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

Peking University Cancer Hospital & Institute1 site in 1 country36 target enrollmentSeptember 29, 2024

Interventions[225Ac]Ac-DOTATATE

Drugs[225Ac]Ac-DOTATATE

Overview

Phase: Phase 1
Intervention: [225Ac]Ac-DOTATATE
Conditions: Not specified
Sponsor: Peking University Cancer Hospital & Institute
Enrollment: 36
Locations: 1
Primary Endpoint: Safety and tolerability of 225Ac-DOTATATE
Status: Recruiting
Last Updated: 10 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

September 29, 2024

End Date

March 31, 2026

Last Updated

10 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Peking University Cancer Hospital & Institute

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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
•Life expectancy of at least 12 weeks.
•Sufficient bone marrow capacity and organ function:

Exclusion Criteria

•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.

Arms & Interventions

[225Ac]Ac-DOTATATE

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

Intervention: [225Ac]Ac-DOTATATE

Outcomes

Primary Outcomes

Safety and tolerability of 225Ac-DOTATATE

Time Frame: 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

Time Frame: First 56 days following first 225Ac-DOTATATE injection

Rate incidence of dose-limiting toxicities (DLT)

Secondary Outcomes

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)
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)