A Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Radiation Dosimetry, Pharmacokinetics, and Preliminary Diagnostic Performance of [⁶⁴Cu]Cu-RAX301 Injection in Patients With Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 52
- 主要终点
- The safety and tolerability of [⁶⁴Cu]Cu-RAX301 Injection - Phase 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria to be eligible for enrollment:
- •Able to provide written informed consent prior to initiation of any study-specific procedures.
- •Male participants aged ≥18 years.
- •Histologically confirmed prostate cancer.
- •ECOG performance status 0 to
- •Life expectancy of at least 6 months.
- •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.
- •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):
- •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.
- •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.
- •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.
- •Creatinine clearance ≥50 mL/min, as calculated using the Cockcroft-Gault formula.
- •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.
- •Participants must meet all of the following criteria to be eligible for enrollment:
- •Able to provide written informed consent prior to initiation of any study-specific procedures.
- •Male participants aged ≥18 years.
- •Histologically confirmed prostate cancer.
- •ECOG performance status of 0-
- •Estimated life expectancy ≥6 months.
- •Creatinine clearance ≥50 mL/min, as calculated using the Cockcroft-Gault formula.
- •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
- •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).
- •Participants have previously undergone definitive therapy.
- •Participants with suspected prostate cancer recurrence based on rising PSA levels following definitive therapy, defined as follows:
- •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
- •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
- •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.
- •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):
- •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.
- •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.
- •Very high-risk prostate cancer, defined as meeting at least two of the following criteria:
- •Clinical stage cT3b-cT4;
- •GG 4 or 5;
- 另有 1 项未显示
排除标准
- •Participants meeting any of the following criteria will be excluded from the study:
- •Known or suspected hypersensitivity to the active component(s) of [⁶⁴Cu]Cu-RAX301 Injection or any of its excipients.
- •Inability to complete [⁶⁴Cu]Cu-RAX301 Injection PET/CT imaging as required by the protocol.
- •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.
- •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.
- •Prior treatment with androgen deprivation therapy (ADT) or any other neoadjuvant therapy.
- •Receipt of high-energy gamma radiation (>300 keV) prior to dosing, within 5 half-lives of the investigational product.
- •QTcF interval ≥470 msec on 12-lead ECG (corrected using Fridericia's formula).
- •Any medical condition that, in the investigator's judgment, may compromise participant safety, protocol compliance, or interpretation of study results.
- •Known or suspected hypersensitivity to the active component(s) of [⁶⁴Cu]Cu-RAX301 Injection or any of its excipients.
- •Inability to complete [⁶⁴Cu]Cu-RAX301 Injection PET/CT imaging as required by the protocol.
- •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.
- •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.
- •Receipt of high-energy gamma radiation (>300 keV) prior to dosing, within 5 half-lives of the investigational product.
- •QTcF interval ≥470 msec on 12-lead ECG (corrected using Fridericia's formula).
- •Any medical condition that, in the investigator's judgment, may compromise participant safety, protocol compliance, or interpretation of study results.
- •Additional Exclusion Criteria Applicable to Cohort 1 (BCR Cohort) Only
- •Receipt of systemic anticancer therapy for prostate cancer within 90 days prior to dosing (including but not limited to androgen deprivation therapy, antiandrogens, gonadotropin-releasing hormone agonists or antagonists, bone-targeted radiopharmaceuticals, or radiotherapy).
- •Exclusion Criteria - Applicable to Phase II Cohort 2 (pre-RP Cohort) Only
- •Prior treatment with androgen deprivation therapy (ADT) or any other neoadjuvant therapy.
研究组 & 干预措施
[⁶⁴Cu]Cu-RAX301 PET/CT
Participants will receive a single intravenous administration of [⁶⁴Cu]Cu-RAX301 Injection followed by protocol-specified PET/CT imaging. In Phase I, pre-RP participants will receive either 5 ± 10% mCi or 8 ± 10% mCi [⁶⁴Cu]Cu-RAX301 Injection, with 6 participants in each administered activity group. The Phase I results will support selection of the administered activity for Phase II. In Phase II, participants in the BCR and pre-RP expansion cohorts will receive the selected administered activity and undergo PET/CT imaging at 4 ± 1 hours and 24 ± 2 hours after administration.
干预措施: [⁶⁴Cu]Cu-RAX301 Injection (Drug)
结局指标
主要结局
The safety and tolerability of [⁶⁴Cu]Cu-RAX301 Injection - Phase 1
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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)
- 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)
- 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)
- PET/CT Uptake and Biodistribution Parameters - Phase II(4 ± 1 hours and 24 ± 2 hours after administration)
- 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)
- Incidence and Severity of Adverse Events and Serious Adverse Events - Phase II(From administration of [⁶⁴Cu]Cu-RAX301 through Day 7 ± 2 days)