Prostate Cancer (Adenocarcinoma)
Conditions
Brief summary
This study will assess the effects and safety of deutenzalutamide combined with hormone therapy before and after prostate cancer surgery, with docetaxel chemotherapy added before surgery. It is intended for men with high-risk localized or locally advanced prostate cancer who have no distant spread on imaging and are suitable for surgery. The researchers will measure how often treatment leaves no cancer or only a very small amount of cancer in the prostate, with no cancer in the pelvic lymph nodes removed during surgery. They will also assess whether participants can undergo the planned surgery, what side effects occur, and whether the cancer returns or spreads during follow-up. Up to 37 participants will be enrolled at several hospitals. All participants will be assigned to the same treatment plan; there is no comparison group. The planned treatment includes: * Deutenzalutamide taken by mouth each day, together with hormone therapy to lower testosterone levels, for 24 weeks before surgery. * Docetaxel given through a vein once every 3 weeks for six cycles during the treatment period before surgery. * Surgery to remove the prostate and pelvic lymph nodes, when medically appropriate. * A further 24 weeks of deutenzalutamide and hormone therapy after recovery from surgery, without further docetaxel. Hormone therapy will continue across the treatment periods for a total of at least 13 months. Treatment may be adjusted or stopped according to side effects and the participant's condition. Follow-up is planned for up to 5 years after all study treatment has ended. Participants may also choose to join an optional study using a single blood sample collected before treatment and leftover tissue from their diagnostic prostate biopsy. These samples will be used to explore features that may be associated with treatment response and later outcomes. Participation in this optional component is not required to receive the study treatment.
Detailed description
POST-PC-01 is an investigator-initiated, prospective, multicenter, single-arm, open-label exploratory study. The rationale is to combine androgen receptor pathway inhibition and androgen deprivation with chemotherapy before definitive surgery, while limiting docetaxel exposure to the preoperative period. The study will generate preliminary evidence on antitumor activity, safety, and clinical feasibility; it is not designed to establish superiority over another treatment. The study uses a Simon minimax two-stage design. The first stage includes 16 participants in the prespecified primary efficacy decision analysis set. Enrollment will proceed to the second stage only if the first-stage results meet the predefined continuation criterion. The second stage adds 15 participants, for a total of 31 participants in the decision analysis set. The maximum enrollment of 37 allows limited replacement under protocol-defined circumstances unrelated to treatment efficacy or tolerability. Participants unable to undergo surgery because of disease progression or treatment toxicity are counted as nonresponders rather than replaced. The optional exploratory component is limited to pretreatment samples. It includes one peripheral blood collection of 20 mL for genetic analysis and the use of residual tissue from the diagnostic prostate biopsy. Tissue assessments include intraductal carcinoma of the prostate, BRCA1 and BRCA2 and other DNA repair-related gene alterations, and PTEN deletion or related abnormalities. No additional biopsy is performed for this component. Where samples and outcome data are available, associations between baseline pathological or genetic features and pathological response, recurrence, or progression will be explored descriptively. Participation requires an affirmative choice within the study informed consent form. Declining or withdrawing from this optional component does not affect participation in the study treatment and follow-up.
Interventions
DRUGDeutenzalutamide
Deutenzalutamide 80 mg is administered orally once daily with androgen deprivation therapy (ADT) for 24 weeks before radical prostatectomy. After adequate postoperative recovery, deutenzalutamide is planned to resume approximately 4 weeks after surgery at the last tolerated dose, with ADT, for an additional 24 weeks. Dose modifications and treatment interruptions are managed according to the protocol.
DRUGDocetaxel
Docetaxel 60 mg/m² is administered by intravenous infusion every 3 weeks for 6 cycles (planned at Weeks 0, 3, 6, 9, 12, and 15) during neoadjuvant treatment, in combination with deutenzalutamide and androgen deprivation therapy (ADT). Treatment interruptions and discontinuation follow protocol-defined criteria; docetaxel is not administered during postoperative adjuvant treatment.
DRUGADT
Androgen deprivation therapy (ADT) is administered according to the prescribing information for the selected agent. Treatment begins in the neoadjuvant phase and continues through the perioperative and postoperative adjuvant phases for a total duration of at least 13 months.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Hinova Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion Criteria: * Men aged 18-80 years with histologically confirmed high-risk localized or locally advanced prostate adenocarcinoma. * High-risk disease is defined by meeting either (1) or (2): 1. NCCN high-risk criteria: at least one of the following:Gleason score \>=8;Prostate-specific antigen (PSA) \>=20 ng/mL;Clinical T stage \>=T3. 2. Study-specific biopsy criteria: overall Gleason score \>=4+3 (International Society of Urological Pathology \[ISUP\] Grade Group \[GG\] 3-5), plus at least one of the following:(a) \>=6 systematic biopsy cores showing Gleason 4+3 (GG3) or Gleason 8 (4+4 or 5+3), including at least one Gleason-8 core. Only systematic cores are counted; targeted cores are excluded from this count;(b) \>=3 systematic biopsy cores showing Gleason 4+3 (GG3) or Gleason 8 (4+4 or 5+3), PSA \>=20 ng/mL, and at least one Gleason-8 core. Only systematic cores are counted; targeted cores are excluded from this count;(c) \>=1 systematic or targeted biopsy core with Gleason score \>=9 (GG5). Both systematic and targeted cores may be counted, without counting the same core more than once;(d) \>=2 distinct, evaluable systematic or targeted biopsy cores, each with Gleason score \>=8 (GG4-5) and tumor involvement \>=80%. Core counting and tumor involvement are determined according to the protocol's standardized rules. * No distant metastases (cM0) on baseline imaging; cN0 or pelvic cN1 below the common iliac artery bifurcation is permitted. Suitable for radical prostatectomy and pelvic lymph node dissection. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy \>=10 years; able to receive androgen-deprivation therapy for \>=13 months. * Adequate organ function, assessed after \>=14 days without blood-component transfusion or hematopoietic support: neutrophils \>=1.5 x 10\^9/L; platelets \>=100 x 10\^9/L; hemoglobin \>=9 g/dL; potassium \>=3.5 mmol/L; ALT and AST \<=2.5 times the upper limit of normal (ULN); total bilirubin \<=1.5 x ULN; creatinine \<1.5 x ULN; albumin \>=3.0 g/dL; international normalized ratio (INR) \<1.5. Eligibility during therapeutic anticoagulation requires investigator assessment. * Able to swallow capsules, without significant swallowing difficulty or a history of severe gastrointestinal malabsorption. * Written informed consent and willingness to comply with study procedures and applicable contraception requirements.
Exclusion criteria
* Neuroendocrine/small-cell prostate carcinoma, distant metastases, or previous local or systemic treatment for prostate cancer. * Allergy to study drugs, excipients or drugs of the same class; contraindications to docetaxel or prednisone acetate, including active infection. * Need for chronic systemic glucocorticoids exceeding a total prednisone-equivalent dose of 10 mg/day during study treatment. * Poorly controlled hypertension despite treatment: systolic \>=160 mmHg or diastolic \>=95 mmHg. * Active or symptomatic viral hepatitis or other chronic liver disease; known HIV infection. * History of pituitary or adrenal dysfunction; active autoimmune disease requiring corticosteroids. * Serious cardiovascular/cerebrovascular disease within 6 months before study treatment, including severe/unstable angina, myocardial infarction, New York Heart Association class III-IV heart failure, stroke, or arrhythmia requiring medication. * Previous allogeneic organ or hematopoietic stem-cell transplantation. * Grade \>=2 peripheral sensory or motor neuropathy. * Another malignancy currently or within the previous 2 years. * Major surgery requiring general anesthesia within 28 days before the first dose. * Use of prohibited urinary-symptom or PSA-altering medications during deutenzalutamide treatment, including finasteride, dutasteride or phytoestrogens. * Seizure history or conditions increasing seizure risk, including stroke within 1 year before the first study anticancer dose or cerebral arteriovenous malformation; benign central nervous system/meningeal disease expected to require surgery or radiotherapy during study treatment. * Alcohol or drug abuse/dependence. * Participation in another therapeutic clinical trial within 1 month before study treatment. * Any other condition considered unsuitable by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response or Minimal Residual Disease (pCR/MRD) Rate | At postoperative pathological assessment (surgery planned approximately 26 weeks after treatment initiation; qualifying surgery within 56 days after the actual end of neoadjuvant treatment). | Percentage of participants in the prespecified primary efficacy decision analysis set who achieve pCR or MRD on pathological examination of radical prostatectomy and pelvic lymph node dissection specimens after neoadjuvant treatment. pCR is defined as no identifiable residual cancer in the prostate (ypT0) and no regional lymph node metastasis (ypN0). MRD is defined as residual cancer confined to the prostate (ypT2 or lower), with the largest residual tumor focus measuring no more than 5 mm in greatest dimension, and ypN0. Both require no confirmed distant metastasis at assessment. Each participant is counted once. Participants unable to undergo surgery within 56 days after the actual end of neoadjuvant treatment because of disease progression, treatment toxicity or intolerance are counted as nonresponders. Other unassessable cases are handled according to the prespecified protocol rules. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metastasis-Free Survival (MFS) | From the first dose of study anticancer treatment to distant metastasis or death, whichever occurs first, with follow-up through 60 months after the end of all study treatment. | Time from the first administration of study anticancer treatment to the first occurrence of distant metastasis confirmed by imaging (PSMA-PET/CT or conventional imaging) or pathology, or death from any cause, whichever occurs first. Distant metastasis includes nonregional lymph node, bone, or visceral metastasis. Regional pelvic lymph node involvement alone is not considered distant metastasis. |
| Event-Free Survival (EFS) | From the first dose of study anticancer treatment to the first qualifying EFS event, with follow-up through 60 months after the end of all study treatment. | Time from the first dose of study anticancer treatment to the earliest of: (1) biochemical failure after radical prostatectomy (RP), defined as serum prostate-specific antigen (PSA) \>=0.2 ng/mL confirmed by another value \>=0.2 ng/mL at least 1 week later; (2) imaging- or pathology-confirmed local or regional recurrence; (3) imaging- or pathology-confirmed distant metastasis; or (4) death from any cause. The event date for biochemical failure is the date of the first qualifying PSA sample, including for confirmed persistent postoperative PSA. Biochemical failure does not require imaging-confirmed recurrence. Preoperative local or regional progression, including progression preventing RP, is not an EFS event; preoperative distant metastasis or death is an event. Positive surgical margins, positive pathological lymph nodes, or failure to achieve pCR/MRD do not automatically constitute EFS events. |
| Time to Distant Metastasis | From the first dose of study anticancer treatment to the first confirmed distant metastasis, with follow-up through 60 months after the end of all study treatment. | Time from the first dose of study anticancer treatment to the first distant metastasis confirmed by imaging (PSMA-PET/CT or conventional imaging) or pathology. Distant metastasis includes nonregional lymph node, bone, or visceral metastasis. Regional pelvic lymph node involvement alone is not considered distant metastasis. Death without prior distant metastasis is not counted as a distant metastasis event. Competing risks are addressed as prespecified in the statistical analysis plan. |
| Time to First Subsequent Anticancer Therapy | From the first dose of study anticancer treatment to initiation of the first subsequent anticancer therapy, with follow-up through 60 months after the end of all study treatment. | Time from the first dose of study anticancer treatment to the initiation of the first subsequent anticancer therapy outside the protocol-defined treatment regimen for prostate cancer recurrence, progression, or other disease-related reasons. Subsequent therapy may include radiotherapy, endocrine therapy, androgen receptor pathway inhibitors, chemotherapy, radionuclide therapy, or other systemic anticancer treatments. Protocol-specified neoadjuvant and adjuvant treatments are not counted as subsequent therapy. Competing risks are addressed as prespecified in the statistical analysis plan. |
| Biochemical Recurrence-Free Survival (bRFS) | From radical prostatectomy to biochemical recurrence or death, whichever occurs first, with follow-up through 60 months after the end of all study treatment. | Time from radical prostatectomy (RP) to the first occurrence of biochemical recurrence (BCR) or death from any cause, whichever occurs first. BCR is defined as postoperative serum prostate-specific antigen (PSA) \>=0.2 ng/mL, confirmed by a subsequent PSA measurement \>=0.2 ng/mL at least 1 week later. The BCR event date is the date of the first qualifying PSA sample. Participants with persistent postoperative PSA \>=0.2 ng/mL also require subsequent confirmation; the event date is the date of the first postoperative sample meeting this threshold, and PSA persistence is recorded separately. Imaging-confirmed recurrence is not required. |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | From the first dose of protocol-specified anticancer treatment through 30 days after the end of all study treatment. | Percentage of participants in the safety analysis set who experience at least one treatment-emergent adverse event (TEAE). A TEAE is an adverse event that first occurs or worsens after the first dose of protocol-specified study treatment during the safety observation period, regardless of its relationship to treatment. Events are coded using MedDRA and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 6.0. Severity and relationship to study treatment are summarized. Safety is assessed across the neoadjuvant, surgical, and adjuvant treatment phases. |
| Percentage of Participants With Grade 3 or Higher Adverse Events | From the first dose of protocol-specified anticancer treatment through 30 days after the end of all study treatment. | Percentage of participants in the safety analysis set who experience at least one Grade 3 or higher adverse event during the safety observation period, regardless of its relationship to study treatment. Severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 6.0. Grade 3 indicates severe events, Grade 4 indicates life-threatening events, and Grade 5 indicates death related to an adverse event. Assessment covers the neoadjuvant, surgical, and adjuvant treatment phases. |
| Incidence and Severity of Postoperative Complications | From radical prostatectomy through the adjuvant baseline visit (approximately 4 weeks postoperatively), with additional assessment at adjuvant Week 4 (approximately 8 weeks postoperatively) as clinically indicated. | Percentage of participants undergoing radical prostatectomy who experience at least one postoperative complication. Complications are summarized by type and severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0, with investigator clinical judgment for events not specifically covered by CTCAE. |
| Percentage of Participants With Serious Adverse Events (SAEs) | From the first dose of protocol-specified anticancer treatment through 30 days after the end of all study treatment. | Percentage of participants in the safety analysis set who experience at least one serious adverse event (SAE) during the safety observation period, regardless of its relationship to study treatment. An SAE is an event that results in death, is life-threatening, requires unplanned hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, causes a congenital anomaly or birth defect, or is another important medical event that may jeopardize the participant or require medical or surgical intervention to prevent such outcomes. Planned hospitalization for radical prostatectomy alone is not considered an SAE; complications requiring unplanned admission, readmission, or prolonged hospitalization are assessed against the SAE criteria. Seriousness is assessed separately from NCI-CTCAE severity grading. |
| Percentage of Participants With Adverse Events Leading to Study Drug Interruption, Dose Modification, or Permanent Discontinuation | From the first dose of protocol-specified anticancer treatment through 30 days after the end of all study treatment. | Percentage of participants in the safety analysis set who experience at least one adverse event leading to temporary interruption, dose modification, or permanent discontinuation of a study drug. For each event, the affected drug, action taken, severity, relationship to treatment, and outcome are recorded. Severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 6.0. Assessment covers the neoadjuvant, surgical, and adjuvant treatment phases. Planned treatment completion or protocol-specified interruptions not caused by an adverse event are not counted. |
| Percentage of Participants With Treatment-Related Deaths | From the first dose of protocol-specified anticancer treatment through 30 days after the end of all study treatment. | Percentage of participants in the safety analysis set who die from an adverse event assessed by the investigator as related to study treatment. Related events include those judged definitely, probably, or possibly related to a protocol-specified study intervention; deaths assessed as unlikely related or unrelated are excluded from this endpoint. |
| Serum Prostate-Specific Antigen (PSA) Level at the End of Neoadjuvant Treatment | At the end of neoadjuvant treatment (planned at Week 24), before radical prostatectomy. | Serum prostate-specific antigen (PSA) concentration is measured in ng/mL at the end of neoadjuvant treatment, before radical prostatectomy. The absolute PSA value at this assessment is summarized using descriptive statistics. |
| Serum Prostate-Specific Antigen (PSA) Levels After Radical Prostatectomy and During Adjuvant Treatment | At adjuvant treatment baseline (approximately 4 weeks after radical prostatectomy) and at adjuvant Weeks 4, 8, 12, 16, 20, and 24/end of treatment. | Serum prostate-specific antigen (PSA) concentration, expressed in ng/mL, is measured after radical prostatectomy at the adjuvant treatment baseline and at scheduled visits during adjuvant treatment. PSA values are summarized descriptively at each assessment to characterize postoperative PSA dynamics. |
| Pathological Primary Tumor Stage (ypT) After Neoadjuvant Treatment | At final postoperative pathological assessment following radical prostatectomy (surgery planned approximately 26 weeks after treatment initiation). | Pathological primary tumor stage (ypT) is determined by histopathological examination of radical prostatectomy specimens obtained after neoadjuvant treatment. The number and percentage of participants in each ypT category are summarized. |
| Pathological Regional Lymph Node Stage (ypN) After Neoadjuvant Treatment | At final postoperative pathological assessment following radical prostatectomy (surgery planned approximately 26 weeks after treatment initiation). | Pathological regional lymph node stage (ypN) is determined by histopathological examination of pelvic lymph node dissection specimens obtained at radical prostatectomy. The number and percentage of participants in each ypN category are summarized, with unknown or unevaluable nodal status reported separately. |
| Composite Pathological Downstaging Rate (T and/or N) | From pretreatment baseline to final postoperative pathological assessment (surgery planned approximately 26 weeks after treatment initiation). | Percentage of participants with pathological downstaging, assessed by comparing postoperative pathological T and N categories (ypT and ypN) with pretreatment clinical categories (cT and cN). Downstaging requires a lower T category and/or conversion from cN1 to ypN0, with no worsening of either category. Each participant meeting this composite definition is counted once. |
| Positive Surgical Margin Rate | At final postoperative pathological assessment following radical prostatectomy (surgery planned approximately 26 weeks after treatment initiation). | Percentage of participants with a positive surgical margin on final histopathological examination of the radical prostatectomy specimen after neoadjuvant treatment. A positive margin is defined as tumor cells touching the inked resection surface. |
| Objective Response Rate (ORR) at the End of Neoadjuvant Treatment | At the end of neoadjuvant treatment (planned at Week 24), before radical prostatectomy. | Objective response rate is the percentage of participants in the full analysis set with measurable disease at baseline who achieve an overall complete or partial response. Response is assessed by imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at the end of neoadjuvant treatment, before radical prostatectomy. |
| Radical Prostatectomy Rate | During the surgical phase following neoadjuvant treatment (radical prostatectomy planned approximately 26 weeks after treatment initiation). | Percentage of participants in the full analysis set who undergo radical prostatectomy following neoadjuvant study treatment. Surgical status is determined from operative records, and reasons for not undergoing surgery are documented. |
| Rate of Radical Prostatectomy Delay Due to Treatment-Related Adverse Events | From initiation of neoadjuvant treatment through the surgical phase (radical prostatectomy planned approximately 26 weeks after treatment initiation). | Percentage of participants whose planned radical prostatectomy is delayed because of an adverse event assessed by the investigator as related to study treatment. Related events include those considered definitely, probably, or possibly related; delays solely due to reasons unrelated to study treatment are excluded. |
Countries
China
Contacts
CONTACTWen Dong
Outcome results
None listed