A Phase I Study to Assess the Safety and Efficacy of [225Ac]Ac-DOTATATE in Patients With SSTR+ GEP-Nens

A Phase I Study to Assess the Safety and Efficacy of [225Ac]Ac-DOTATATE in Patients With Inoperable, Locally Advanced or Metastatic, Progressive, Well-Differentiated,SSTR+ GEP-Nens

This is a phase I study to assess the safety and efficacy of [225Ac]Ac-DOTATATE in patients with inoperable, locally advanced or metastatic, progressive, Well-Differentiatedwell differentiated, somatostatin receptor positive gastroenteropancreatic neuroendocrine neoplasms with either no prior history of peptide receptor radionuclide therapy (PRRT naive) or prior history of peptide receptor radionuclide therapy (Previous PRRT).

Inclusion Criteria:

1. Patients must have the ability to understand and sign an approved informed consent form (ICF).

2. Patients must be >= 18 and <＝80 years of age.

3. Histopathologically confirmed G1 or G2 or G3 GEP-NET or GEP-NEC；

4. Unresectable locally advanced or metastatic GEP-NET which confirmed by imaging examination.

5. G1 or G2 NET patients: previously received fixed-dose Octreotide LAR (20-30 mg/3-4 weeks) for at least 12 weeks of continuous treatment with disease progression;G3 NET orNEC patients: previously received at least 1 line therapy with disease progression.

6. Presence of at least 1 measurable site of disease (based on RECIST 1.1).

7. SSTR-PET positive.

8. ECOG score of 0 or 1.

9. Life expectancy of at least 12 weeks.

10. Sufficient bone marrow capacity and organ function:

    Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 ml/min (Cockcroft Gault formula).

    Hemoglobin≥90g/L, neutrophil count ≥1.5×10^9/L, platelets≥100×10^9/L. Serum total bilirubin ≤1.5×ULN. Serum albumin ≥30g/L. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5×ULN，or ALT/AST≤5×ULN with liver metastases.

    Partially activated prothrombin time (APTT) ≤1.5 x ULN.

11. Subjects of childbearing potential voluntarily use an effective method of contraception, such as condoms, oral or injectable contraceptives, IUDs, etc., during treatment and within 6 months of the last use of the trial drug.

Exclusion Criteria:

1. Pregnant or lactating females.
2. Received the following treatments within 4 weeks prior to initiation of study treatment, including but not limited to surgery (except biopsy), radical radiotherapy, hepatic artery interventional embolization, cryoablation of liver metastases, or radiofrequency ablation.
3. Received systemic antitumor therapy such as targeted therapy, immunotherapy, antitumor herbal therapy, chemotherapy within 4 weeks prior to initiation of study treatment.
4. Rapid progression with previous PRRT therapy.
5. Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of initiation of study treatment, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 6 weeks before the administration of initiation of study treatment.
6. Toxicity of prior antitumor therapy has not returned to ≤ grade 1 levels (except for alopecia).
7. Received external beam radiation therapy for bone metastases within 2 weeks prior to initiation of study treatment.
8. Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrollment in the study.
9. Uncontrolled congestive heart failure.
10. uncontrolled diabetes mellitus, including baseline fasting glucose > 2 x ULN.
11. Known other malignancies (except for those without recurrence within 5 years after adequate treatment).
12. Known hypersensitivity to Lutetium[177Lu] Oxodotreotide Injection or [225Ac]Ac-DOTATATE Injection and their excipients.
13. Known to be unsuitable for enhanced CT or MRI contrast imaging due to allergic reaction or renal insufficiency.
14. Any clinically significant active infection.
15. Participated in other drug clinical trials within 4 weeks prior to initiation of study treatment and received treatment with the corresponding trial drug.
16. 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.
17. 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.
18. Unsuitable for the study for any reason, in the opinion of the investigator.