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).
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.
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.
Sequential
[225Ac]Ac-DOTATATE
DrugThe 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.
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
Recommended phase II dose of 225Ac-DOTATATE
Rate incidence of dose-limiting toxicities (DLT)
ORR
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
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
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
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).
Whole body and organ uptake of [225Ac]Ac-DOTATATE
To estimate the absorbed doses of target organs and lesions.
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Peking University Cancer Hospital & Institute
Lead sponsor
Sinotau Pharmaceutical Group
Collaborator
