drug)
177Lu-IPN01072
Experimental
177Lu-IPN01072 administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles)
干预措施: Amino acid solution (Other)
177Lu-IPN01072
Experimental
177Lu-IPN01072 administered in 3 cycles at intervals of 8 weeks (+ up to 2 additional optional cycles)
干预措施: Antiemetic (Other)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLT)
时间窗: From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks.
DLTs were defined as study medication-related AEs with a severity of Grade 3 or higher are considered DLT, with the exception of hair loss, lymphopenia, nonfebrile neutropenia lasting \<4 weeks and thrombocytopenia lasting \<4 weeks.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
时间窗: From the start of the first study medication (Cycle 1 Day 1) up to 6 months after the last dose of study medication, maximum of 33 months
AE is defined as any untoward medical occurrence in a subject or clinical trial subject administered a medicinal product, which did not necessarily have a causal relationship with this treatment. A serious AE (SAE) was classified as any untoward medical occurrence that at any dose results in death; AE was life threatening; required inpatient hospitalization or prolonged existing hospitalization; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect; was an important medical event that may not result in death. TEAEs are defined as AEs that developed or worsened after start of treatment.
次要结局
- Ae (0-48h) of IPN01072 in Cycle 1(0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 of Part B)
- Maximal Uptake (%) of 177Lu-IPN01072 in Blood in Cycle 1(Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1)
- Cumulative Amount of Lu-177 Radioactivity Excreted Into the Urine (0 to 48 Hours) [Ae (0-48h)] in Cycle 1(0 to 6 hours, 6 to 24 hours, 24 to 48 hours post-infusion in Cycle 1 of Part A; 0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 of Part B.)
- Time to Reach Maximum Plasma Concentration (Tmax) of IPN01072 in Cycle 1(Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1)
- AUC From Time Zero to Infinity (AUCinf) of IPN01072 in Cycle 1(Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1)
- Apparent Volume of Distribution During Terminal Phase (Vz) of IPN01072 in Cycle 1(Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1)
- Maximum Uptake (%) of 177Lu-IPN01072 at Target Lesions and Discernible Organs in Cycle 1(4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1)
- Fraction of IPN01072 Excreted Into the Urine (Fe) in Cycle 1(0 to 4 hours, 4 to 24 hours, 24 to 48 hours in Cycle 1 in Part B)
- Area Under the Concentration Time Curve (AUC) of 177Lu-IPN01072 in Discernible Organs in Cycle 1(4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1)
- AUC of 177Lu-IPN01072 in Blood in Cycle 1(Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1)
- Highest Absorbed Dose of 177LU-IPN01072 to Each Discernible Organ in Cycle 1(4, 24, 48, 72 to 96 and 144 to 168 hours post infusion in Cycle 1)
- Terminal Half-Life (T1/2) of Radioactivity Concentrations of the Radiopharmaceutical in Blood in Cycle 1(Pre-infusion (Baseline), 5 and 30 minutes, 1, 4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1)
- Cumulative Absorbed Organ Doses of 177Lu-IPN01072 in Cycles 1 and 3(4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycles 1 and 3)
- Maximum Observed Plasma Concentration (Cmax) of IPN01072 in Cycle 1(Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1)
- T1/2 of IPN01072 in Cycle 1(Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1)
- Best Overall Response(From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.)
- Change From Baseline in Quality of Life (QoL) Questionnaire (QLQ)-C30 at EOCT Visit(Baseline (Day 1) and EOCT visit (30 months))
- Change From Baseline in QLQ Gastro-intestinal. Neuroendocrine Tumour (GI.NET)21 at EOCT Visit(Baseline (Day 1) and EOCT visit (30 months))
- Specific Absorbed Dose Per Organ and Lesions of 177Lu-IPN01072 in Cycle 1(4, 24, 48, 72 to 96 hours, 144 to 168 hours post infusion in Cycle 1)
- Apparent Total Plasma Clearance of IPN01072 (Total CL) in Cycle 1(Pre-infusion (Baseline) and 5 minutes, 30 minutes, 60 minutes, 4 hours, 6 hours, 8 hours, 24 hours, 48 hours after the end of the infusion in Cycle 1)
- Overall Response Rate (ORR)(From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.)
- Disease Control Rate (DCR)(From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.)
- Progression Free Survival (PFS)(From the start of the first study medication (Cycle 1 Day 1) up to 2 years after the EOCT/death or lost to follow-up, maximum of 59 months.)
研究者
研究点 (9)
Loading locations...
相似试验
已完成
1 期
A Study to Evaluate ICP-022 in Patients With R/R Mantle Cell Lymphoma (MCL)Mantle Cell LymphomaNCT03494179Beijing InnoCare Pharma Tech Co., Ltd.106
已完成
2 期
A Study to Evaluate ICP-022 in Patients With R/R Marginal Zone Lymphoma (MZL)MZLNCT03797456Beijing InnoCare Pharma Tech Co., Ltd.111
终止
1 期
Safety and Efficacy of MIW815 (ADU-S100) +/- Ipilimumab in Patients With Advanced/Metastatic Solid Tumors or LymphomasAdvanced/Metastatic Solid Tumors or LymphomasNCT02675439Chinook Therapeutics, Inc. (formerly Aduro)47
终止
1 期
Study of the Safety and Efficacy of MIW815 With PDR001 in Patients With Advanced/Metastatic Solid Tumors or LymphomasSolid Tumors and LymphomasNCT03172936Novartis Pharmaceuticals106
已完成
1 期
Phase I Study on VEGF Vaccination in Metastatic Solid TumorsMetastatic CancerNCT02237638Amsterdam UMC, location VUmc30