Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Immune System Diseases

Prostatic Neoplasms

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Neuroprotective Agents

Dexamethasone

Hormones

Docetaxel

Prednisolone

Dexamethasone acetate

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

The experimental group start with 6 cycles of induction chemohormonal therapy followed with cytoreductive prostatectomy and postoperative adjuvant radiotherapy if needed. All patients continued maintenance therapy.

The control group start with 6 cycles of chemohormonal therapy followed by continued maintenance therapy.

Under continuous ADT, docetaxel 75mg/m\^2 body surface area every 21 days, oral dexamethasone 7.5mg pretreatment 12h, 3h, 1h before each infusion of docetaxel, and a total of 10mg of prednisolone per day when needed according to the decision of the researcher (in the case of grade 3 and above neutropenia or peripheral edema); oral darolutamide 600mg twice per day, 21 days for one cycle, six cycles in total.

Systemic Chemohormonal Therapy

Under continuous ADT, oral darolutamide 600mg twice per day

Systemic Hormonal Therapy

Cytoreductive prostatectomy was performed after six cycles of neoadjuvant systemic chemohormonal therapy.

Cytoreductive Prostatectomy

Postoperative adjuvant radiotherapy of prostate bed is performed, if margin positive, with conventional segmentation and the dose of 64-72Gy.

Postoperative Adjuvant Radiotherapy

Liang Dong

Liang Dong, Dr.

Yinjie Zhu, Dr.

Ruohua Chen, Dr.

Xinxing Du, Dr.

Yanhao Dong, Dr.

Hanjing Zhu

The goal of this clinical trial is to compare systemic therapy combined with cytoreductive prostatectomy with standard of care (SOC) in de novo poly-metastatic hormone sensitive prostate cancer (de novo pmHSPC). The main questions it aims to answer are:

1. To explore the clinical benefit and safety of systemic therapy combined with cytoreductive prostatectomy for patients with de novo pmHSPC.
2. To explore the characteristics of the subgroup of patients who could benefit more from the above treatment.
3. To explore the relationship between stage efficacy and clinical prognosis.
4. To explore the correlation between molecular imaging such as PSMA-PET/CT and its changes with treatment efficacy.

Participants will undergo systemic therapy combined with cytoreductive prostatectomy.

Researchers will compare systemic therapy combined with cytoreductive prostatectomy with SOC to see the pros and cons of the two strategies.

1. Subject Management

1. Recruitment of subjects The subjects are recruited from the outpatient clinic of the Department of Urology of Renji Hospital, Shanghai Jiao Tong University School of Medicine; the specific time was from the beginning of the recruitment of subjects to the end of reaching the target of the recruitment of subjects. If the attending physician's initial judgment meets the criteria for NAC, recruitment will be carried out after communicating with the patient and his/her family.
2. Informed consent process After the attending physician (investigator) finds patients who initially meet the enrollment criteria of this trial, he/she should give a written and verbal explanation to the subjects about the background, nature, significance, steps, benefits, risks, compensation, injury compensation, and withdrawal of the study, and he/she must obtain an informed consent form signed by each subject (or subject's legal representative). The informed consent form is dated, and the informed consent form and its copy are kept separately by the investigator and the subject.
3. Checking the enrollment criteria As soon as possible after the preliminary identification of subjects, the attending physician and the investigator will check the enrollment criteria together, make a formal decision to recruit or not to recruit into the group and inform the subjects, and explain the reasons for not recruiting into the group in detail and record them.
4. Examination of medical history and records of combined medications During the initial screening and verification of the enrollment criteria, the attending physician will obtain the subject's past history, current medical history, personal history, as well as comorbid medications, and previous medications. If necessary, the history and co-medication records will be declared by the patient himself/herself or under the supervision of the attending physician while signing the informed consent form.
5. Assignment of screening number At the time of signing the informed consent, each patient is assigned a screening number, the rules for the preparation of the screening number are specified separately, and should ensure the principles of continuity, traceability and de-specialization.
6. Assignment of treatment/randomization group numbers Sequence generation: the data manager should use SAS statistical software (SAS Institute. Cary, NC, USA) to generate the allocation sequence in a stratified block randomization with block length set to 4. All subjects were randomly (1:1) assigned to trial and control groups. Factors for stratification included tumor stage (M1a/M1b/M1c) and baseline alkaline phosphatase level (greater/less than ULN). Randomized assignment sequences were performed using sequentially coded sequestration, and interventions should in principle be assigned as soon as possible after generation of the randomized assignment sequence. Sequences should not be accessed by anyone other than the restricted data manager prior to allocation of the intervention.

   Implementation: Generation of the randomized allocation sequence and allocation of the intervention by the data manager, and the generation of the sequence and the allocation of the intervention should be performed by different managers; recruitment of subjects by the attending clinical physician (investigator).
7. Trial Adherence Management During the course of the trial, patients' adherence to the trial will be examined and documented by the supervising physician at each visit and as deemed necessary by the investigator. If necessary, subjects may be instructed to complete a medication diary, which will be checked by the supervising physician and the investigator at each visit. Adherence reports are submitted to the Ombudsman for review as deemed necessary.

2. Intervention Trial group: Systemic therapy plus cytoreductive prostatectomy Control group: Standard of care.

3. Efficacy measurement Efficacy measurements of the specified items and frequencies are performed according to the visit requirements, and the efficacy is observed and recognized strictly according to the criteria set out in the outcomes, and the investigators and evaluators should form an efficacy report and include it in the case report form. PET-CT and PSMA-PET/CT examinations were for the exploratory purpose of this study, so they could be performed on a voluntary basis at the subjects' own expense and with their fully informed consent. The performance or failure of the examination and its results should not affect the performance of other treatments, nor should it affect the performance of other visits and programs.

In order to ensure the objectivity and comparability of the assessment of outcome indicators, the grouping information was hidden from the imaging evaluators and laboratory technicians, and for the scale-based visits, the patient self-assessment was used as the primary method, supplemented by the evaluation under the guidance of the professional staff, and the grouping information was hidden from the supervisory staff when the latter method was used.

4. Data Management

1. Data entry The investigator loads the data into the case report form in a timely, complete, correct and legible manner based on the subject's original observation record. The questionnaire after review and signature by the supervisor should be sent to the Clinical Research Data Manager in a timely manner. The entry is done using the appropriate database system of two-person dual-machine entry, after which the database is compared twice, during which if any problems are found, the supervisor is promptly notified and the researcher is asked to make an answer. The exchange of all kinds of questions and answers between them should be in the form of a questionnaire, which should be kept for reference.
2. Content and manner of data verification and management When all the case report forms have been double-entered and checked for accuracy, a database check report will be written by the data manager, which will include study completion (including list of dislodged subjects), inclusion/exclusion criteria check, completeness check, logical consistency check, outlier data check, time-window check, combined medication check, and adverse event check. At the audit meeting, the principal investigator, representatives of the sponsor, supervisors, data managers and statisticians will make a resolution on the issues raised in the subjects' signing of the informed consent form and the database checking report, write an audit report, and the database will be locked at the same time.
3. Data archiving The case report form, after data entry and verification are completed as required, will be filed and stored in numbered order and filled with search catalogs, etc., for examination. Electronic data files including databases, examination procedures, analytical procedures, analytical results, codebooks and description documents should be classified and kept with multiple backups on different disks or recording media for proper preservation and prevention of damage. All original files should be kept for the period within the corresponding regulations.

5. Analysis and statistical methods Before the start and after the end of each phase of the trial and the trial, the principal investigator, representatives of the sponsor, supervisors, data administrators and statisticians should carry out internal data analysis, including the completion of the study (including the list of dislodged subjects), analysis of the efficacy of the phase, and analysis of the adverse events, etc., and submit the analysis report to the review meeting for consideration.

According to the basic principle of Intention-to-Treat (ITT), the analysis of the main indicators should include all randomized subjects, regardless of whether they completed the trial or not. Therefore, this study used the full analysis set for analysis; when choosing the full analysis set for statistical analysis, the missing of the main indicators should be avoided as much as possible, and when the indicators are indeed missing, the deletion and the reason for deletion should be indicated in the analysis, and the mixed-effects model of repeated-measures data should be applied in the statistical analysis for processing.

Statistical analyses included stage efficacy analyses and summative efficacy analyses. Stage analysis was conducted after all subjects had completed the induction/chemotherapy phase and after all subjects in the trial group had completed the topical treatment phase. Terminal statistical analysis was conducted after all subjects had reached the primary endpoint of the study or had completed 3 years or had been discontinued/withdrawn, i.e., had completed the maintenance phase, and the trial had been completed. Statistical analyses were conducted to determine the relationship between subjects' achievement of the primary and secondary trial endpoints at each stage, and the stage-specific changes in each of the visits associated with the trial endpoints, and their potential impact on factors including, but not limited to, baseline status, receipt of the intervention, and changes in other visits. Statistical analyses were performed according to the following specifications:

Statistical descriptions of patients' baseline clinical characteristics; hypothesis testing for outcomes that manifested as categorical variables and those that manifested as ordered categorical variables using chi-square, Fisher's exact test, and rank-sum tests, as necessary; analysis of outcome indicators of a survival nature using Kaplan-Meier survival analysis; and exploration of the influence of each potentially influencing factor on the outcome using univariate and multivariate Cox regression. The impact of potential influences on outcomes was explored using univariate and multivariate Cox regression.

CytoREductive prostAtectomy for Poly-metastatic Hormone sensiTIVE Prostate Cancer

Systemic Therapy Combined With Cytoreductive Prostatectomy for the Treatment of de Novo Poly-metastatic Hormone Sensitive Prostate Cancer: A Prospective, Open-label Randomized Controlled Trial

From date of randomization to the date of the following events, whichever occurs first: prostate specific antigen (PSA) elevation above nadir of at least 2 ng/mL or elevation above nadir of at least 25% when testosterone is at castration level (\<50 ng/dL), as determined by reassessment at least 3 weeks later; or soft tissue, visceral, or radiographic progression of skeletal lesions: as recommended by the Prostate Cancer Clinical Trials Working Group (PCWG)3, Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 is applied via magnetic resonance imaging (MRI) of the thorax/abdomen/pelvis to determine radiographic progression of soft tissue/visceral lesions; bone metastases are identified separately from soft tissue/visceral metastases and are determined by 99mTc methylenediphosphonate bone scanning of the whole body according to PCWG3. Metastases may also be identified using PSMA-PET/CT.

From date of randomization until the date of death from any cause.

Complete remission is defined as PSA detectable (≥0.2 ng/mL) at baseline and undetectable (\<0.2 ng/mL) for the duration of the study; PSA50, and PSA90 response are defined as a ≥50% or ≥90% decrease in the measured PSA level from baseline to post-baseline as determined by reassessment after at least 3 weeks.

Defined as external radiation therapy for the relief of skeletal symptoms, a new symptomatic pathologic fracture or vertebral compression fracture or related orthopedic surgical intervention, or death, whichever occurred first.

Pain is assessed at each visit using the Visual Analogue Scale (VAS). Pain progression is defined as an increase of ≥2 points from the nadir of the worst pain score or opioid use for more than 7 consecutive days in two consecutive assessments ≥4 weeks apart for asymptomatic patients ("worst pain in 24 hours" score of 0 at baseline). For symptomatic patients (worst pain in 24 hours" score \>0 at baseline), pain progression was defined as an increase of ≥2 points from the nadir of the worst pain score on two consecutive assessments ≥4 weeks apart and with a worst pain score of ≥4 or or initiation of short-acting or long-acting opioid therapy for cancer pain for more than 7 consecutive days.

According to the National Comprehensive Cancer Network/Functional Assessment of Cancer Care Prostate Cancer Symptom Index 17-item questionnaire (NCCN-FACT FPSI-17), worsening of disease-related somatic symptoms was defined as a 3-point decrease in the Disease-related Somatic Symptoms subscale (FPSI-DRS-P subscale) from baseline on two consecutive assessments ≥4 weeks apart.

RenJi Hospital

Associate Research Fellow

Androgen Antagonists

Androgens

Hormone Antagonists

Triplet or doublet therapy followed by cytoreductive prostatectomy or brachytherapy

Triplet or doublet therapy (ie. docetaxel/abiraterone, apalutamide，Rezvilutamide，darolutamide，enzalutamide)

local treatment+SOC for metastatic prostate cancer

Cytoreductive prostatectomy or brachytherapy

SOC(Triplet or doublet therapy) for mHSPC

ADT+second-generation antiandrogens ± chemotherapy

Lixin Hua, M.D.

Shangqian Wang, M.D.,PhD

Shangqian Wang, M.D.

To evaluate: The radiographic progression-free survival (rPFS) of metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with androgen deprivation therapy (ADT) + second-generation antiandrogens±chemotherapy combined with cytoreductive prostatectomy (CRP)

To investigate the multimodality approaches for mHSPC

Cytoreductive Prostatectomy Combined With Triple or Dual Systemic Therapy in mHSPC Patients

Evaluating the Efficacy and Safety of Cytoreductive Prostatectomy Combined With Triple or Dual Systemic Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer

Assess how long a cancer patient lives without any signs of progression of their disease, as determined by radiographic evidence

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CytoREductive prostAtectomy for Poly-metastatic Hormone sensiTIVE Prostate Cancer	NCT06306612	Prostate Cancer	Systemic Chemoh... Systemic Hormon... Cytoreductive P... Postoperative A...	18 Years - 85 Years	RenJi Hospital
Cytoreductive Prostatectomy Combined With Triple or Dual Systemic Therapy in mHSPC Patients	NCT06350825	Metastatic Pros... Therapy, Direct...	Cytoreductive p... ADT+second-gene...	18 Years - 75 Years	The First Affiliated Hospital with Nanjing Medical University
Cytoreductive Prostatectomy Combined With Triple or Dual Systemic Therapy in mHSPC Patients	NCT06350825	Metastatic Pros... Therapy, Direct...	Cytoreductive p... ADT+second-gene...	18 Years - 75 Years	The First Affiliated Hospital with Nanjing Medical University
Cytoreductive Prostatectomy Combined With Triple or Dual Systemic Therapy in mHSPC Patients	NCT06350825	Metastatic Pros... Therapy, Direct...	Cytoreductive p... ADT+second-gene...	18 Years - 75 Years	The First Affiliated Hospital with Nanjing Medical University

Spots Global Cancer Trial Database for cytoreductive prostatectomy