Clinical trial NCT05459844: A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Neuroendocrine Tumors
Keywords: Neuroendocrine tumour
177Lu-Dota0-Tyr3-octreotate
Lead sponsor: Sinotau Pharmaceutical Group
Sponsor class: INDUSTRY
First posted: 2022-07-15
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Ability to understand and willingness to sign a written informed consent document.
2. Aged 18 years or older.
3. 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).
4. Previously received fixed-dose Octreotide LAR (20-30 mg/3-4 weeks) for at least 12 weeks of continuous treatment with disease progression.
5. 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).
6. Presence of at least 1 measurable site of disease (based on RECIST 1.1).
7. All target lesions (based on RECIST 1.1) at baseline must be confirmed as somatostatin receptor positive by 68Ga-Dotatate PET/CT .
8. ECOG score of 0 or 1.
9. 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.

Exclusion Criteria:

1. Serum creatinine \>150 μmol/L (1.7 mg/dL) or creatinine clearance \<50 ml/min (Cockcroft Gault formula).
2. Hemoglobin \<80g/L, or white blood cell count \<2.0×10\^9/L, or platelets \<75×10\^9/L.
3. Serum total bilirubin \> 3 × upper limit of normal (ULN).
4. Serum albumin \<30g/L.
5. alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5×ULN.
6. international normalized ratio (INR) \> 1.5 or partially activated prothrombin time (APTT) \> 1.5 x ULN.
7. Positive human immunodeficiency virus (HIV) antibody.
8. 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.
9. Pregnant or lactating females.
10. Received peptide receptor radionuclide therapy(PRRT) prior to randomization.
11. Received Octreotide LAR at a dose strength \>30 mg/3-4 weeks (increasing dose or frequency) within 12 weeks prior to randomization.
12. 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.
13. Received systemic antitumor therapy such as targeted therapy, immunotherapy, antitumor herbal therapy, chemotherapy within 4 weeks prior to randomization.
14. Participated in other drug clinical trials within 4 weeks prior to randomization and received treatment with the corresponding trial drug.
15. 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.
16. Received external beam radiation therapy for bone metastases within 2 weeks prior to randomization
17. Toxicity of prior antitumor therapy has not returned to ≤ grade 1 levels (except for alopecia)
18. Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrollment in the study.
19. Uncontrolled congestive heart failure, including baseline left ventricular ejection fraction (LVEF) \<50%.
20. uncontrolled diabetes mellitus, including baseline fasting glucose \> 2 x ULN.
21. Any clinically significant active infection.
22. Known other malignancies (except for those without recurrence within 5 years after adequate treatment)
23. Known hypersensitivity to Lutetium\[177Lu\] Oxodotreotide Injection or oxytetracycline acetate microsphere components and their excipients.
24. Known to be unsuitable for enhanced CT or MRI contrast imaging due to allergic reaction or renal insufficiency.
25. 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.
26. 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.

Primary outcomes:
measure: Progression Free Survival (PFS) assessed by BIRC
timeFrame: 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
Secondary outcomes:
measure: Progression Free Survival (PFS) assessed by investigator
timeFrame: 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
measure: Objective Response Rate (ORR) assessed by investigator
timeFrame: 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
measure: Objective Response Rate (ORR) assessed by BIRC
timeFrame: 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
measure: Duration of Response (DoR) assessed by investigator
timeFrame: 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
measure: Duration of Response (DoR) assessed by BIRC
timeFrame: 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
measure: Time to Tumour Progression (TTP) assessed by investigator
timeFrame: 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
measure: Time to Tumour Progression (TTP) assessed by BIRC
timeFrame: 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
measure: Disease Control Rate (DCR) assessed by investigator
timeFrame: 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
measure: Disease Control Rate (DCR) assessed by BIRC
timeFrame: 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
measure: 20-month Progression-Free Survival rate assessed by BIRC
timeFrame: 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
measure: 20-month Progression-Free Survival rate assessed by investigator
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: 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
measure: Change From Baseline in the EORTC QLQ-C30 Questionnaire
timeFrame: 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
measure: Change From Baseline in the EORTC Quality of Life Questionnaire - Neuroendocrine Carcinoid Module (EORTC QLQ-GINET21)
timeFrame: 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
measure: Number of Participants With Adverse Events
timeFrame: From informed consent signature through study completion reached at final safety cutoff date，assessed up to approximately 60 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Fuzhou
country: China
facility: The First Afilliated Hospital of Fujian Medical University
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
state: Hubei
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Changchun
country: China
facility: The first hospital of Jilin University
state: Jilin
city: Xi'an
country: China
facility: The First Affiliated Hospital of AFMU
state: Shaanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
city: Taiyuan
country: China
facility: The First Affiliated Hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Luzhou
country: China
facility: Affiliated Hospital of Southwest Medical University
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Chinese PLA General Hospital
name: Jianming Xu
role: PRINCIPAL_INVESTIGATOR
References: