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

NCT ID: NCT06732505

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-29
• Study Completion Date: 2026-03-31

Brief Summary

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).

Conditions

Neuroendocrine Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

[225Ac]Ac-DOTATATE

Investigational radiotherapeutic drug targeting somatostatin receptor-positive neuroendocrine neoplasms in PRRT naive patients (Cohort 1) and previous PRRT patients (Cohort 2)

Group Type: EXPERIMENTAL

[225Ac]Ac-DOTATATE

Intervention Type: DRUG

The dose escalation phase will be divided into two cohorts: patients who had previously received 177Lu-PRRT will be enrolled in cohort 1, and patients who had not received 177Lu-PRRT will be enrolled in cohort 2. Dose escalation was performed independently in the two cohorts. DL1 will be administered as a dose of 90kBq/kg per cycle, and DL2 will be administered as a single dose of 120kBq/kg per cycle.Every patient will receive one [225Ac]Ac-DOTATATE infusion every 8 weeks for up to 4 cycles.

The dose expansion phase will be divided into 3 cohorts based on Ki-67 index.

Interventions

[225Ac]Ac-DOTATATE

The dose escalation phase will be divided into two cohorts: patients who had previously received 177Lu-PRRT will be enrolled in cohort 1, and patients who had not received 177Lu-PRRT will be enrolled in cohort 2. Dose escalation was performed independently in the two cohorts. DL1 will be administered as a dose of 90kBq/kg per cycle, and DL2 will be administered as a single dose of 120kBq/kg per cycle.Every patient will receive one [225Ac]Ac-DOTATATE infusion every 8 weeks for up to 4 cycles.

The dose expansion phase will be divided into 3 cohorts based on Ki-67 index.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sinotau Pharmaceutical Group

INDUSTRY

Sponsor Role: collaborator

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Peking University Cancer Hospital & Institute

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhi Yang

Role: CONTACT

pekyz@163.com

010-88196196

Facility Contacts

Yang

Role: primary

pekyz@163.com

010-88196196

Other Identifiers

IIT-XT024-1-01

Identifier Type: -

Identifier Source: org_study_id