Safety and Efficacy of Docetaxel, Darolutamide, and Homoharringtonine Combined With Androgen Deprivation Therapy in Neoadjuvant Treatment of High-Risk Prostate Cancer: A Multicenter Prospective, Single-Arm Clinical Study

Previous study findings suggest that the efficacy limitations of the neoadjuvant treatment regimen combining docetaxel with androgen deprivation therapy are associated with protein synthesis. Homoharringtonine (HHT) is currently the only small-molecule translation elongation inhibitor approved by the U.S. Food and Drug Administration (FDA). Building on this foundation, we plan to conduct a prospective interventional study aimed at validating whether the intensified quadruple regimen, formed by adding darolutamide and homoharringtonine (HHT) to the standard regimen, can further significantly enhance the depth of pathological response and improve patient outcomes through multi-mechanism synergy.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Docetaxel+ Darolutamide + Homoharringtonine+ Androgen Deprivation Therapy

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Bin Xu; Phone Number: 86+025-83272000; Email: njxbseu@seu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ① Age ≥ 18 years and ≤ 85 years;

  • Histologically or cytologically confirmed prostate cancer;

    • High-risk prostate cancer: meeting at least one of the following criteria: clinical stage T3-T4, or Gleason score 8-10, or PSA > 20 ng/mL, or presence of distant metastasis (clinical stage M1); ④ ECOG (Eastern Cooperative Oncology Group) performance status score of 0-1; ⑤ All patients voluntarily sign informed consent and are able to adhere to treatment and follow-up

Exclusion Criteria:

• ① Any prior or ongoing treatment for prostate cancer, including radiotherapy, chemotherapy, ADT, etc.;

  • Previous prostatectomy; ③ Any other serious underlying medical, psychiatric, or psychological conditions that, in the investigator's judgment, may affect treatment;

    • Allergy to any of the study drugs; ⑤ Refusal to undergo radical prostatectomy; ⑥ Deemed unsuitable for participation in this clinical trial by the investigator's judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment group

Drug: Docetaxel+ Darolutamide + Homoharringtonine+ Androgen Deprivation Therapy; **Docetaxel:** 75 mg/m², intravenous infusion, once every 3 weeks (administered in weeks 1, 4, and 7), for a total of 3 cycles. To prevent allergic reactions and fluid retention, oral dexamethasone 8 mg is administered twice daily on the day before, the day of, and the day after docetaxel infusion. **Darolutamide:** 600 mg, orally, twice daily, starting from day 1 of treatment and continued until 1 week before surgery. To be taken with food. **Homoharringtonine:** 1 mg of homoharringtonine diluted in 250 mL of 5% glucose injection, administered intravenously once daily for two consecutive days, repeated every 3 weeks (administered in weeks 1, 4, and 7), for a total of 3 cycles. **Androgen Deprivation Therapy:** Luteinizing hormone-releasing hormone (LHRH) analogs such as goserelin. The specific dosage is goserelin 3.6 mg, administered as a subcutaneous injection into the anterior abdominal wall once every 28 day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR or MRD Rate	:-**pCR (Pathological Complete Response)** is defined as the absence of morphologically identifiable cancer in the prostatectomy specimen. - **MRD (Minimal Residual Disease)** is defined as a maximum cross-sectional diameter of residual tumor ≤ 5 mm, and using RCB (Residual Cancer Burden) ≤ 0.25 cm³ (tumor volume ≤ 0.5 cm³ × tumor cellularity ≤ 50%). Tumor volume is calculated by three-dimensional volume estimation based on the largest cross-sectional dimension of the tumor and the number of cross-sections, with adjustment for tumor cellularity.	1 month after surgery
PSA response rate		Defined as the comparison of PSA levels before neoadjuvant therapy and at the end of the neoadjuvant therapy cycle (before surgery).
iochemical Progression-Free Survival (bPFS) after Radical Prostatectomy		1 month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological response after radical prostatectomy	Pathological response after radical prostatectomy (including positive surgical margins, tumor size, extraprostatic extension, seminal vesicle invasion, and lymph node involvement)	1 month after surgery
TNM stage	Changes in TNM staging on imaging after neoadjuvant therapy and before surgery	1 month after surgery
Other PFS	Other Progression-Free Survival (progression includes radiographic progression, castration resistance, need for further therapeutic intervention, etc.)	1 month after surgery
Safety indicator: CTCAE 5.0 adverse event grading		1 month after surgery
Quality of life score: EORTC QLQ-C30 questionnaire		1 month after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in prespecified transcriptomic features in tumor tissue before and after neoadjuvant treatment	Change in prespecified transcriptomic features measured in paired tumor tissue samples collected before treatment and at radical prostatectomy, assessed using bulk RNA sequencing and/or single-cell or spatial transcriptomic profiling.	1 month after surgery
Change in prespecified proteomic features in tumor tissue before and after neoadjuvant treatment	Change in prespecified proteomic features measured in paired tumor tissue samples collected before treatment and at radical prostatectomy, assessed using proteomic profiling.	1 month after surgery
Change in prespecified intratumoral microbiome features before and after neoadjuvant treatment	Change in prespecified intratumoral microbiome features measured in paired tumor tissue samples collected before treatment and at radical prostatectomy, including microbial composition, relative abundance of prespecified taxa, and diversity indices.	1 month after surgery
Difference in tumor tissue molecular features between participants who achieve and do not achieve the primary endpoint	Difference in prespecified transcriptomic and proteomic features in tumor tissue between participants who achieve the primary endpoint (pathological complete response or minimal residual disease) and those who do not, assessed using tissue obtained at radical prostatectomy.	1 month after surgery
Change in prespecified liquid biopsy biomarkers before and after neoadjuvant treatment	Change in prespecified liquid biopsy biomarkers measured in blood and/or urine samples collected before treatment and after completion of neoadjuvant therapy, including genomic, proteomic, and metabolomic indicators associated with treatment response.	1 month after surgery

Collaborators and Investigators

• Sponsor: Zhongda Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 12, 2027

Study Registration Dates

• First Submitted: March 25, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 2026ZDSYLL031-P01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No