A Clinical Study of Lutetium[177Lu] Oxodotreotide Injection in Patients With Advanced Neuroendocrine Neoplasms
A Clinical Study to Evaluate the Safety and Efficacy of Lutetium[177Lu] Oxodotreotide Injection in Patients With Advanced Somatostatin Receptor Positive Neuroendocrine Neoplasms
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study consists of two parts, the exploratory study (Part 1) and the pivotal study (Part 2).
In both parts, participants who signs Informed consent form (ICF) and is eligible for the study will be enrolled. Participants will receive 7.4GBq (200mCi) Lutetium [177Lu] Oxyoctreotide every 8 weeks. The objective tumor response will be assessed every 12 weeks from the time of the first dose according to RECIST 1.1 until disease progression.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Shan Zhang
- Phone Number: +86-010-52805710
- Email: zhangshan@sinotau.com
Study Locations
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Shanghai Municipality
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Shanghai, Shanghai Municipality, China
- Recruiting
- Fudan University Shanghai Cancer Center
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Contact:
- Jie Chen, MD
- Phone Number: +86-021-68070288
- Email: Chen0jie@hotmail.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Subjects who have been fully informed of this study and have voluntarily signed the Informed Consent Form (ICF).
- Age ≥12 years; subjects aged 12-17 years must have a body weight ≥40kg. Age eligibility must be met at the time of signing the ICF.
- Histologically confirmed, unresectable locally advanced or metastatic neuroendocrine neoplasms (NENs) [excluding well-differentiated (G1 and G2) gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and neuroendocrine carcinomas (NECs)]. The target population mainly includes:
(1)Grade 3 (G3) GEP-NET with Ki-67 index ≤ 55% (2)Other non-gastroenteropancreatic originated NEN, including pulmonary/thymic NEN, primary NEN of other sites, and NEN of unknown primary origin (3)Pheochromocytoma and paraganglioma (PPGL) Note: Histopathological specimens collected within 3 years prior to the first study drug administration are acceptable, provided that investigators confirm they can represent the pathological status at enrollment; otherwise, fresh specimens shall be collected.
4. Patients who have failed prior optimal available treatment, are intolerant to optimal available treatment, or have no access to optimal available treatment, with no restriction on the number of prior treatment lines.
Note: Optimal available treatment is determined by investigators based on individual subject conditions, including chemotherapy, targeted therapy, biologic therapy, etc.
5.Have documented disease progression within 1 year prior to the first study drug administration, and have not received any other systemic anti-tumor therapy after disease progression.
6.Have at least one measurable lesion at baseline per RECIST 1.1 criteria. 7. All baseline target lesions (per RECIST 1.1) must be confirmed as somatostatin receptor-positive via ⁶⁸Ga-Dotatate PET/CT.
Notes:
- ⁶⁸Ga-Dotatate PET/CT images obtained within 24 weeks before the first drug administration are acceptable if investigators verify they can reflect the somatostatin receptor status at enrollment;
- Somatostatin receptor positivity is defined as lesion uptake higher than normal liver uptake;
- Subjects with any target lesion confirmed somatostatin receptor-negative by ⁶⁸Ga-Dotatate PET/CT shall be excluded.
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 at baseline.
9. Subjects of childbearing potential must voluntarily use effective contraceptive methods throughout the treatment period and for 4 months (male) or 7 months (female) after the last dose of investigational product, such as condoms, oral/injectable contraceptives, intrauterine devices, etc.
Exclusion Criteria
- Serum creatinine > 150 μmol/L (1.7 mg/dL) or creatinine clearance rate < 50 mL/min (calculated by Cockcroft-Gault formula).
- Hemoglobin < 100 g/L, white blood cell count < 2.0×10⁹/L, or platelet count < 100×10⁹/L.
- Total serum bilirubin > 3 times the upper limit of normal (ULN).
- Serum albumin < 30 g/L.
- Alanine transaminase (ALT) or aspartate transaminase (AST) > 2.5×ULN.
- International Normalized Ratio (INR) > 1.5 or activated partial thromboplastin time (APTT) > 1.5×ULN.
- Positive human immunodeficiency virus (HIV) antibody.
- Positive hepatitis B surface antigen (HBsAg) combined with positive HBV-DNA (≥1×10⁴ copies/mL or confirmed positive per local study center criteria); or positive hepatitis C virus (HCV) antibody combined with positive HCV-RNA (≥1×10³ copies/mL).
- Pregnant or breastfeeding females.
- Prior history of peptide receptor radionuclide therapy (PRRT).
Subjects receiving short-acting octreotide who cannot discontinue it within 24 hours before and after administration of Lutetium-177 Oxotreotide Injection; or subjects receiving octreotide acetate microspheres who cannot stop the treatment within 6 weeks prior to the first dose of Lutetium-177 Oxotreotide Injection.
Note: Further evaluation is required for subjects receiving other somatostatin analog (SSA) treatments.
- Received systemic anti-tumor therapies including targeted therapy, immunotherapy, anti-tumor traditional Chinese medicine therapy or chemotherapy within 4 weeks before the first study drug administration.
- Enrolled in other clinical trials and received investigational drugs within 4 weeks prior to the first dose.
- Received local anti-tumor treatments such as surgery (excluding biopsy), radical radiotherapy, hepatic arterial chemoembolization, cryoablation or radiofrequency ablation for liver metastases within 4 weeks before the first dose.
- Received palliative radiotherapy for bone metastases within 2 weeks prior to the first dose.
- Toxicities from previous anti-tumor therapies have not recovered to Grade 1 or lower (alopecia excluded).
- Confirmed brain metastases (excluding those stabilized for at least 24 weeks before the first administration).
- Uncontrolled congestive heart failure, including baseline left ventricular ejection fraction (LVEF) < 50%.
- Uncontrolled diabetes mellitus, including baseline fasting blood glucose > 2×ULN.
- Presence of active infections requiring intravenous antibacterial drugs or inpatient intervention.
- History of other confirmed malignant tumors (excluding those with complete treatment and expected no recurrence within 5 years).
- Known hypersensitivity to any ingredients or excipients of Lutetium-177 Oxotreotide Injection and octreotide acetate microspheres.
- Contraindications to contrast-enhanced CT and MRI contrast agents due to allergic reactions or renal insufficiency.
- Any uncontrolled diseases, mental disorders or surgical conditions that may affect study completion (including poor treatment compliance) or make subjects ineligible for the investigational product.
- Based on the patient's disease characteristics, the investigator judges that alternative treatments such as chemotherapy and targeted therapy are more suitable for the patient than the study treatment, meaning the investigational product is not the optimal clinical treatment option.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Lutetium[177Lu] Oxodotreotide Injection
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Participants will receive 7.4GBq (200mCi) Lutetium[177Lu] Oxodotreotide Injection every 8 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Incidence and severity of adverse events (AE) (Part1)
Time Frame: Until 6 months after the last dose
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Until 6 months after the last dose
|
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Overall Response Rate (ORR) assessed by Independent Review Committee (IRC) (Part 2)
Time Frame: Until disease progression or death, up to 5 years
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Until disease progression or death, up to 5 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Overall Response Rate (ORR) (Part 1)
Time Frame: Until disease progression or death, up to 5 years
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Until disease progression or death, up to 5 years
|
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Progression-free survival (PFS) (Part 1)
Time Frame: Until disease progression or death, up to 5 years
|
Until disease progression or death, up to 5 years
|
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Disease Control Rate (DCR) (Part 1)
Time Frame: Until disease progression or death, up to 5 years
|
Until disease progression or death, up to 5 years
|
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Duration of Overall Response (DoR) (Part 1)
Time Frame: Until disease progression or death, up to 5 years
|
Until disease progression or death, up to 5 years
|
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Time to Progression (TTP) (Part 1)
Time Frame: Until disease progression or death, up to 5 years
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Until disease progression or death, up to 5 years
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PFS rate at 12 months (Part 1)
Time Frame: At 12 months after the first dose
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At 12 months after the first dose
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Overall Survival (OS) (Part 1)
Time Frame: Until death of any cause, up to 5 years
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Until death of any cause, up to 5 years
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Change From Baseline in the EORTC QLQ-C30 Questionnaire (Part 1)
Time Frame: Until disease progression or death, up to 5 years
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Until disease progression or death, up to 5 years
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Change From Baseline in the EORTC Quality of Life Questionnaire (Part 1)
Time Frame: Until disease progression or death, up to 5 years
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Until disease progression or death, up to 5 years
|
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Progression-free survival (PFS) (Part 2)
Time Frame: Until disease progression or death, up to 5 years
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Until disease progression or death, up to 5 years
|
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Disease Control Rate (DCR) (Part 2)
Time Frame: Until disease progression or death, up to 5 years
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Until disease progression or death, up to 5 years
|
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Duration of Overall Response (DoR) (Part 2)
Time Frame: Until disease progression or death, up to 5 years
|
Until disease progression or death, up to 5 years
|
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Overall Survival (OS) (Part 2)
Time Frame: Until death of any cause, up to 5 years
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Until death of any cause, up to 5 years
|
|
Change From Baseline in the EORTC QLQ-C30 Questionnaire (Part 2)
Time Frame: Until disease progression or death, up to 5 years
|
Until disease progression or death, up to 5 years
|
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Incidence and severity of AE (Part2)
Time Frame: Until 6 months after the last dose
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Until 6 months after the last dose
|
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ORR assessed by investigators (part 2)
Time Frame: Until disease progression or death, up to 5 years
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Until disease progression or death, up to 5 years
|
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Change From Baseline in the EORTC Quality of Life GI.NET21 Questionnaire (Part 2)
Time Frame: Until disease progression or death, up to 5 years
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Until disease progression or death, up to 5 years
|
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The proportion of subjects with a reduction of at least 50% from baseline in antihypertensive medication that was sustained for more than 6 months (evaluated only in subjects with hypertension)
Time Frame: Until disease progression or death, up to 5 years
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Until disease progression or death, up to 5 years
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- XT-XTR008-2-02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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