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

NCT06732505 | Recruiting Phase 1 DMC

• 1 other identifier: IIT-XT024-1-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Keywords

[225Ac]Ac-DOTATATE; neuroendocrine neoplasm

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of 225Ac-DOTATATE

  Incidence and severity of adverse events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

  32 weeks following first 225Ac-DOTATATE injection

• Recommended phase II dose of 225Ac-DOTATATE

  Rate incidence of dose-limiting toxicities (DLT)

  First 56 days following first 225Ac-DOTATATE injection

Secondary Outcomes (6)

• ORR

  24 months after last dose administration

• PFS

  24 months after last dose administration

• DoR

  24 months after last dose administration

• TTP

  24 months after last dose administration

• DCR

  24 months after last dose administration

Other Outcomes (1)

• Whole body and organ uptake of [225Ac]Ac-DOTATATE

  8 weeks after the first dose administration

Study Arms (1)

[225Ac]Ac-DOTATATE

EXPERIMENTAL

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

Drug: [225Ac]Ac-DOTATATE

Interventions

[225Ac]Ac-DOTATATE 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.

[225Ac]Ac-DOTATATE

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have the ability to understand and sign an approved informed consent form (ICF).
• Patients must be \>= 18 and \<＝80 years of age.
• Histopathologically confirmed G1 or G2 or G3 GEP-NET or GEP-NEC；
• Unresectable locally advanced or metastatic GEP-NET which confirmed by imaging examination.
• 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.
• Presence of at least 1 measurable site of disease (based on RECIST 1.1).
• SSTR-PET positive.
• ECOG score of 0 or 1.
• Life expectancy of at least 12 weeks.
• 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.
• 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.

You may not qualify if:

• Pregnant or lactating females.
• 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.
• Received systemic antitumor therapy such as targeted therapy, immunotherapy, antitumor herbal therapy, chemotherapy within 4 weeks prior to initiation of study treatment.
• Rapid progression with previous PRRT therapy.
• 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.
• Toxicity of prior antitumor therapy has not returned to ≤ grade 1 levels (except for alopecia).
• Received external beam radiation therapy for bone metastases within 2 weeks prior to initiation of study treatment.
• Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrollment in the study.
• Uncontrolled congestive heart failure.
• uncontrolled diabetes mellitus, including baseline fasting glucose \> 2 x ULN.
• Known other malignancies (except for those without recurrence within 5 years after adequate treatment).
• Known hypersensitivity to Lutetium\[177Lu\] Oxodotreotide Injection or \[225Ac\]Ac-DOTATATE Injection and their excipients.
• Known to be unsuitable for enhanced CT or MRI contrast imaging due to allergic reaction or renal insufficiency.
• Any clinically significant active infection.
• Participated in other drug clinical trials within 4 weeks prior to initiation of study treatment and received treatment with the corresponding trial drug.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead
• Sinotau Pharmaceutical Group: collaborator

Study Sites (1)

Peking University Cancer Hospital & Institute

Beijing, Beijing Municipality, 100000, China

RECRUITING

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Central Study Contacts

Zhi Yang

CONTACT

010-88196196; pekyz@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: December 13, 2024
• Study Start: September 29, 2024
• Primary Completion: December 31, 2025
• Study Completion: March 31, 2026
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)