Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
PSMA, 177Lu, mCRPC
Brief summary
This study employed an open-label, non-randomized design, representing the first human trial of its kind. It utilized a standard 3+3 dose-escalation approach, focusing on patients with metastatic castration-resistant prostate cancer, initiating treatment at a dose of 1.85 GBq over a 6-week period. Subsequent cohorts underwent sequential 50% dose escalations until the observation of dose-limiting toxicity (DLT).
Detailed description
\[177Lu\]Lu-LNC1011 is a novel long-circulating PSMA therapeutic probe. This study represents the first human investigation, aiming to explore its maximum tolerated dose (MTD), safety, dosimetry, and initial treatment efficacy in patients with metastatic castration-resistant prostate cancer (mCRPC).This study employed an open-label, non-randomized design, representing the first human trial of its kind. It utilized a standard 3+3 dose-escalation approach, focusing on patients with metastatic castration-resistant prostate cancer, initiating treatment at a dose of 1.85 GBq over a 6-week period. Subsequent cohorts received a dose escalation of 0.925 GBq from the previous cohort.
Interventions
DRUG177Lu-LNC1011
\[177Lu\]Lu-LNC1011 is a novel long-circulating PSMA therapeutic probe.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* progressive metastatic castration-resistant prostate cancer * tumors with high PSMA expression confirmed on 68Ga-PSMA PET/CT PSMA expression confirmed on 68Ga-PSMA PET/CT
Exclusion criteria
* a serum creatinine level of more than 150 μmol per liter * a hemoglobin level of less than 10.0 g/dl * a white-cell count of less than 4.0× 109/L * a platelet count of less than 100 × 109/L * a total bilirubin level of more than 3 times the upper limit of the normal range * a serum albumin level of more than 3.0 g per deciliter * cardiac insufficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dosimetry of normal organs and tumors | through study completion, an average of 4 weeks | The semiquantitative dosimetry will be performed based on SPECT/CT acquisitions after the first administration of 177Lu-LNC1011. The dose delivered to normal organs and tumors will be recorded. |
| Hematologic adverse events collection | through study completion, an average of 6 months | Hematologic status were performed before and every 2 weeks after administration of radiopharmaceutical. Adverse events were categorized using the Common Toxicity Criteria for Adverse Events 5.0:Total white cell count less than 2.5 × 10\^9/L,Platelet count less than 75 × 10\^9/L |
| Liver and renal toxic events collection | through study completion, an average of 6 months | Liver and renal function were performed before and 4 weeks after administration of radiopharmaceutical. Adverse events were categorized using the Common Toxicity Criteria for Adverse Events 5.0:Progressive deterioration of organ function (GFR \<30 mL/min or creatinine \> 2-fold upper limit of normal (ULN); liver enzymes \> 5-fold ULN). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA Response | through study completion, an average of 6 months | The serum PSA response was documented semimonthly until 6 weeks after the administration of 177Lu-LNC1011. PSA response was classified as the following: partial response (PR) if PSA decrease ≥50%, progressive disease (PD) if PSA increase ≥ 25% and stable disease (SD) if PSA increase \<25% or PSA decrease \<50%. |
| Pharmacokinetics and dosimetry | Whole-body (WB) scans were performed at 2, 4, 24, 48, 72, 120, and 168 hours following intravenous administration of [177Lu]Lu-LNC1011 | Absorbed doses were measured in the brain, salivary glands, thyroid, cardiac content, lungs, liver, kidneys, spleen, pancreas, L2-L4 lumbar vertebrae, gastric content, and bladder content. |
Countries
China
Contacts
Primary ContactZhaohui Zhu, MD
Backup ContactJiarou Wang, MD
Outcome results
None listed