Active, not recruiting
Phase 3
A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs
Condition(s) studied
Neuroendocrine Tumors
Investigational drug(s) / intervention(s)
Lutetium[177Lu] Oxodotreotide Injection: 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.
Octreotide LAR: 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.
Study 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.
Eligibility
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 outcome measure(s)
- Progression Free Survival (PFS) assessed by BIRC — 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).
Trial sites (23)
| Facility | City | Region | Status |
| Chinese PLA General Hospital |
Beijing |
Beijing Municipality |
|
| The First Afilliated Hospital of Fujian Medical University |
Fuzhou |
Fujian |
|
| The First Affiliated Hospital of Xiamen University |
Xiamen |
Fujian |
|
| The First Affiliated Hospital of Sun Yat-sen University |
Guangzhou |
Guangdong |
|
| The First Affiliated Hospital of Jinan University |
Guangzhou |
Guangdong |
|
| Henan Provincial People's Hospital |
Zhengzhou |
Henan |
|
| The First Affiliated Hospital of Zhengzhou University |
Zhengzhou |
Henan |
|
| Union Hospital Tongji Medical College Huazhong University of Science and Technology |
Wuhan |
Hubei |
|
| Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology |
Wuhan |
Hubei |
|
| Nanjing First Hospital |
Nanjing |
Jiangsu |
|
| The first hospital of Jilin University |
Changchun |
Jilin |
|
| The First Affiliated Hospital of AFMU |
Xi'an |
Shaanxi |
|
| The First Affiliated Hospital of Xi'an Jiaotong University |
Xi'an |
Shaanxi |
|
| Qilu Hospital of Shandong University |
Jinan |
Shandong |
|
| Fudan University Shanghai Cancer Center |
Shanghai |
Shanghai Municipality |
|
| Zhongshan Hospital, Fudan University |
Shanghai |
Shanghai Municipality |
|
| The First Affiliated Hospital of Shanxi Medical University |
Taiyuan |
Shanxi |
|
| West China Hospital of Sichuan University |
Chengdu |
Sichuan |
|
| Affiliated Hospital of Southwest Medical University |
Luzhou |
Sichuan |
|
| Mianyang Central Hospital |
Mianyang |
Sichuan |
|
| Tianjin Medical University Cancer Institute & Hospital |
Tianjin |
Tianjin Municipality |
|
| The First Affiliated Hospital, Zhejiang University School of Medicine |
Hangzhou |
Zhejiang |
|
| Zhejiang Cancer Hospital |
Hangzhou |
Zhejiang |
|
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