177Lu-P17-087/177Lu-P17-088 in Patients With Metastatic Castration-resistant Prostate Cancer

Early Phase 1RecruitingNCT05603559

Peking Union Medical College Hospital30 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Interventions

1.1 GBq (30 mCi) of 177Lu-P17-087DRUG

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.

1.1 GBq (30 mCi) of 177Lu-P17-088DRUG

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.

Eligibility

Sex: MALEMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Dosimetry of normal organs and tumors

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.

Time frame: 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

Hematologic adverse events collection

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.

Time frame: through study completion, an average of 2 weeks

Hepatic and renal toxic events collection

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.

Time frame: through study completion, an average of 2 weeks

Secondary Outcomes

PSA Response

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%.

Time frame: through study completion, an average of 3 weeks

PSMA Response

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.

Time frame: 6 weeks after treatment administration.