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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
196
Four administrations of 7.4 GBq (200 mCi) Lutetium\[177Lu\] Oxodotreotide Injection administered at 8 +/- 1-week intervals, which could be extended up to 16 weeks to accommodate resolving acute toxicity.
60 mg Octreotide LAR treatment was given to the participants every 4 weeks (i.m. injections) until the end of the study, unless the participant progressed or died.
Chinese PLA General Hospital
Progression Free Survival (PFS) assessed by BIRC
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).
Time frame: 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) assessed by investigator
Progression Free Survival (PFS) was defined as the time from randomization to documented investigator-assessed disease progression, or death due to any cause. If a participant had no investigator-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).
Time frame: 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
Objective Response Rate (ORR) was calculated as the proportion of patients with tumour size reduction (sum of partial responses (PR) and complete responses (CR)) and assessed by investigator according to RECIST 1.1.
Time frame: 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
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Beijing, Beijing Municipality, China
The First Afilliated Hospital of Fujian Medical University
Fuzhou, Fujian, China
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, China
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, China
The First Affiliated Hospital of Jinan University
Guangzhou, Guangdong, China
Henan Provincial People's Hospital
Zhengzhou, Henan, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei, China
Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
Wuhan, Hubei, China
Nanjing First Hospital
Nanjing, Jiangsu, China
...and 13 more locations
Objective Response Rate (ORR) assessed by BIRC
Objective Response Rate (ORR) was calculated as the proportion of patients with tumour size reduction (sum of partial responses (PR) and complete responses (CR)) assessed by BIRC according to RECIST 1.1.
Time frame: 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
The Duration of Response (DoR) was defined as the time from initially meeting the criteria for response (CR or PR) until the time of progression and assessed by investigator according to RECIST 1.1.
Time frame: 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
The Duration of Response (DoR) was defined as the time from initially meeting the criteria for response (CR or PR) until the time of progression assessed by BIRC according to RECIST v1.1.
Time frame: 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
Time to Tumour Progression (TTP) was defined as the time from randomization to progression assessed by investigator. It included patients who dropped out due to toxicity, but omitted patients who died without measured progression (censored to last follow-up date or death date).
Time frame: 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
Time to Tumour Progression (TTP) was defined as the time from randomization to progression assessed by BIRC. It included patients who dropped out due to toxicity, but omitted patients who died without measured progression (censored to last follow-up date or death date).
Time frame: 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
DCR is defined as the incidence of complete response, partial response and stable disease assessed by investigator according to RECIST v1.1.
Time frame: 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
DCR is defined as the incidence of complete response, partial response and stable disease assessed by BIRC according to RECIST v1.1.
Time frame: 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
20-month Progression-Free Survival rate was defined as the proportion of patients whose time from randomization to disease progression by BIRC according to RECIST v1.1 or death exceeds 20 months.
Time frame: 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
20-month Progression-Free Survival rate was defined as the proportion of patients whose time from randomization to disease progression by investigator according to RECIST v1.1 or death exceeds 20 months.
Time frame: 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)
Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause or the date of last contact (censored observation) prior to the date of the data cut-off, and during the entire study period (i.e. the treatment period plus follow-up).
Time frame: 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
The Quality of Life Questionnaire C30 (QLQ-C30) was developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess quality of life in cancer patients. It includes five function domains (physical, emotional, social, role, cognitive), eight symptoms (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnea, and appetite loss), as well as global health/quality-of-life and financial impact. Subjects respond on a four-point scale from "not at all" to "very much" for most items. Raw scores are linearly transformed so each score ranged a 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement).
Time frame: 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)
The Quality of Life GI Neuroendocrine Tumor survey (QLQ GINET21) contains a total of 21 items: four single-item assessments relating to muscle and/or bone pain (MBP), body image (BI), information (INF) and sexual functioning (SX), together with 17 items organized into five proposed scales: endocrine symptoms (ED; three items), GI symptoms (GI; five items), treatment-related symptoms (TR; three items), social functioning (SF) and disease-related worries (DRW; three items). The response format of the questionnaire is a four-point Likert scale. Responses are linearly transformed to a 0-100 scale using EORTC guidelines, with higher scores reflecting more severe symptoms.
Time frame: 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
The distribution of adverse events was done via the analysis of frequencies for Adverse Event (AEs), Serious Adverse Event (SAEs) and Deaths, through the monitoring of relevant clinical and laboratory safety parameters.
Time frame: From informed consent signature through study completion reached at final safety cutoff date，assessed up to approximately 60 months