Clinical trial NCT06732505: A Phase I Study to Assess the Safety and Efficacy of [225Ac]Ac-DOTATATE in Patients with SSTR+ GEP-Nets
Official title: 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-Nets
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neuroendocrine Tumors
Keywords: neuroendocrine tumors
[225Ac]Ac-DOTATATE
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
Collaborators: name: Sinotau Pharmaceutical Group
First posted: 2024-12-13
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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；
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.

Primary outcomes:
measure: Safety and tolerability of 225Ac-DOTATATE
timeFrame: 32 weeks following first 225Ac-DOTATATE injection
measure: Recommended phase II dose of 225Ac-DOTATATE
timeFrame: First 56 days following first 225Ac-DOTATATE injection
Secondary outcomes:
measure: ORR
timeFrame: 24 months after last dose administration
measure: PFS
timeFrame: 24 months after last dose administration
measure: DoR
timeFrame: 24 months after last dose administration
measure: TTP
timeFrame: 24 months after last dose administration
measure: DCR
timeFrame: 24 months after last dose administration
measure: 12-month PFS Rate
timeFrame: From date of enrollment until date of progression or date of death from any cause, whichever comes first，assessed up to approximately 24 months
Other outcomes:
measure: Whole body and organ uptake of [225Ac]Ac-DOTATATE
timeFrame: 8 weeks after the first dose administration
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital & Institute
state: Beijing
Study officials:
References: