Prostate Cancer
Conditions
Keywords
Radiopharmaceutical Therapy, prostate cancer, Prostate Specific Membrane Antigen
Brief summary
The purpose of this study is to evaluate safety and tolerability, pharmacokinetics （PK）, efficacy of TRC003 injection in patients with progressive PSMA-positive mCRPC who have been treated with androgen receptor pathway inhibitor (ARPI) or taxane-based chemotherapy. We plan to recruit 90 participants who will be randomly assigned to 1 of 3 dose cohorts (30 cases per dose cohort) with up to 6 cycles of treatment in this study.
Detailed description
This is a prospective, randomized, open-label, phase 1/2 study on adult patients with PSMA-positive metastatic castration-resistant prostate cancer. Approximately 90 eligible participants will be enrolled and randomized 1:1:1 to three dose cohorts. The first six participants in each cohort will be assessed for dose-limiting toxicity (DLT) during the first treatment cycle. Each eligible participant will receive one of the predefined doses of TRC003 (7.40, 9.25, 11.10 MBq) by intravenous infusion every 8 weeks (±1 week) for a maximum of 6 cycles if participants benefit from the treatment. All participants in this study may undergo dose modification based on the assessment of safety or efficacy by the investigators. Any adverse events (AEs) observed or reported will be recorded. Blood and urine samples will be collected after the first administration of TRC003 on 6 participants in each cohort for pharmacokinetics (blood concentration of TRC003). 2 eligible participants of each cohort (total 6 participants) will undergo SPECT/CT for dosimetry after informed consent. All participants will be assessed PSA every 4 weeks. CT with contrast /MRI and bone scan will be evaluated every 8 weeks until proved disease progression by RECIST version 1.1 and the Prostate Cancer Clinical Trials Working Group 3 (PCWG3).
Interventions
TRC003 is a radioligand therapeutic agent indicated for the treatment of adult patients with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer. TRC003 is a 225Ac-labeled novel molecule for targeted alpha therapy (TAT), which delivers alpha-particle radiation specifically to prostate cancer cells expressing PSMA. Inside the body, it attaches itself to PSMA on the cell surface of the prostate cancer cells and emits radiation to kill them.
Sponsors
C Ray Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have the ability to understand and sign ICF. * Participants must have histological, and/or cytological confirmation of adenocarcinoma of the prostate. * Participants must have progressive mCRPC after treatment of ARPI or taxane-based chemotherapy. * Participant must have been diagnosed with mCRPC with documented progressive disease. * Participants must have prior orchiectomy and/or ongoing androgen-deprivation therapy with a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L). * Participants must have one or more PSMA-positive lesions whose PSMA uptake (SUVmax) is more than 2 fold of the blood pool. * Participants with an ECOG performance status of 0 - 2. * Participants must have adequate organ function * For participants who have partners of childbearing potential: Partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal Investigator during the study and for 6 months after last investigational product administration.
Exclusion criteria
* Participants with mixed histology of prostate cancer (e.g., neuroendocrine). * Any FDG-positive and PSMA-negative target lesions. * Any investigational agents and other concurrent chemotherapy, targeted therapy, biologic agents, immunotherapy, radioligand therapy (androgen-deprivation therapy excepted) within 28 days or 5 half-lives prior to day of administration, whichever is longer. * Previous treatment with any conventional external beam radiotherapy including hemi-body radiation within 6 weeks before enrollment. * Previous bone-targeted therapy cannot be taken with a stable dose within 4 weeks before enrollment. * Known hypersensitivity to the components of the study therapy or its analogs. * Transfusion for the sole purpose of making a participant eligible for study inclusion within 28 days before administration. * A superscan as seen in the baseline bone scan. * Concurrent serious (as determined by the Investigator) medical conditions. * Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of AEs and SAEs | From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months. | Adverse events (AEs) will be assessed and graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) by monitoring adverse events, laboratory tests, vital signs, Electrocardiogram(ECG). |
| Prostate Specific Antigen response (PSA50) | About 12 months. | The percentage of participants who achieved ≥ 50% decrease from baseline at 12 weeks after the first administration or later. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak concentration (Cmax) | 10 days following the first dose. | The maximum measured concentration of TRC003 in the body after administration. |
| AUC0-t | 10 days following the first dose. | Area under the concentration-time curve from time 0 to the last measurable concentration |
| T1/2 | 10 days following the first dose. | Time required for the drug concentration to decrease by 50%. |
| Absorbed dose coefficients | 10 days following the first dose. | The ratio of absorbed dose in a target tissue to the total activity injected, representing dose delivered per unit activity. |
| Residence time | 10 days following the first dose. | The total time that TRC003 remains in a target organ or the body. |
| Effective dose | 10 days following the first dose. | Effective dose is the total radiation dose adjusted for organ sensitivity, used to estimate the risk of radiation-induced health effects. |
| Prostate Specific Antigen response (PSA90) | About 12 months. | The percentage of participants who achieved ≥ 90% decrease from baseline at 12 weeks after the first administration or later |
| Biochemical Progression Free Survival (bPFS) | About 12 months. | Time to PSA progression by PCWG3 criteria (after decline from baseline: record time from start of therapy to first PSA increase that is ≥ 25% and ≥ 2 ng/mL above the nadir, and which is confirmed by a second value ≥ 3 weeks later). |
| Overall Response Rate (ORR) | About 12 months | The proportion of participants with Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) from baseline until radiographic progression or death, whichever comes first. |
| Disease Control Rate (DCR) | About 12 months. | The proportion of participants with BOR of confirmed CR, PR, Stable Disease (SD) or non-CR/non-progressive disease (PD) from baseline until radiographic progression or death, whichever comes first. |
| Duration of Response (DoR) | About 12 months. | Time between the date of first documented response and the date of first documented radiographic progression or death due to any cause by RECIST v1.1 and PCWG3 criteria. |
| Time to first radiographic Soft Tissue Progression (TTSTP) | About 12 months. | Time to radiographic soft tissue progression by RECIST v1.1 and PCWG3 criteria. |
| Time to Progression (TTP) | About 12 months. | Time to the first documented radiographic progression by RECIST v1.1 and PCWG3 criteria. |
| Time to first Symptomatic Skeletal Event (TTSSE) | About 12 months. | Time to the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first. |
| European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | About 12 months. | A qusetionnaire to assess health-related quality of life (HRQOL) in cancer patients by patient-reported outcome (PRO) measure. The standard range of EORTC QLQ-C30 is 0-100 points. For Functional Scales, higher score means better function, better health status, higher quality of life. For Symptom Scales \& Single Symptom Items, higher score means more severe symptoms / greater burden. |
| Functional Assessment of Cancer Therapy - Prostate (FACT-P) | About 12 months. | A disease-specific, patient-reported outcome (PRO) questionnaire designed to measure health-related quality of life (HRQoL) in men with prostate cancer. FACT-P Total Score range is 0-160. Higher score means better quality of life, fewer symptoms, better functional status. |
| Brief Pain Inventory - Short Form (BPI-SF) | About 12 months. | A widely used, validated patient-reported outcome (PRO) tool designed to assess the severity of pain and the impact of pain on daily functioning. BPI-SF Total Score range is 0-110. Higher total score means worse overall pain and greater pain interference with daily life. |
Countries
China
Contacts
CONTACTJihong Liu, PhD
CONTACTYan Wu, MD
STUDY_DIRECTORYan Wu, MD
C Ray Therapeutics (Chengdu) Co., Ltd.
STUDY_CHAIRDingwei Ye, MD, PhD
Fudan University Shanghai Cancer Center, Fudan University
STUDY_CHAIRNianzeng Xing, MD, PhD
Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed