A Study to Learn How Well a Combination of Darolutamide and Androgen Deprivation Therapy (ADT) Works as a Treatment Before Surgery for Men Who Have High-risk Localized Prostate Cancer.

Official title

CHINANEO: A China Phase 2, Open-Label, Randomized, Multicenter Study to Investigate the Efficacy and Safety of Darolutamide + ADT as Neo-Adjuvant Treatment for 12 Weeks vs 24 Weeks in Treatment-Naïve Participants Who Have Planned for Radical Prostatectomy (RP) With High-Risk Localized Prostate Cancer

Overview

Researchers are looking for a better way to treat men who have high-risk localized prostate cancer, which refers to a type of prostate cancer that is still confined to the prostate gland but has certain characteristics that make it more likely to grow and spread. The study treatment darolutamide plus androgen deprivation therapy (ADT) is under development as treatment before surgery for men who have high-risk localized prostate cancer. Darolutamide works by blocking the attachment of androgen hormones to androgen receptors in cancer cells, thereby blocking cancer progression and growth. ADT is an established treatment that is used to lower the amount of androgen hormones (e.g., testosterone) in the body. The main purpose of this study is to learn how the cancer responds to the two different treatment durations (12 weeks or 24 weeks) of darolutamide combined with ADT used before the men undergo surgery to remove the prostate. For this, the researchers will compare the percentage of participants who either achieve complete response to the treatment (where no cancer cells are found) or with condition of minimal residual disease after the treatment (where only a small amount of cancer cells remains). The study participants will be randomly (by chance) assigned to one of two treatment groups. Depending on the group, they will receive darolutamide tablets by mouth plus ADT administered under the skin for either 12 weeks or 24 weeks. No more than 30 days after the end of the treatments, study participants will be performed with surgery to remove the prostate. Each participant will be in the study for approximately 29 to 32 months, including a screening phase of up to 28 days, 12 weeks or 24 weeks of treatment depending on the treatment groups, followed by the surgery no more than 30 days after the treatment, and a follow up phase of up to 2 years after the surgery. 2 visits to the study site are planned during the screening phase, followed by 3 to 6 visits (every 28 days) during treatment. The treatment period ends with a visit within 7 days after the last dose of treatment. During the study, the doctors and their study team will: * take blood and urine samples * check the participants' health parameters * do physical examinations * check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and, if needed, bone scan * take tumor samples * ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments. About 30 days after the last dose of treatment, 5 weeks after the surgery and every 12 weeks thereafter, the study doctors and their team will check the participants' health and any changes in cancer. This follow-up period ends 2 years after the surgery.

Interventions

• Drug Darolutamide
  Oral tablets of 600 mg twice daily (BID).
• Drug ADT
  Goserelin acetate implant (ZOLADEX), at a dose of 10.8 mg, will be administered subcutaneously every 12 weeks into the anterior abdominal wall below the navel line.

Primary outcome measures

• The proportion of participants achieving pathologic response rate (pRR: pathologic complete response [pCR] or minimal residual disease [MRD]) [Time frame: Completion of Follow-up 1, 30 days after last dose of study drug]

Secondary outcome measures (6)

• Proportion of participants with pathologic complete response (pCR) [Time frame: Completion of Follow-up 1, 30 days after last dose of study drug]
• Percentage of participants with tumor downstaging (e.g. clinical T3 to pathologic T2) [Time frame: At baseline and immediately after radical prostatectomy]
• Percentage of participants with positive surgical margin (PSM) [Time frame: Immediately after radical prostatectomy]
• Biochemical complete response (CR) rate prior to radical prostatectomy (RP) and at landmark timepoints post-RP [Time frame: At pre-RP, at 5 weeks, 12 weeks post-RP, and every 3 months after that until Year 2 after RP or end of follow up]
• Biochemical recurrent free survival since radical prostatectomy (RP) among participants with prostate-specific antigen (PSA) <0.1 ng/mL after RP [Time frame: From RP to biochemical recurrence or death whichever occurs first, up to 2.5 years]
• Incidence and severity of treatment-emergent adverse events (TEAEs) (including treatment-emergent serious adverse events [TESAEs]) [Time frame: From first dose of study drug up to 30 days after the end of study drug administration]

Eligibility criteria

Inclusion criteria

• Participants must be 18 years or older at the time of signing the informed consent.
• Darolutamide-naïve participants who are with localized prostate adenocarcinoma who plan to receive radical prostatectomy (RP) and defined as high risk with National Comprehensive Cancer Network (NCCN) criteria (version 1.2025).
• No evidence of distant metastasis based on computed tomography (CT), magnetic resonance imaging (MRI), and whole body bone scan (WBBS) within 42 days prior to start of study treatment.
• Candidate for RP with pelvic lymph node dissection (PLND) or extended PLND (ePLND) as per the investigator.
• Participants must have at least one of the following features according to NCCN definition of high-risk:

• Biopsy Gleason score ≥8, and/or
• Prostate-specific antigen (PSA) >20 ng/mL measured during Screening and prior to randomization, or
• Clinical stage ≥ T3a.
• Participants with pelvic lymph node involvement (N1) can be included.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Exclusion criteria

• Prostate cancer with known neuroendocrine (NE) differentiation or small cell features.
• Evidence of metastatic disease. Minimum imaging requirements to exclude metastatic disease are diagnostic quality imaging of the chest, pelvis, and the abdomen (CT or MRI with intravenous \[IV\] contrast), and WBBS. Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion.
• Intolerant to darolutamide or androgen deprivation therapy (ADT) treatment.
• History of

• Loss of consciousness or transient ischemic attack or stroke within 6 months prior to randomization, or
• Significant cardiovascular disease within 6 months prior to randomization.
• Any contraindications for RP.
• Uncontrolled or treatment-resistant hypertension.
• History of another malignancy within 5 years prior to randomization.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 23 centers

• The Second Affiliated Hospital of Anhui Medical University — Hefei
• Cancer Hospital, Chinese Academy of Medical Sciences — Beijing
• Peking University First Hospital - Oncology Department — Beijing
• Fujian Medical University - The First Affiliated Hospital — Fuzhou
• Lanzhou University - The Second Hospital (The Second Clinical Medical College of Lanzhou U — Lanzhou
• The first Affiliated Hospital of Guangzhou Medical University — Guangzhou
• Nanfang Hospital, Southern Medical University — Guangzhou
• The 2nd Hospital of Hebei Medical University — Shijiazhuang
• … and 15 more centers

Identifiers

NCT: NCT07450599 · 22982

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗