A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With Inoperable, Progressive, Well Differentiated, Somatostatin Receptor Positive Gastroenteropancreatic Neuroendocrine Tumours
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 196
- 试验地点
- 23
- 主要终点
- Progression Free Survival (PFS) assessed by BIRC
研究概览
简要总结
This was a multicenter, stratified, open, randomized, comparator-controlled, parallel-group phase III study comparing treatment with Lutetium[177Lu] Oxodotreotide Injection to high dose (60 mg) Octreotide LAR in patients with unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours.
详细描述
After the screening period, participants who signed the ICF and were eligible for the study in accordance with the entry criteria were randomly assigned to treatment either Lutetium[177Lu] Oxodotreotide Injection or Octreotide LAR. Participant randomization was performed according to a centralized permuted block randomization scheme with a balanced ratio (1:1) between the 2 treatment groups, stratified by primary site of tumor (pancreatic or non-pancreatic), NET pathological grading (G1 or G2) and by the length of time that a participant was on a constant dose of Octreotide (=< 6 versus > 6 months). Objective tumor assessment in both groups was performed every 12+/-1 weeks from the randomization date according to RECIST Criteria until progression was centrally confirmed: any participants with progressive disease ceased the treatment/assessment period and proceeded to the long-term follow-up period for evaluation of survival and long-term safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Ability to understand and willingness to sign a written informed consent document.
- •Aged 18 years or older.
- •Histopathologically confirmed low and moderate grade (G1 or G2) unresectable locally advanced or metastatic GEP-NET (based on the fifth edition of the WHO classification and grading criteria for neuroendocrine tumors of the digestive system in 2019, to be centrally confirmed).
- •Previously received fixed-dose Octreotide LAR (20-30 mg/3-4 weeks) for at least 12 weeks of continuous treatment with disease progression.
- •Presence of disease progression prior to randomization (time point of disease progression limited to 1 year prior to randomization and no other antitumor therapy received after progression).
- •Presence of at least 1 measurable site of disease (based on RECIST 1.1).
- •All target lesions (based on RECIST 1.1) at baseline must be confirmed as somatostatin receptor positive by 68Ga-Dotatate PET/CT .
- •ECOG score of 0 or
- •Subjects of childbearing potential voluntarily use an effective method of contraception, such as condoms, oral or injectable contraceptives, IUDs, etc., during treatment and within 4 months (men) or 7 months (women) of the last use of the trial drug.
排除标准
- •Serum creatinine >150 μmol/L (1.7 mg/dL) or creatinine clearance <50 ml/min (Cockcroft Gault formula).
- •Hemoglobin <80g/L, or white blood cell count <2.0×10^9/L, or platelets <75×10^9/L.
- •Serum total bilirubin > 3 × upper limit of normal (ULN).
- •Serum albumin <30g/L.
- •alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5×ULN.
- •international normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 x ULN.
- •Positive human immunodeficiency virus (HIV) antibody.
- •Positive for hepatitis B virus (HBV) surface antigen (HBsAg) and positive for HBV DNA (≥1×10^4 copies/ml or judged positive by research center criteria), or positive for hepatitis C virus (HCV) antibodies.
- •Pregnant or lactating females.
- •Received peptide receptor radionuclide therapy(PRRT) prior to randomization.
- •Received Octreotide LAR at a dose strength >30 mg/3-4 weeks (increasing dose or frequency) within 12 weeks prior to randomization.
- •Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of Lutetium[177Lu] Oxodotreotide Injection, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 6 weeks before the administration of Lutetium[177Lu] Oxodotreotide Injection.
- •Received systemic antitumor therapy such as targeted therapy, immunotherapy, antitumor herbal therapy, chemotherapy within 4 weeks prior to randomization.
- •Participated in other drug clinical trials within 4 weeks prior to randomization and received treatment with the corresponding trial drug.
- •Received the following treatments within 12 weeks prior to randomization, including but not limited to surgery (except biopsy), radical radiotherapy, hepatic artery interventional embolization, cryoablation of liver metastases, or radiofrequency ablation.
- •Received external beam radiation therapy for bone metastases within 2 weeks prior to randomization
- •Toxicity of prior antitumor therapy has not returned to ≤ grade 1 levels (except for alopecia)
- •Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrollment in the study.
- •Uncontrolled congestive heart failure, including baseline left ventricular ejection fraction (LVEF) <50%.
- •uncontrolled diabetes mellitus, including baseline fasting glucose > 2 x ULN.
- •Any clinically significant active infection.
- •Known other malignancies (except for those without recurrence within 5 years after adequate treatment)
- •Known hypersensitivity to Lutetium[177Lu] Oxodotreotide Injection or oxytetracycline acetate microsphere components and their excipients.
- •Known to be unsuitable for enhanced CT or MRI contrast imaging due to allergic reaction or renal insufficiency.
- •Any other disease, mental status or surgical condition that is uncontrolled, may interfere with study completion (including poor compliance) or is inappropriate for the use of the investigational drug.
- •Other treatment options (e.g., chemotherapy, targeted therapy) that, in the opinion of the investigator, are more appropriate for the patient than the treatment provided in the study based on the patient's disease characteristics, i.e., the investigational drug is not the best therapeutic agent for clinical practice.
研究组 & 干预措施
Lutetium[177Lu] Oxodotreotide Injection
Treatment consisted of a cumulative administered radioactivity of 29.6 Giga Becquerel (GBq) (800 mCi) Lutetium[177Lu] Oxodotreotide Injection: Four administrations of 7.4 GBq (200 mCi).
Concomitant amino acids were given with each administration for kidney protection.
Lutetium[177Lu] Oxodotreotide Injection was administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.
In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, Octreotide s.c. rescue injections were allowed.
干预措施: Lutetium[177Lu] Oxodotreotide Injection (Drug)
Octreotide LAR
60 mg Octreotide LAR treatment every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.
In case participants experienced clinical symptoms (i.e. diarrhoea and flushing) associated with their carcinoid tumours, s.c. Octreotide rescue injections were allowed.
干预措施: Octreotide LAR (Drug)
结局指标
主要结局
Progression Free Survival (PFS) assessed by BIRC
时间窗: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months
Progression Free Survival (PFS) was defined as the time from randomization to documented centrally assessed disease progression, as evaluated by the Blinded Independent Review Committee (BIRC), or death due to any cause. If a participant had no centrally assessed progression and had not died at the time of the primary endpoint analysis, the participant was regarded as censored in the context of a time to event analysis at the date of last evaluable tumor assessment. Disease progression was determined by objective tumor response status using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1).
次要结局
- Progression Free Survival (PFS) assessed by investigator(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Objective Response Rate (ORR) assessed by investigator(From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Objective Response Rate (ORR) assessed by BIRC(From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Duration of Response (DoR) assessed by investigator(From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Duration of Response (DoR) assessed by BIRC(From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Time to Tumour Progression (TTP) assessed by investigator(From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Time to Tumour Progression (TTP) assessed by BIRC(From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Disease Control Rate (DCR) assessed by investigator(From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Disease Control Rate (DCR) assessed by BIRC(From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- 20-month Progression-Free Survival rate assessed by BIRC(From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- 20-month Progression-Free Survival rate assessed by investigator(From date of randomization until date of progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Overall Survival (OS)(From date of randomization until date of death from any cause up to final safety cut-off date reached，assessed up to approximately 60 months)
- Change From Baseline in the EORTC QLQ-C30 Questionnaire(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Change From Baseline in the EORTC Quality of Life Questionnaire - Neuroendocrine Carcinoid Module (EORTC QLQ-GINET21)(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first until Primary Analysis cutoff date reached，assessed up to approximately 34 months)
- Number of Participants With Adverse Events(From informed consent signature through study completion reached at final safety cutoff date，assessed up to approximately 60 months)