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

NCT ID: NCT06505278

Last Updated: 2024-08-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-31
• Study Completion Date: 2025-12-31

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Night medication group

Participants receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide between 10:00 pm and 12:00 pm.

Group Type: EXPERIMENTAL

Receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide in the evening

Intervention Type: DRUG

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

Daytime medication group

Participants receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide between 7:00 am and 9:00 am.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

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.

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Yonghong Li

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yonghong Li, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Yonghong Li, M.D.

Role: CONTACT

liyongh@sysucc.org.cn

13711376697

Jun Wang, M.D.

Role: CONTACT

wangjun2@sysucc.org.cn

13631448801

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Other Identifiers

2023-FXY-183

Identifier Type: -

Identifier Source: org_study_id