Prostate Cancer
Conditions
Keywords
pre-RP, BCR, PSMA PET, [⁶⁴Cu]Cu-RAX301, Prostate Cancer, RAX301, Biochemical Recurrence, Pre-Radical Prostatectomy, Copper-64, Radiopharmaceutical Imaging, PET/CT
Brief summary
This is a prospective, open-label, multicenter, Phase I/II exploratory diagnostic imaging study to evaluate the safety, tolerability, radiation dosimetry, pharmacokinetics, biodistribution, imaging characteristics, and preliminary diagnostic performance of \[⁶⁴Cu\]Cu-RAX301 Injection in patients with prostate cancer. Phase I will evaluate two administered activity levels of \[⁶⁴Cu\]Cu-RAX301 Injection in participants scheduled to undergo radical prostatectomy and pelvic lymph node dissection (pre-RP population) and will support selection of the administered activity for Phase II. Phase II will evaluate the selected administered activity in two independent expansion cohorts: participants with suspected recurrence or biochemical recurrence of prostate cancer and participants scheduled to undergo radical prostatectomy and pelvic lymph node dissection.
Detailed description
COPRA424 is a prospective, open-label, multicenter, Phase I/II exploratory diagnostic imaging study of \[⁶⁴Cu\]Cu-RAX301 Injection, a prostate-specific membrane antigen (PSMA)-targeted PET radiodiagnostic agent, in patients with prostate cancer. Approximately 52 participants are planned for enrollment: 12 participants in Phase I and approximately 40 participants in Phase II. In Phase I, 12 participants with prostate cancer who are scheduled to undergo radical prostatectomy and pelvic lymph node dissection will be assigned by administered activity to receive a single intravenous administration of either 5 ± 10% mCi or 8 ± 10% mCi \[⁶⁴Cu\]Cu-RAX301 Injection, with 6 participants in each activity group. Participants will undergo serial PET/CT imaging for biodistribution and radiation dosimetry assessments and blood and urine sampling for pharmacokinetic, radioactivity excretion, and metabolite analyses. Imaging characteristics will also be evaluated at 4 ± 1 hours and 24 ± 2 hours after administration. Safety, tolerability, biodistribution, radiation dosimetry, pharmacokinetics, imaging characteristics, and preliminary diagnostic performance will be evaluated to support selection of the administered activity for Phase II. Phase II will use the administered activity selected based on Phase I and will include two independent expansion cohorts. Cohort 1 will enroll approximately 20 participants with suspected recurrence or biochemical recurrence of prostate cancer. Cohort 2 will enroll approximately 20 participants scheduled to undergo radical prostatectomy and pelvic lymph node dissection. Participants will receive a single intravenous administration of \[⁶⁴Cu\]Cu-RAX301 Injection and undergo PET/CT imaging at 4 ± 1 hours and 24 ± 2 hours after administration. Phase II will primarily evaluate the preliminary diagnostic performance, biodistribution characteristics, and safety of \[⁶⁴Cu\]Cu-RAX301 PET/CT in the two target populations. For the pre-RP population, postsurgical histopathology from radical prostatectomy and/or pelvic lymph node dissection will serve as an important component of the standard of truth for evaluation of diagnostic performance. For the biochemical recurrence population, diagnostic performance will be evaluated using a prespecified composite reference standard. Study imaging findings are exploratory and should not serve as the sole basis for major clinical management decisions unless confirmed by non-investigational methods.
Interventions
DRUG[⁶⁴Cu]Cu-RAX301 Injection
\[⁶⁴Cu\]Cu-RAX301 Injection is a PSMA-targeted PET radiodiagnostic agent administered as a single intravenous injection. In Phase I, participants will receive an administered activity of either 5 ± 10% mCi or 8 ± 10% mCi. Serial PET/CT imaging will be performed at approximately 1, 4, 8, 24, and 48 hours after administration for biodistribution and radiation dosimetry assessments, with imaging characteristics evaluated at 4 ± 1 hours and 24 ± 2 hours. In Phase II, participants will receive the administered activity selected based on Phase I and undergo PET/CT imaging at 4 ± 1 hours and 24 ± 2 hours after administration.
Sponsors
RadAlliance Therapeutics, Inc
Shanghai Junkanglitai Biosciences Co. Ltd.
Shanghai Zhongshan Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
This is a single-arm, Phase I/II exploratory diagnostic imaging study. In Phase I, participants scheduled for radical prostatectomy and pelvic lymph node dissection will receive one of two administered activity levels of \[⁶⁴Cu\]Cu-RAX301 Injection (5 ± 10% mCi or 8 ± 10% mCi) to evaluate safety, dosimetry, pharmacokinetics, imaging characteristics, and preliminary diagnostic performance and to support selection of an administered activity for Phase II. Phase II will evaluate the selected administered activity in two independent expansion cohorts: participants with suspected or biochemical recurrence of prostate cancer and participants scheduled for radical prostatectomy and pelvic lymph node dissection.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase I Participants must meet all of the following criteria to be eligible for enrollment: 1. Able to provide written informed consent prior to initiation of any study-specific procedures. 2. Male participants aged ≥18 years. 3. Histologically confirmed prostate cancer. 4. ECOG performance status 0 to 2. 5. Life expectancy of at least 6 months. 6. Clinically assessed as scheduled to undergo radical prostatectomy and pelvic lymph node dissection (including patients with localized disease, regional lymph node metastases, or oligometastatic prostate cancer), with no contraindications to surgery. 7. Participants must meet one of the following risk categories: unfavorable intermediate-risk, high-risk, or very high-risk prostate cancer, as defined according to the NCCN Guidelines (Version 2026, Version 5; PROS-2): 1. Unfavorable intermediate-risk prostate cancer, defined as meeting any of the following criteria: * ISUP Grade Group (GG) 3; or * GG 2 with ≥50% of biopsy cores positive for prostate cancer; and/or * Presence of ≥2 intermediate-risk factors, including clinical stage cT2b or cT2c and PSA 10-20 ng/mL. 2. High-risk prostate cancer, defined as meeting at least one high-risk feature but not meeting criteria for very high-risk disease, including: * Clinical stage cT3a; or * GG 4 or 5; or * PSA \>20 ng/mL. 3. Very high-risk prostate cancer, defined as meeting at least two of the following criteria: * Clinical stage cT3b-cT4; * GG 4 or 5; * PSA \>40 ng/mL. 8. Creatinine clearance ≥50 mL/min, as calculated using the Cockcroft-Gault formula. 9. Male participants must agree to use highly effective contraception for 4 weeks after administration of the investigational product and must refrain from donating sperm during this period. Phase II Participants must meet all of the following criteria to be eligible for enrollment: 1. Able to provide written informed consent prior to initiation of any study-specific procedures. 2. Male participants aged ≥18 years. 3. Histologically confirmed prostate cancer. 4. ECOG performance status of 0-2. 5. Estimated life expectancy ≥6 months. 6. Creatinine clearance ≥50 mL/min, as calculated using the Cockcroft-Gault formula. 7. Male participants must agree to use highly effective contraception for 4 weeks after administration of the investigational product and must refrain from donating sperm during this period. Additional Inclusion Criteria Applicable to Cohort 1 (BCR Cohort) Only 8. Any clinically significant adverse events that occurred during prior therapies (e.g., chemotherapy, radiotherapy, immunotherapy) have resolved to CTCAE Grade ≤2 (with the exception of alopecia). 9. Participants have previously undergone definitive therapy. 10. Participants with suspected prostate cancer recurrence based on rising PSA levels following definitive therapy, defined as follows: 1. Post-radical prostatectomy: detectable or persistently rising PSA levels, with PSA ≥0.2 ng/mL, confirmed by a second measurement showing PSA ≥0.2 ng/mL (per American Urological Association \[AUA\] recommendations); or 2. Post-radiotherapy, cryotherapy, or brachytherapy: PSA increase of ≥2 ng/mL above the nadir, in accordance with the American Society for Radiation Oncology (ASTRO)-Phoenix consensus definition. Additional Inclusion Criteria Applicable to Cohort 2 (pre-RP Cohort) Only 11. Clinically assessed as scheduled to undergo radical prostatectomy and pelvic lymph node dissection (including patients with localized disease, regional lymph node metastases, or oligometastatic prostate cancer), with no contraindications to surgery. 12. Participants must meet one of the following risk categories: unfavorable intermediate-risk, high-risk, or very high-risk prostate cancer, as defined according to the NCCN Guidelines (Version 2026, Version 5; PROS-2): 1. Unfavorable intermediate-risk prostate cancer, defined as meeting any of the following criteria: * ISUP Grade Group (GG) 3; or * GG 2 with ≥50% of biopsy cores positive for prostate cancer; and/or * Presence of ≥2 intermediate-risk factors, including clinical stage cT2b or cT2c and PSA 10-20 ng/mL. 2. High-risk prostate cancer, defined as meeting at least one high-risk feature but not meeting criteria for very high-risk disease, including: * Clinical stage cT3a; or * GG 4 or 5; or * PSA \>20 ng/mL. 3. Very high-risk prostate cancer, defined as meeting at least two of the following criteria: * Clinical stage cT3b-cT4; * GG 4 or 5; * PSA \>40 ng/mL.
Exclusion criteria
Phase I Participants meeting any of the following criteria will be excluded from the study: 1. Known or suspected hypersensitivity to the active component(s) of \[⁶⁴Cu\]Cu-RAX301 Injection or any of its excipients. 2. Inability to complete \[⁶⁴Cu\]Cu-RAX301 Injection PET/CT imaging as required by the protocol. 3. Participation in another interventional clinical trial prior to signing the informed consent form, within 5 half-lives of the investigational product, or current participation in another interventional clinical trial; or prior participation in a radiopharmaceutical clinical trial with a washout period of less than 3 months prior to signing informed consent. 4. Receipt of any intravenous iodinated contrast agent within 24 hours prior to administration of the investigational product, or receipt of any high-density oral contrast agent (e.g., barium sulfate) within 5 days prior to dosing. Oral water-soluble contrast agents (e.g., compound diatrizoate meglumine oral solution) are permitted. 5. Prior treatment with androgen deprivation therapy (ADT) or any other neoadjuvant therapy. 6. Receipt of high-energy gamma radiation (\>300 keV) prior to dosing, within 5 half-lives of the investigational product. 7. QTcF interval ≥470 msec on 12-lead ECG (corrected using Fridericia's formula). 8. Any medical condition that, in the investigator's judgment, may compromise participant safety, protocol compliance, or interpretation of study results. Phase II 1. Known or suspected hypersensitivity to the active component(s) of \[⁶⁴Cu\]Cu-RAX301 Injection or any of its excipients. 2. Inability to complete \[⁶⁴Cu\]Cu-RAX301 Injection PET/CT imaging as required by the protocol. 3. Participation in another interventional clinical trial prior to signing informed consent, within 5 half-lives of the investigational product, or current participation in another interventional clinical trial; or prior participation in a radiopharmaceutical clinical trial with a washout period of less than 3 months prior to signing informed consent. 4. Receipt of any intravenous iodinated contrast agent within 24 hours prior to administration of the investigational product, or receipt of any high-density oral contrast agent (e.g., barium sulfate) within 5 days prior to dosing. Oral water-soluble contrast agents (e.g., compound diatrizoate meglumine oral solution) are permitted. 5. Receipt of high-energy gamma radiation (\>300 keV) prior to dosing, within 5 half-lives of the investigational product. 6. QTcF interval ≥470 msec on 12-lead ECG (corrected using Fridericia's formula). 7. Any medical condition that, in the investigator's judgment, may compromise participant safety, protocol compliance, or interpretation of study results. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The safety and tolerability of [⁶⁴Cu]Cu-RAX301 Injection - Phase 1 | From administration of [⁶⁴Cu]Cu-RAX301 through Day 7 ± 2 days | Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) following administration of \[⁶⁴Cu\]Cu-RAX301 Injection, together with clinically relevant changes from baseline in physical examinations, vital signs, clinical laboratory assessments, and 12-lead electrocardiograms. |
| Participant-Level Correct Detection Rate of [⁶⁴Cu]Cu-RAX301 PET/CT - Phase II BCR Cohort | PET/CT at 4 ± 1 hours and 24 ± 2 hours after administration; standard-of-truth assessment generally through Day 60, with follow-up up to approximately 180 days when PSA response following local radiotherapy is used for confirmation | Participant-level correct detection rate (CDR) of \[⁶⁴Cu\]Cu-RAX301 PET/CT at 4 ± 1 hours and 24 ± 2 hours after administration, based on the prespecified composite standard of truth. CDR is defined as the proportion of scanned participants with at least one true-positive region among participants with at least one evaluable reference-standard assessment. |
| Region-Level Positive Predictive Value of [⁶⁴Cu]Cu-RAX301 PET/CT - Phase II BCR Cohort | PET/CT at 4 ± 1 hours and 24 ± 2 hours after administration; standard-of-truth assessment generally through Day 60, with follow-up up to approximately 180 days when applicable | Region-level positive predictive value (PPV) of \[⁶⁴Cu\]Cu-RAX301 PET/CT at 4 ± 1 hours and 24 ± 2 hours after administration. PPV will be determined among PET-positive regions with an evaluable standard-of-truth status. |
| Participant-Level Sensitivity of [⁶⁴Cu]Cu-RAX301 PET/CT - Phase II pre-RP Cohort | PET/CT at 4 ± 1 hours and 24 ± 2 hours after administration; postsurgical histopathology collected within 28 days after administration | Participant-level sensitivity of \[⁶⁴Cu\]Cu-RAX301 PET/CT at 4 ± 1 hours and 24 ± 2 hours after administration, using postsurgical histopathology from radical prostatectomy and/or pelvic lymph node dissection as the reference standard. |
| Participant-Level Specificity of [⁶⁴Cu]Cu-RAX301 PET/CT - Phase II pre-RP Cohort | PET/CT at 4 ± 1 hours and 24 ± 2 hours after administration; postsurgical histopathology collected within 28 days after administration | Participant-level specificity of \[⁶⁴Cu\]Cu-RAX301 PET/CT at 4 ± 1 hours and 24 ± 2 hours after administration, using postsurgical histopathology from radical prostatectomy and/or pelvic lymph node dissection as the reference standard. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The biodistribution and radiation dosimetry characteristics of [⁶⁴Cu]Cu-RAX301 Injection at 5 ± 10% mCi, and the pharmacokinetic (PK) characteristics of [⁶⁴Cu]Cu-RAX301 Injection at two administered activity levels, 5 ± 10% mCi and 8 ± 10% mCi. | Pre-dose through approximately 48 hours after administration | Measurement of quantitative biodistribution and radiation dosimetry parameters at 5 ± 10% mCi, including uptake parameters in regions of interest (e.g., SUVmax and SUVmean), %ID, residence time, organ absorbed dose, and effective dose. Measurement of pharmacokinetic parameters in blood and plasma, including Cmax, Tmax, t½, AUC₀-t, AUC₀-∞, and CL, as well as whole blood-to-plasma ratios, circulating metabolite profiles, and urinary excretion and metabolite profiles. |
| The imaging characteristics of [⁶⁴Cu]Cu-RAX301 Injection at two PET/CT imaging time points, 4 ± 1 h and 24 ± 2 h after administration - Phase 1. | 4 ± 1 hours and 24 ± 2 hours after administration | Measurement of PET/CT imaging characteristics at 4 ± 1 h and 24 ± 2 h after administration, including lesion uptake parameters (SUVmax and SUVmean), target-to-background ratio (TBR), and image quality assessment, including Likert image quality score and the quantitative image quality parameter of signal-to-noise ratio. Measurement of inter-reader and intra-reader agreement. |
| Preliminary Diagnostic Performance of [⁶⁴Cu]Cu-RAX301 PET/CT - Phase I | PET/CT at 4 ± 1 hours and 24 ± 2 hours after administration; postsurgical histopathology collected within 28 days after administration | Exploratory participant-level and region-level diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). For the pre-RP population, postsurgical histopathology from radical prostatectomy and pelvic lymph node dissection will serve as the reference standard. |
| PET/CT Uptake and Biodistribution Parameters - Phase II | 4 ± 1 hours and 24 ± 2 hours after administration | SUVmax, SUVmean, and target-to-background ratio in relevant organs, tissues, and lesions following administration of \[⁶⁴Cu\]Cu-RAX301. |
| Inter-Reader and Intra-Reader Agreement for [⁶⁴Cu]Cu-RAX301 PET/CT | Based on PET/CT images acquired at 4 ± 1 hours and 24 ± 2 hours after administration | Agreement in interpretation of \[⁶⁴Cu\]Cu-RAX301 PET/CT images between and within central independent readers, assessed using kappa statistics, as applicable. |
| Incidence and Severity of Adverse Events and Serious Adverse Events - Phase II | From administration of [⁶⁴Cu]Cu-RAX301 through Day 7 ± 2 days | Incidence and severity of AEs and SAEs and clinically relevant changes from baseline in physical examination findings, vital signs, clinical laboratory assessments, and 12-lead ECGs. |
Contacts
CONTACTGuangzhou Han, PhD, MD
CONTACTMin Hong, PhD
PRINCIPAL_INVESTIGATORHongcheng Shi, MD PhD
Fudan University
Outcome results
None listed