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

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

NCT ID: NCT06505278

Condition: Prostate Cancer

Conditions: Official terms:
Prostatic Neoplasms
Prednisone

Conditions: Keywords:
Circadian Rhythm
Metastatic Hormone-Sensitive Prostate Cancer
Medication Timing
Novel Hormonal Therapy

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide in the evening
Description: Participants receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide between 10:00 pm and 12:00 pm in the evening.
Arm group label: Night medication group

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.

Criteria for eligibility:
Criteria:
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.

Gender: Male

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Sun Yat-sen University Cancer Center

Address:
City: Guangzhou
Zip: 510060
Country: China

Start date: August 2024

Completion date: December 2025

Lead sponsor:
Agency: Sun Yat-sen University
Agency class: Other

Source: Sun Yat-sen University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06505278