2024-518325-15-00招募中3 期
A phase III multi-center, randomized, open-label study to evaluate the efficacy and safety of [177Lu]Lu-DOTA-TATE in patients newly diagnosed with Grade 1 and Grade 2 (Ki-67 <10%) advanced GEP-NET with high disease burden (NETTER-3)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 99
- 试验地点
- 36
- 主要终点
- PFS, defined as the time from randomization to the first occurrence of progression (centrally assessed by Blinded Independent Review Committee (BIRC) according to RECIST v1.1) or death due to any cause
研究概览
简要总结
To demonstrate that [177Lu]Lu-DOTA-TATE plus octreotide LAR is superior to active comparator in delaying the time-to-first occurrence of progression or death (PFS) as first line treatment.
入排标准
- 年龄范围
- 0 years 至 65+ years（65+ Years, 0-17 Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Presence of metastasized or locally advanced, unresectable (curative intent), histologically proven, well differentiated G1 or G2 (Ki-67 <10%) GEP-NET diagnosed within 6 months prior to screening.
- •Participants with high disease burden in the Investigator's opinion. Following criteria should be used as the guiding principle for determining high disease burden: • Primary tumor or a metastatic lesion > 4 cm • More than one tumor or metastatic lesions measuring > 2 cm • Elevated alkaline phosphatase > 2.5 X upper limit of normal (ULN) • Presence of bone metastasis • Presence of peritoneal metastasis • Symptoms due to tumor volume such as pain, fatigue, weight loss, anorexia etc. • Symptoms due to hormone excess requiring active management Additionally, participants who, in the Investigator's opinion, have high disease burden due to their disease characteristics not specified above could also be considered eligible. The clinical characteristics of the disease must be clearly recorded in the electronic case report form.
- •Participants ≥ 12 years of age. For Germany, Hungary, The Netherlands and Poland, only adult participants ≥ 18 years of age will be enrolled.
- •Radioligand imaging (RLI) SSTR uptake on all target lesions (defined by RECIST v1.1 criteria) at least as high as normal liver uptake, assessed within 3 months prior to randomization. Any of the RLI modalities such as, [68Ga]Ga-DOTA-TOC PET/CT or PET/MRI, [68Ga]Ga-DOTA-TATE PET/CT or PET/MRI, [64Cu]Cu-DOTA-TATE PET/CT or PET/MRI, somatostatin receptor scintigraphy (SRS) (planar and/or SPECT/CT) with [111In]In-pentetreotide, or SRS (planar and/or SPECT/CT) with [99mTc]Tc-octreotide, can be used as per local practice.
- •Adequate bone marrow and organ function as defined by the following laboratory values prior to receiving the first study treatment: a. White blood cells (WBCs) ≥ 2 x 109/L* b. Platelet count ≥ 75 x 109/L* c. Hemoglobin ≥ 8 g/dL* d. Creatinine clearance > 40 mL/min calculated by the Cockcroft Gault method e. Total bilirubin ≤ 3 x ULN f. Potassium within normal limits. Potassium level of up to 6.0 millimoles per liter (mmol/L) is acceptable at study entry if associated with creatinine clearance withinr normal limits calculated using Cockcroft-Gault formula. Mild decrease (grade 1) below lower limit of normal (LLN) is acceptable at study entry if considered not clinically significant by Investigator. See details regarding potassium assessment and Lysine – Arginine amino acid solution administration in Section 8.4.
- •No platelet transfusion packed red cell transfusion, or granulocyte-colony stimulating factor (G-CSF) will be allowed during screening after ICF signature. Transfusion for the sole purpose of making a participant eligible for the study inclusion is not allowed.
- •ECOG performance status 0-
- •Presence of at least 1 measurable site of disease
排除标准
- •Prior administration of a therapeutic radiopharmaceutical for GEP-NET at any time prior to randomization in the study.
- •Active severe urinary incontinence, severe voiding dysfunction, or urinary obstruction requiring an indwelling/condom catheter that, in the judgment of the Investigator, could prevent adhering to radiation safety instructions.
- •Any previous therapy with interferons, mTOR-inhibitors, chemotherapy or other systemic therapies (except SSAs; please refer to exclusion criteria # 3 for further details) of GEP-NET. If as per Investigator opinion a participant is a candidate for such therapies, such participant must not be enrolled.
- •Participant who received more than 4 cycles of prior SSA (e.g., octreotide LAR) are not eligible. In addition, any participant receiving treatment with short-acting octreotide, which cannot be interrupted for 24 h before the administration of [177Lu]Lu-DOTA-TATE, or any participant receiving treatment with SSAs, which cannot be interrupted for at least 4 weeks before the administration of [177Lu]Lu-DOTA-TATE.
- •Documented RECIST v1.1 progression during previous SSA treatments for the current GEP-NET at any time prior to randomization.
- •Any previous radioembolization, chemoembolization and radiofrequency ablation for GEP-NET
- •Any major surgery within 12 weeks prior to randomization in the study.
- •Known brain metastases.
- •Participant with known intolerance to CT scans with i.v. contrast due to allergic reaction or renal insufficiency. If such a participant can be imaged with MRI, then the participant would not be excluded.
- •Hypersensitivity to any somatostatin analogues, to the Investigational Medicinal Products (IMPs) active substance or to any of the excipients.
结局指标
主要结局
PFS, defined as the time from randomization to the first occurrence of progression (centrally assessed by Blinded Independent Review Committee (BIRC) according to RECIST v1.1) or death due to any cause
PFS, defined as the time from randomization to the first occurrence of progression (centrally assessed by Blinded Independent Review Committee (BIRC) according to RECIST v1.1) or death due to any cause
次要结局
- Time to deterioration (by an absolute change of at least 15%), defined as the time from randomization to the first occurrence of deterioration compared to baseline scores or death from any cause for each of the following domains (tested separately) of EORTC QLQ-GI.NET21 [gastrointestinal scale (GI scale)] and EORTC QLQ-C30 questionnaires (fatigue, diarrhea, and global health scale).
- PFS, defined as the time from randomization to the first occurrence of progression (Investigator assessed according to RECIST v1.1) or death due to any cause.
- Objective response rate (ORR): Rate of participants with best overall response (BOR) of partial response (PR) or complete response (CR) as per RECIST v1.1 (both Investigator and centrally assessed by BIRC).
- Disease control rate (DCR): Rate of participants with BOR of PR, CR or stable disease (SD) as per RECIST v1.1 (both Investigator and centrally assessed by BIRC).
- DOR: The time from initially meeting the criteria for response (CR or PR) until the time of progression according to RECIST v1.1 or death due to underlying disease only.
- Incidence and severity of adverse events (AEs) and serious adverse event (SAEs), changes in laboratory values, vital signs and ECGs. Tolerability: Dose interruptions, discontinuations, and reductions.
- OS: Time from the randomization date until the date of death due to any cause.
- • TTD (using the same definition as for key secondary endpoints) for EORTC QLQ-G.I.NET21 and EORTC QLQ-C30 domains not included among key secondary endpoints • Absolute change from baseline in EORTC QLQ-G.I.NET21 and EORTC QLQ-C30 domains. • Absolute change from baseline in the EQ-5D-5L index at each timepoint.
- Absorbed radiation dose in selected organs, tumor lesions and total body.
- PK parameters (Area Under Curve (AUC), clearance, distribution volume, half-life) from [177Lu]Lu-DOTA-TATE blood radioactivity data.
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG
研究点 (36)
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