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| Name | Class |
|---|---|
| Sinotau Pharmaceutical Group | INDUSTRY |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 24 months after last dose administration |
| PFS |
| Measure | Description | Time Frame |
|---|---|---|
| Whole body and organ uptake of [225Ac]Ac-DOTATATE | To estimate the absorbed doses of target organs and lesions. | 8 weeks after the first dose administration |
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 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.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhi Yang | Contact | 010-88196196 | pekyz@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Cancer Hospital & Institute | Recruiting | Beijing | Beijing Municipality | 100000 | China |
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| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| ID | Term |
|---|---|
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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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.
| 24 months after last dose administration |
| 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. | 24 months after last dose administration |
| 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). | 24 months after last dose administration |
| DCR | DCR is defined as the incidence of complete response, partial response and stable disease assessed by investigator according to RECIST v1.1. | 24 months after last dose administration |
| 12-month PFS Rate | 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. | From date of enrollment until date of progression or date of death from any cause, whichever comes first,assessed up to approximately 24 months |
| D009380 | Neoplasms, Nerve Tissue |