Prostate Cancer
Conditions
Keywords
Circadian Rhythm, Metastatic Hormone-Sensitive Prostate Cancer, Medication Timing, Novel Hormonal Therapy
Brief summary
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.
Detailed description
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.
Interventions
DRUGReceive 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.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline and Week 12 | PSA is a critical indicator for assessing the efficacy of prostate cancer treatment; typically, a lower PSA value suggests better therapeutic outcomes. A second PSA measurement is confirmed after 3 weeks from week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical benefit rate (CBR) defiend as the proportion of patients comfirming partial response (PR), complete response (CR), or stable disease (SD). | Through study completion, an average of 18 months | Clinical benefit refers to participants achieving PR, CR, or SD. |
| Objective response rate (ORR) defiend as the proportion of participants confirming partial response (PR) or complete response (CR) | Through study completion, an average of 18 months | Objective response refers to participants achieving PR or CR, which would be confirmed 4 weeks later. |
| Duration of relief defiend from the first assessment of complete response (CR) or partial response (PR) until the detection of disease progression (PD) | From CR or PR to PD, up to 18 months | Duration of relief represents the length of time the tumor remains reduced under this treatment regimen. |
| Time to achieve objective relief defiend from randomization until achieving complete response (CR) or partial response (PR). | From start of treatment to CR or PR, up to 18 months | Time to achieve objective relief is an important indicator of therapeutic efficacy. |
| 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 | Baseline and Week 12 | CTC are tumor cells that enter the bloodstream and are associated with the metastasis of tumors. Typically, a lower CTC count is indicative of better therapeutic efficacy. |
| Radiographic progression-free survival (rPFS) defiend from randomization until radiographic progression according to RECIST 1.1 criteria | From start of treatment to radiographic progression, up to 18 months | rPFS refers to the time from randomization to radiographic progression defined as tumor progression assessed by CT, MRI, or ECT according to RECIST 1.1 criteria, which is an important indicator for treatment efficacy. |
| Overall survival defined from randomization until death from any cause. | From start of treatment to death from any cause, up to 18 months | Time to death refers to the time from randomization to death from any cause, which is a crucial indicator for treatment efficacy. |
| Treatment emerged adverse event (TEAE) | Throughout the entire study period，an average of 18 months | Treatment emerged adverse event would be assessed by NCI-CTCAE 5.0. |
| Time to PSA progression defiend the time from detection of PSA nadir to PSA progression | From start of treatment to PSA progression, up to 18 months | PSA progression refers to PSA\>1ng/ml, with at least a one-week interval between PSA measurement and two consecutive increases of\>50% compared to the baseline value. |
Countries
China
Contacts
Primary ContactYonghong Li, M.D.
Backup ContactJun Wang, M.D.
Outcome results
None listed