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

Phase 1

Recruiting

• Conditions: Neuroendocrine Tumors
• Interventions: Drug: [225Ac]Ac-DOTATATE

• Registration Number: NCT06732505
• Lead Sponsor: Peking University Cancer Hospital & Institute

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 (G1/G2/G3 ), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors with either no prior history of peptide receptor radionuclide therapy (PRRT naive) or prior history of peptide receptor radionuclide therapy (Previous PRRT).

Detailed Description

Not available

Study Timeline

• Study Start: 2024-09-29
• Study First Submitted: 2024-12-10
• Study First Submitted QC: 2024-12-10
• Study First Posted: 2024-12-13
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-13
• Last Update Posted: 2025-02-14
• Primary Completion: 2025-12-31
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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；

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

5. G1 or G2 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 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
[225Ac]Ac-DOTATATE	[225Ac]Ac-DOTATATE	Investigational radiotherapeutic drug targeting somatostatin receptor-positive neuroendocrine tumors in PRRT naive patients (Cohort 1) and previous PRRT patients (Cohort 2)

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of 225Ac-DOTATATE	32 weeks following first 225Ac-DOTATATE injection	Incidence and severity of adverse events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Recommended phase II dose of 225Ac-DOTATATE	First 56 days following first 225Ac-DOTATATE injection	Rate incidence of dose-limiting toxicities (DLT)

Secondary Outcome Measures

Name	Time	Method
ORR	24 months after last dose administration	ORR was calculated as the proportion of patients with tumour size reduction (sum of partial responses (PR) and complete responses (CR)) and assessed by investigator according to RECIST 1.1.
PFS	24 months after last dose administration	PFS will be defined as the number of days from the first dose of \[225Ac\]-DOTATATE to documented tumor progression per RECIST 1.1 criteria or death due to any cause.
DoR	24 months after last dose administration	DoR was defined as the time from initially meeting the criteria for response (CR or PR) until the time of progression and assessed by investigator according to RECIST 1.1.
TTP	24 months after last dose administration	TTP was defined as the time from randomization to progression assessed by investigator. It included patients who dropped out due to toxicity, but omitted patients who died without measured progression (censored to last follow-up date or death date).
DCR	24 months after last dose administration	DCR is defined as the incidence of complete response, partial response and stable disease assessed by investigator according to RECIST v1.1.
12-month PFS Rate	From date of enrollment until date of progression or date of death from any cause, whichever comes first，assessed up to approximately 24 months	12-month Progression-Free Survival rate was defined as the proportion of patients whose time from enrollment to disease progression according to RECIST v1.1 or death exceeds 12 months.

Trial Locations

Locations (2)

Peking University Cancer Hospital & Institute; 🇨🇳 Beijing, Beijing, China

Peking University Cancer Hospital & Institute; 🇨🇳 Beijing, Beijing, China