Clinical trial NCT06505278: The Impact of Medication Timing Adjustment on the Effect of Novel Hormonal Therapy
Official title: The Impact of Circadian Rhythm-Based Medication Timing Adjustment on the Efficacy and Safety of Novel Hormonal Therapy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Circadian Rhythm
Metastatic Hormone-Sensitive Prostate Cancer
Medication Timing
Novel Hormonal Therapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2024-07-17
Enrollment: 70
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: 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
timeFrame: Baseline and Week 12
measure: Clinical benefit rate (CBR) defiend as the proportion of patients comfirming partial response (PR), complete response (CR), or stable disease (SD).
timeFrame: Through study completion, an average of 18 months
measure: Objective response rate (ORR) defiend as the proportion of participants confirming partial response (PR) or complete response (CR)
timeFrame: Through study completion, an average of 18 months
measure: Duration of relief defiend from the first assessment of complete response (CR) or partial response (PR) until the detection of disease progression (PD)
timeFrame: From CR or PR to PD, up to 18 months
measure: Time to achieve objective relief defiend from randomization until achieving complete response (CR) or partial response (PR).
timeFrame: From start of treatment to CR or PR, up to 18 months
measure: Time to PSA progression defiend the time from detection of PSA nadir to PSA progression
timeFrame: From start of treatment to PSA progression, up to 18 months
measure: Radiographic progression-free survival (rPFS) defiend from randomization until radiographic progression according to RECIST 1.1 criteria
timeFrame: From start of treatment to radiographic progression, up to 18 months
measure: Overall survival defined from randomization until death from any cause.
timeFrame: From start of treatment to death from any cause, up to 18 months
measure: Treatment emerged adverse event (TEAE)
timeFrame: Throughout the entire study period，an average of 18 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yonghong Li, M.D.
role: PRINCIPAL_INVESTIGATOR
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