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

August 1, 2024 updated by: Yonghong Li, Sun Yat-sen University

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Sun Yat-sen University Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Night medication group
Participants receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide between 10:00 pm and 12:00 pm.
Drug: 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.
No Intervention: Daytime medication group
Participants receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide between 7:00 am and 9:00 am.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
Baseline and Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
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).
Time Frame: Through study completion, an average of 18 months
Clinical benefit refers to participants achieving PR, CR, or SD.
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)
Time Frame: Through study completion, an average of 18 months
Objective response refers to participants achieving PR or CR, which would be confirmed 4 weeks later.
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)
Time Frame: 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.
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).
Time Frame: From start of treatment to CR or PR, up to 18 months
Time to achieve objective relief is an important indicator of therapeutic efficacy.
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
Time Frame: 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.
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
Time Frame: 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.
From start of treatment to radiographic progression, up to 18 months
Overall survival defined from randomization until death from any cause.
Time Frame: 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.
From start of treatment to death from any cause, up to 18 months
Treatment emerged adverse event (TEAE)
Time Frame: Throughout the entire study period，an average of 18 months
Treatment emerged adverse event would be assessed by NCI-CTCAE 5.0.
Throughout the entire study period，an average of 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-sen University

Investigators

  • Principal Investigator: Yonghong Li, M.D., Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2024

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

June 23, 2024

First Submitted That Met QC Criteria

July 10, 2024

First Posted (Actual)

July 17, 2024

Study Record Updates

Last Update Posted (Estimated)

August 5, 2024

Last Update Submitted That Met QC Criteria

August 1, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-FXY-183

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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