The Impact of Medication Timing Adjustment on the Effect of Novel Hormonal Therapy

Официальное название

The Impact of Circadian Rhythm-Based Medication Timing Adjustment on the Efficacy and Safety of Novel Hormonal Therapy

Обзор

The purpose of this study is to assess the impact of medication timing adjustment on the effect of novel hormonal therapy (NHT) agents in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The half of the patients will receive NHT agents in the morning, and the other half will receive NHT agents in the evening.

Подробное описание

Metastatic hormone-sensitive prostate cancer (mHSPC) can be treated with androgen deprivation therapy (ADT) plus novel hormonal therapy (NHT) agents such as abiraterone, enzalutamide and apalutamide. However, after a period of treatment, patients inevitably develop resistance to hormonal therapy, progressing to metastatic castration-resistant prostate cancer (mCRPC). Once resistance occurs, treatment options are limited and the prognosis is poor. Therefore, enhancing the efficacy of hormonal therapy and delaying the onset of resistance is currently a focal point of research in advanced prostate cancer.

Androgens are a fundamental basis for the growth, proliferation, and metastasis of prostate cancer cells, exhibiting significant circadian rhythms in their synthesis and secretion. The synthesis of androgens and their products such as androstenedione (A4) and testosterone (T) accelerates in the early morning, peaks around 8:00 AM, then declines, reaching a nadir around 8:00 PM. NHT agents, such as abiraterone, primarily inhibit the synthesis of androgens by blocking the CYP17A1 enzyme, thereby aiming to suppress tumor growth. However, abiraterone is currently administered mainly on an empty stomach in the morning, when androgen and its metabolites have already peaked and been released into the bloodstream. Hence, inhibiting androgen synthesis at this time may not yield optimal effects.

Chronotherapy refers to the administration of therapy in alignment with the circadian rhythms of the patient, tumor, and drug to enhance therapeutic efficacy and reduce adverse reactions. In certain malignancies, research has been conducted to adjust the timing of drug administration based on these circadian characteristics, resulting in improved efficacy and reduced adverse reactions compared to traditional dosing schedules.

However, no study has explored the impact of different timing of NHT agents administration on the therapeutic efficacy and safety currently.

Вмешательства

• Препарат Receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide in the evening
  Participants receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide between 10:00 pm and 12:00 pm in the evening.

Первичные конечные точки

• PSA response rate defiend as the proportion of participants whose prostate specific antigen (PSA) decreases by more than 90% from baseline after three months of treatment [Срок оценки: Baseline and Week 12]

Вторичные конечные точки (9)

• Circulating tumor cell (CTC) clearance rate defiend as the proportion testing negative for circulating tumor cell (CTC) at week 12 in patients with a baseline CTC count of ≥1 [Срок оценки: Baseline and Week 12]
• Clinical benefit rate (CBR) defiend as the proportion of patients comfirming partial response (PR), complete response (CR), or stable disease (SD). [Срок оценки: Through study completion, an average of 18 months]
• Objective response rate (ORR) defiend as the proportion of participants confirming partial response (PR) or complete response (CR) [Срок оценки: Through study completion, an average of 18 months]
• Duration of relief defiend from the first assessment of complete response (CR) or partial response (PR) until the detection of disease progression (PD) [Срок оценки: From CR or PR to PD, up to 18 months]
• Time to achieve objective relief defiend from randomization until achieving complete response (CR) or partial response (PR). [Срок оценки: From start of treatment to CR or PR, up to 18 months]
• Time to PSA progression defiend the time from detection of PSA nadir to PSA progression [Срок оценки: From start of treatment to PSA progression, up to 18 months]
• Radiographic progression-free survival (rPFS) defiend from randomization until radiographic progression according to RECIST 1.1 criteria [Срок оценки: From start of treatment to radiographic progression, up to 18 months]
• Overall survival defined from randomization until death from any cause. [Срок оценки: From start of treatment to death from any cause, up to 18 months]
• Treatment emerged adverse event (TEAE) [Срок оценки: Throughout the entire study period，an average of 18 months]

Критерии участия

Критерии включения

• Patients who voluntarily participate in the study and have signed a written informed consent form (ICF);
• Male patients aged 18 to 75 years (inclusive) at the time of signing the ICF;
• Histologically or cytologically confirmed prostate cancer, without prior novel hormonal therapy (NHT) or chemotherapy;
• Assessed as having metastatic hormone-sensitive prostate cancer (mHSPC), defined as: histologically or cytologically confirmed prostate cancer with distant metastases (beyond regional lymph nodes) detected by bone scan, MRI, CT, PET/CT, or pathological examination, and who have not received hormonal therapy or chemotherapy;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1;
• Normal routine blood count and liver and kidney functions, expected to tolerate treatment for mHSPC;
• Expected survival period ≥ 12 weeks.
• Agreement to sign the ICF.

Критерии исключения

• Patients who do not meet the inclusion criteria;
• Patients currently receiving other systemic anticancer treatments (such as chemotherapy and/or immunotherapy);
• Patients who have undergone organ transplantation within the past three months;
• Patients with active, known, or suspected autoimmune diseases; or those testing positive for hepatitis B virus, hepatitis C virus, or HIV indicating acute or chronic infection;
• Patients with severe life-threatening diseases;
• Patients who have not signed the ICF;
• Other conditions deemed by the researchers to make the patient unsuitable for participation in the trial.

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 · 1 центр

• Sun Yat-sen University Cancer Center — Гуанчжоу

Публикации

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Идентификаторы

NCT: NCT06505278 · 2023-FXY-183

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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