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| Name | Class |
|---|---|
| Mianyang Central Hospital | OTHER |
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This is a prospective, open-label, single-center, dose-escalation study using a standard 3+3 design to assess the safety, tolerability, biodistribution/dosimetry and preliminary efficacy of the albumin-binding PSMA radioligand 161Tb-LNC1011 in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients will receive intravenous 161Tb-LNC1011 starting at 50 mCi with planned dose-level escalations to 80, 130 and 200 mCi (±10%). Early dose levels (50 mCi) receive 1 cycle; later levels receive up to 4 cycles every 6 weeks based on safety and disease status. Primary endpoints include dose-limiting toxicities (DLTs), adverse events (AEs) graded by CTCAE v5.0, and determination of maximum tolerated dose (MTD). Secondary endpoints include organ/tumor absorbed doses, PSA responses (PSA50/PSA90), disease control, time to PSA progression and radiographic progression-free survival per PCWG3.
Rationale: 161Tb emits β-particles plus abundant low-energy conversion/Auger electrons (very short range, high LET), potentially improving tumoricidal effect-especially for micrometastases-vs 177Lu. LNC1011 is a PSMA ligand with albumin-binding moiety designed to prolong circulation and enhance tumor uptake/retention. Preclinical and early clinical data support feasibility and safety.
Design: 3+3 dose-escalation. Dose levels (activity to be administered IV): 50 mCi (45-55), 80 mCi (72-88), 130 mCi (117-143), 200 mCi (180-220). DLT window: 6 weeks post-dose. If ≥2/6 DLTs, de-escalate; the prior dose is MTD.
Dosing/Cycles: Early dose level (50 mCi) one cycle; later levels up to 4 cycles q6 weeks. Retreatment contingent on hematologic recovery to CTCAE Grade ≤1 or baseline.
Imaging & Dosimetry: Post-dose SPECT/CT at ~30 min, 2 h, 8 h, 24 h, Day 2, Day 7 for time-activity curves and dosimetry. Disease assessments with 68Ga-PSMA-11 PET/CT and labs (PSA, hematology, chemistry) per schedule.
Safety Monitoring: Continuous AE/SAE recording from consent through 28 days post-last dose (or longer if related), DMC oversight (see below).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose-Escalation Cohort (3+3): 161Tb-LNC1011 | Experimental | Single-group, open-label, sequential dose escalation of 161Tb-LNC1011 (IV). Planned dose levels: 50, 80, 130, 200 mCi (±10%). At 50 mCi: 1 cycle; higher levels: up to 4 cycles every 6 weeks, contingent on safety and disease status. DLT window: 6 weeks post-dose; MTD per standard 3+3 rules (≥2/6 DLTs defines exceeding dose). Retreatment requires hematologic recovery to CTCAE ≤ Grade 1 or baseline. Post-dose SPECT/CT at ~30 min, 2 h, 8 h, 24 h, Day 2, Day 7 for dosimetry; disease assessments with 68Ga-PSMA-11 PET/CT and labs per schedule. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 161Tb-LNC1011 | Drug | Intravenous administration; planned dose levels: 50, 80, 130, 200 mCi (±10%); cycle interval q6 weeks; up to 1 cycle at 50 mCi and up to 4 cycles at later dose levels as permitted by safety and disease status. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) | Proportion of participants with DLTs per CTCAE v5.0 during the DLT window. | First 6 weeks after each initial dose at a given dose level |
| Maximum Tolerated Dose (MTD) | Highest dose level at which ≤1/6 participants experience a DLT. | At completion of dose escalation (approximately 12-18 months after study start) |
| Treatment-Emergent Adverse Events (TEAEs) | Number and grade of AEs/SAEs per CTCAE v5.0. | From first dose through 28 days after last dose (extended if related) |
| Measure | Description | Time Frame |
|---|---|---|
| Organ and Tumor Absorbed Doses (Dosimetry) | Absorbed doses to kidneys, salivary glands, tumor lesions, etc., derived from serial SPECT/CT. | Within first cycle (Day 0 to Day 7 imaging) |
| PSA50 and PSA90 Response Rates |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhaohui Zhu, MD | Contact | 86-13611093752 | 13611093752@163.com | |
| Zhengguo Chen, MD | Contact | 86-13908119175 |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking Union Medical College Hospital | Beijing | Beijing Municipality | 100730 | China |
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Intravenous administration; planned dose levels: 50, 80, 130, 200 mCi (±10%); cycle interval q6 weeks; up to 1 cycle at 50 mCi and up to 4 cycles at later dose levels as permitted by safety and disease status.
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Proportion achieving ≥50% and ≥90% PSA decline from baseline, confirmed per PCWG3.
| Every 6 weeks during treatment and at end of treatment (up to approximately 24 weeks) |
| Mianyang Central Hospital | Mianyang | Sichuan | China |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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