A Study of TRC003 in the Treatment of Patients With Progressive PSMA-positive mCRPC

Официальное название

A Prospective, Open-label, Randomized, Phase 1/2 Study of TRC003 in the Treatment of Patients With Progressive PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC)

Обзор

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.

Подробное описание

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).

Вмешательства

• Препарат Radiopharmaceuticals
  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.

Первичные конечные точки

• Incidence and severity of AEs and SAEs [Срок оценки: 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.]
• Prostate Specific Antigen response (PSA50) [Срок оценки: About 12 months.]

Вторичные конечные точки (12)

• Peak concentration (Cmax) [Срок оценки: 10 days following the first dose.]
• AUC0-t [Срок оценки: 10 days following the first dose.]
• T1/2 [Срок оценки: 10 days following the first dose.]
• Absorbed dose coefficients [Срок оценки: 10 days following the first dose.]
• Residence time [Срок оценки: 10 days following the first dose.]
• Effective dose [Срок оценки: 10 days following the first dose.]
• Prostate Specific Antigen response (PSA90) [Срок оценки: About 12 months.]
• Biochemical Progression Free Survival (bPFS) [Срок оценки: About 12 months.]
• Overall Response Rate (ORR) [Срок оценки: About 12 months]
• Disease Control Rate (DCR) [Срок оценки: About 12 months.]
• Duration of Response (DoR) [Срок оценки: About 12 months.]
• Time to first radiographic Soft Tissue Progression (TTSTP) [Срок оценки: About 12 months.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Cancer Hospital, Chinese Academy of Medical Sciences, Shanxi Hospital — Taiyuan
• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07567521 · TR1189-2501-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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