AzTrials
AzTrials

Prostate CancerPhase 2NCT06505278

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

A Phase 2 study testing Receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide in the evening in people with Prostate Cancer, run by Sun Yat-sen University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 75 years, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide in the evening
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteChina
Study dates
Aug 2024to Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Yonghong Li, M.D. contact

13711376697

liyongh@sysucc.org.cn

Jun Wang, M.D. contact

13631448801

wangjun2@sysucc.org.cn

China1 site

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

Other trials in China

About this study

Official title: 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.

Read the 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
Being tested
Receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide in the evening
Keywords
Circadian Rhythm, Metastatic Hormone-Sensitive Prostate Cancer, Medication Timing, Novel Hormonal Therapy
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide in the eveningDrug

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

Study groups in NCT06505278
Study groupRoleWhat they receive
Night medication groupExperimentalParticipants receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide between 10:00 pm and 12:00 pm.
Receives: Drug: Receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide in the evening
Daytime medication groupNo interventionParticipants receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide between 7:00 am and 9:00 am.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    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.

    Measured: Baseline and Week 12

Secondary outcomes (9)

  1. 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

    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.

    Measured: Baseline and Week 12

  2. Clinical benefit rate (CBR) defiend as the proportion of patients comfirming partial response (PR), complete response (CR), or stable disease (SD).

    Clinical benefit refers to participants achieving PR, CR, or SD.

    Measured: Through study completion, an average of 18 months

  3. Objective response rate (ORR) defiend as the proportion of participants confirming partial response (PR) or complete response (CR)

    Objective response refers to participants achieving PR or CR, which would be confirmed 4 weeks later.

    Measured: Through study completion, an average of 18 months

  4. Duration of relief defiend from the first assessment of complete response (CR) or partial response (PR) until the detection of disease progression (PD)

    Duration of relief represents the length of time the tumor remains reduced under this treatment regimen.

    Measured: From CR or PR to PD, up to 18 months

  5. Time to achieve objective relief defiend from randomization until achieving complete response (CR) or partial response (PR).

    Time to achieve objective relief is an important indicator of therapeutic efficacy.

    Measured: From start of treatment to CR or PR, up to 18 months

  6. Time to PSA progression defiend the time from detection of PSA nadir to PSA progression

    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.

    Measured: From start of treatment to PSA progression, up to 18 months

  7. Radiographic progression-free survival (rPFS) defiend from randomization until radiographic progression according to RECIST 1.1 criteria

    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.

    Measured: From start of treatment to radiographic progression, up to 18 months

  8. Overall survival defined from randomization until death from any cause.

    Time to death refers to the time from randomization to death from any cause, which is a crucial indicator for treatment efficacy.

    Measured: From start of treatment to death from any cause, up to 18 months

  9. Treatment emerged adverse event (TEAE)

    Treatment emerged adverse event would be assessed by NCI-CTCAE 5.0.

    Measured: Throughout the entire study period，an average of 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2024
  2. Study startAug 2024 (estimated)
  3. Primary completionMar 2025 (estimated)
  4. Study completionDec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06505278
Sponsor's protocol ID
2023-FXY-183
Status last verified
Aug 2024
First submitted
23 Jun 2024
Last updated
5 Aug 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

    PubMed 30207593

  • Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.

    PubMed 26808342

  • Mottet N, Cornford P, Vanden Bergh RCN, et al. EAU-EANM-ESTRO-ESUR-ISUP_SIOG guidelines on prostate cancer. (2023).

  • Schaeffer EM, Srinivas S, Adra N, An Y, Barocas D, Bitting R, Bryce A, Chapin B, Cheng HH, D'Amico AV, Desai N, Dorff T, Eastham JA, Farrington TA, Gao X, Gupta S, Guzzo T, Ippolito JE, Kuettel MR, Lang JM, Lotan T, McKay RR, Morgan T, Netto G, Pow-Sang JM, Reiter R, Roach M, Robin T, Rosenfeld S, Shabsigh A, Spratt D, Teply BA, Tward J, Valicenti R, Wong JK, Shead DA, Snedeker J, Freedman-Cass DA. Prostate Cancer, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023 Oct;21(10):1067-1096. doi: 10.6004/jnccn.2023.0050.

    PubMed 37856213

  • Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE; COU-AA-302 Investigators. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015 Feb;16(2):152-60. doi: 10.1016/S1470-2045(14)71205-7. Epub 2015 Jan 16.

    PubMed 25601341

  • Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, Davis ID, de Bono JS, Evans CP, Fizazi K, Joshua AM, Kim CS, Kimura G, Mainwaring P, Mansbach H, Miller K, Noonberg SB, Perabo F, Phung D, Saad F, Scher HI, Taplin ME, Venner PM, Tombal B; PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014 Jul 31;371(5):424-33. doi: 10.1056/NEJMoa1405095. Epub 2014 Jun 1.

    PubMed 24881730

  • Zhou T, Zeng SX, Ye DW, Wei Q, Zhang X, Huang YR, Ye ZQ, Yang Y, Zhang W, Tian Y, Zhou FJ, Jie J, Chen SP, Sun Y, Xie LP, Yao X, Na YQ, Sun YH. A multicenter, randomized clinical trial comparing the three-weekly docetaxel regimen plus prednisone versus mitoxantone plus prednisone for Chinese patients with metastatic castration refractory prostate cancer. PLoS One. 2015 Jan 27;10(1):e0117002. doi: 10.1371/journal.pone.0117002. eCollection 2015.

    PubMed 25625938

  • Ozturk N, Ozturk D, Kavakli IH, Okyar A. Molecular Aspects of Circadian Pharmacology and Relevance for Cancer Chronotherapy. Int J Mol Sci. 2017 Oct 17;18(10):2168. doi: 10.3390/ijms18102168.

    PubMed 29039812

  • Patke A, Young MW, Axelrod S. Molecular mechanisms and physiological importance of circadian rhythms. Nat Rev Mol Cell Biol. 2020 Feb;21(2):67-84. doi: 10.1038/s41580-019-0179-2. Epub 2019 Nov 25.

    PubMed 31768006

  • Rosenwasser AM, Turek FW. Neurobiology of Circadian Rhythm Regulation. Sleep Med Clin. 2015 Dec;10(4):403-12. doi: 10.1016/j.jsmc.2015.08.003. Epub 2015 Sep 11.

    PubMed 26568118

  • Hastings MH, Maywood ES, Brancaccio M. Generation of circadian rhythms in the suprachiasmatic nucleus. Nat Rev Neurosci. 2018 Aug;19(8):453-469. doi: 10.1038/s41583-018-0026-z.

    PubMed 29934559

  • Turcu AF, Zhao L, Chen X, Yang R, Rege J, Rainey WE, Veldhuis JD, Auchus RJ. Circadian rhythms of 11-oxygenated C19 steroids and ∆5-steroid sulfates in healthy men. Eur J Endocrinol. 2021 Aug 27;185(4):K1-K6. doi: 10.1530/EJE-21-0348.

    PubMed 34324429

  • Rivard GE, Infante-Rivard C, Hoyoux C, Champagne J. Maintenance chemotherapy for childhood acute lymphoblastic leukaemia: better in the evening. Lancet. 1985 Dec 7;2(8467):1264-6. doi: 10.1016/s0140-6736(85)91551-x.

    PubMed 2866334

  • Rivard GE, Infante-Rivard C, Dresse MF, Leclerc JM, Champagne J. Circadian time-dependent response of childhood lymphoblastic leukemia to chemotherapy: a long-term follow-up study of survival. Chronobiol Int. 1993 Jun;10(3):201-4. doi: 10.3109/07420529309073888.

    PubMed 8319318

  • Qian DC, Kleber T, Brammer B, Xu KM, Switchenko JM, Janopaul-Naylor JR, Zhong J, Yushak ML, Harvey RD, Paulos CM, Lawson DH, Khan MK, Kudchadkar RR, Buchwald ZS. Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal study. Lancet Oncol. 2021 Dec;22(12):1777-1786. doi: 10.1016/S1470-2045(21)00546-5. Epub 2021 Nov 12.

    PubMed 34780711

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Receive Abiraterone plus prednisone/Enzalutamide/Apalutamide/Rezvilutamide in the evening in people with Prostate Cancer, run by Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 5 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Yonghong Li, M.D. (13711376697, liyongh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06505278, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in