Trial Title:
CytoREductive prostAtectomy for Poly-metastatic Hormone sensiTIVE Prostate Cancer
NCT ID:
NCT06306612
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Systemic Chemohormonal Therapy
Description:
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.
Arm group label:
Control group
Arm group label:
Experimental group
Intervention type:
Drug
Intervention name:
Systemic Hormonal Therapy
Description:
Under continuous ADT, oral darolutamide 600mg twice per day
Arm group label:
Control group
Arm group label:
Experimental group
Intervention type:
Procedure
Intervention name:
Cytoreductive Prostatectomy
Description:
Cytoreductive prostatectomy was performed after six cycles of neoadjuvant systemic
chemohormonal therapy.
Arm group label:
Experimental group
Intervention type:
Procedure
Intervention name:
Postoperative Adjuvant Radiotherapy
Description:
Postoperative adjuvant radiotherapy of prostate bed is performed, if margin positive,
with conventional segmentation and the dose of 64-72Gy.
Arm group label:
Experimental group
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Fully understand the purpose of this trial and sign a written informed consent;
2. Men aged 18-85 years;
3. have histologically or cytologically confirmed adenocarcinoma of the prostate;
4. Have multiple metastatic disease, defined as follows: according to RECIST v1.1,
metastatic disease was defined as metastatic foci detected on bone scans or
measurable lymph nodes or soft tissue or visceral lesions above the aortic
bifurcation. Lymph nodes were defined as measurable if their short-axis diameter was
≥15 mm; soft tissue/visceral lesions were defined as measurable if their long-axis
diameter was ≥10 mm. and total number of metastatic lesions ≥ 5. Patients with only
regional lymph node metastases (N1, below the aortic bifurcation) were not eligible
for the study.
5. At the investigator's discretion, patients must meet the indications for ADT and
docetaxel;
6. Patients have not received any prior local or systemic therapy for prostate cancer
primary or metastasis.
7. Eastern Cooperative Oncology Group (ECOG) score of 0-1;
8. Blood count at screening: hemoglobin ≥ 9.0 g/dL, absolute neutrophil count ≥ 1.5 x
10^9/L, and platelet count ≥ 100 x 10^9/L (patient has not received any
colony-stimulating factor within 4 weeks or a transfusion or blood product within 7
days prior to blood collection)
9. Serum alanine aminotransferase and/or aspartate aminotransferase ≤ 1.5 x Upper limit
of normal (ULN), total bilirubin ≤ ULN, creatinine ≤ 2.0 x ULN.
Exclusion Criteria:
1. Prior therapy: ADT, second-generation androgen receptor inhibitors, CYP17 enzyme
inhibitors, any chemotherapy or immunotherapy for prostate cancer, radiotherapy
(external radiation radiotherapy, brachytherapy, or radiopharmaceuticals);
2. Known hypersensitivity to any of the investigational drugs, or excipients in the
preparations;
3. Contraindication to CT/MRI examination;
4. Any of the following conditions within 6 months prior to randomization: stroke,
myocardial infarction, severe or unstable angina, coronary or peripheral artery
bypass grafting, or congestive heart failure (New York Heart Association cardiac
function class III or IV);
5. uncontrolled hypertension as evidenced by a resting systolic blood pressure ≥ 160 mm
Hg or diastolic blood pressure ≥ 100 mm Hg after treatment
6. History of prior malignancy, except basal cell or cutaneous squamous cell carcinoma
in complete remission;
7. History of gastrointestinal disorders or surgery expected to significantly interfere
with the absorption of study drug(s);
8. Active acute and chronic viral hepatitis, known HIV infection;
9. Prior (28 days prior to initiation of study drug or 5 half-lives of investigational
therapy from a prior study, whichever is longer) or concurrent participation in
another clinical study of study drug;
10. Any other serious or unstable medical condition or condition that may interfere with
their participation in the study or the evaluation of study results or may
jeopardize the safety of the trial and other conditions;
11. Inability to swallow oral medications;
12. A close interest in the research center.
Gender:
Male
Minimum age:
18 Years
Maximum age:
85 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Renji Hospital, Shanghai Jiao Tong University School of Medicine
Address:
City:
Shanghai
Zip:
200127
Country:
China
Status:
Recruiting
Contact:
Last name:
Liang Dong, Dr.
Phone:
+86-13601613536
Email:
drdongliang@126.com
Investigator:
Last name:
Yinjie Zhu, Dr.
Email:
Principal Investigator
Investigator:
Last name:
Liang Dong, Dr.
Email:
Principal Investigator
Investigator:
Last name:
Ruohua Chen, Dr.
Email:
Sub-Investigator
Investigator:
Last name:
Xinxing Du, Dr.
Email:
Sub-Investigator
Investigator:
Last name:
Yanhao Dong, Dr.
Email:
Sub-Investigator
Investigator:
Last name:
Hanjing Zhu
Email:
Sub-Investigator
Start date:
March 21, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
RenJi Hospital
Agency class:
Other
Source:
RenJi Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06306612
