Metastatic Castration-resistant Prostate Cancer
Conditions
Brief summary
This is a pilot study to assess the safety and measure image-based absorbed dose of 177Lu-P17-087/177Lu-P17-088 in patients with metastatic castration-resistant prostate cancer (mCRPC) who will undergo radioliagnd therapy using 177Lu-P17-087/177Lu-P17-088. All patients underwent whole-body 68Ga-PSMA PET/CT for selection and accepted intravenous injection with single dose 1.1 GBq (30 mCi) of 177Lu-P17-087/177Lu-P17-088 within one week, then monitored at 1.5 hours, 4 hours, 24 hours, 48 hours, 72 hours, 120 hours and 168 hours after 177Lu-P17-087/177Lu-P17-088 administration with serial whole body planar and SPECT/CT imaging.Following this initial safety assessment, the study will proceed to a dose-escalation phase designed to further evaluate safety and determine the optimal therapeutic activity. The dose-escalation phase will enroll patients into three sequential cohorts: a 1.11 GBq (30 mCi) dose group, a 2.96 GBq (80 mCi) dose group, and a 4.44 GBq (120 mCi) dose group.
Detailed description
Prostate cancer is the most frequent malignant tumor in men worldwide. Prostate-specific membrane antigen (PSMA), is a surface molecule specifically expressed by prostate tumors which was shown to be a valid target for radiotherapy. 177Lu-PSMA-617, a urea-based compound, provide an effective target for the treatment of metastatic castration-resistant prostate cancer. However, a major problem in the therapeutic use of 177Lu-PSMA-617 has been its short half-life and fast rate of clearance. The investigators designed and synthesized a new radiopharmaceutical based on PSMA-11, P16-093. 68Ga-P16-093 showed higher tumor uptake and clear blood clearance than 68Ga-PSMA-617. Then, the investigators shynthesis a new therapeutic radiopharmaceutical based on P16-093, P17-087; and the investigators added a selected albumin binder into P17-088 to synthesis another new radiopharmaceutical, P17-088. This study is designed to evaluate the safety, dosimetry, and preliminary antitumor activity of 177Lu-P17-087/177Lu-P17-088. The trial will include an initial dose-escalation phase to identify the maximum tolerated dose (MTD) or optimal biological dose, which will be followed by a dose-expansion phase to confirm safety and further characterize pharmacokinetics and efficacy, thereby establishing the Recommended Phase II Dose (RP2D) for future development.
Interventions
DRUG1.1 GBq (30 mCi) of 177Lu-P17-087
All patients were intravenous injected with single dose 1.1 GBq (30 mCi) of 177Lu-P17-087 then monitored at 1.5 hours, 4 hours, 24 hours, 48 hours, 72 hours, 120 hours and 168 hours post-injection.
DRUG1.1 GBq (30 mCi) of 177Lu-P17-088
All patients were intravenous injected with single dose 1.1 GBq (30 mCi) of 177Lu-P17-088 then monitored at 1.5 hours, 4 hours, 24 hours, 48 hours, 72 hours, 120 hours and 168 hours post-injection.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* All the patients had progressive metastatic castration-resistant prostate cancer that did not respond to androgen-suppression therapy and/or systemic chemotherapy; * Distant metastases with high PSMA expression were confirmed on 68Ga-PSMA PET/CT within one week before the injection of 177Lu-P17-087/177Lu-P17-088.
Exclusion criteria
* Patients were excluded if they had \[18F\]FDG positive tumors without corresponding PSMA uptake. Patients were also not eligible if they accepted other radionuclide therapies within 6 months or had clinically significant impaired bone marrow, liver, or kidney function with a hemoglobin level of less than 9.0 g/dL, a white blood cell count of less than 2.5×109/L, a platelet count of less than 100×109/L and a serum creatinine \> 100 μmol/L.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dosimetry of normal organs and tumors | Determined using imaging at 1.5 hours, 4 hours, 24 hours, 48 hours, 72 hours, 120 hours and 168 hours after the first administration of 177Lu-P17-087/088 | The semiquantitative dosimetry will be performed based on SPECT/CT acquisitions after the administration of 177Lu-P17-087/177Lu-P17-088. The dose delivered to normal organs and tumors will be recorded. |
| Hematologic adverse events collection | through study completion, an average of 2 weeks | 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. |
| Hepatic and renal toxic events collection | through study completion, an average of 2 weeks | Liver function, and renal function were performed before and 6 weeks after administration of radiopharmaceutical. Adverse events were categorized using the Common Toxicity Criteria for Adverse Events 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA Response | through study completion, an average of 3 weeks | The serum PSA response was documented semimonthly until 6 weeks after the administration of 177Lu-P17-087/177Lu-P17-088. 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%. |
| PSMA Response | 6 weeks after treatment administration. | Treatment efficacy will be assessed by comparing PSMA-expression on PET/CT at baseline to the scan obtained at the 6-week follow-up. Tumor response will be evaluated according to the RECIP 1.0 criteria. |
Countries
China
Contacts
Primary ContactZhaohui Zhu, MD
Backup ContactGuochang Wang, MD
Outcome results
None listed