Prostate Cancer
Conditions
Brief summary
Scientific Rationale: High risk localized prostate cancer (PCa) is associated with higher rates of biochemical recurrence, clinical recurrence, metastasis and PCa-specific death. Novel hormone therapies(NHT) have shown a significant survival advantage with respect to classical ADT in later stages of PCa and have already been investigated in neoadjuvant setting. PURPOSE: To assess antitumor effect by measuring pathological tumor volume with pathological downstaging following radical prostatectomy + pelvic lymph-node dissection (RP + PLND) for high-risk localized prostate cancer patients.
Interventions
DRUGDarolutamide+ADT
Drug: Darolutamide Darolutamide 600 mg, (two 300 mg tablets) administered orally twice daily. Swallow tablets whole. Take Darolutamide with food. Drug: ADT GnRH agonist per physicians' choice, orchiectomy is excluded
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
The First Affiliated Hospital of Air Force Medicial University
Peking University First Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male ≥18 years of age. 2. Able to Sign informed consent form independently. 3. Non-metastatic adenocarcinoma of the prostate. 4. Subjects must have as least one of the following features according to NCCN definition of high-risk: Gleason score ≥8, or PSA \>20ng/ml,or≥clinical T3a. 5. Subjects with pelvic lymph node involvement(N1) can be included. 6. Candidate for radical prostatectomy with or without pelvic lymph node dissection as per the investigator. 7. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. 8. Subjects must have normal organ and marrow function as defined below: Hemoglobin ≥ 9.0 g/dL;Absolute neutrophil count (ANC) ≥ 1,500/mcL; Platelets ≥ 100,000/mcL, independent of transfusions/growth factors within 3 months of treatment start; Serum potassium ≥ 3.5 mmol/L; Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN) (except in subjects with Gilbert's syndrome who have a total bilirubin \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible);Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN;Serum albumin ≥ 3.0 g/dL;Serum creatinine \< 2.0 x ULN.
Exclusion criteria
1. Prostate cancer with neuroendocrine differentiation or small cell features 2. Distant metastasis based on conventional imaging (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. 3. History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer. 4. Subjects who are planning bilateral orchidectomy during the treatment period of the study. 5. Intolerable with darolutamide or ADT treatment. 6. Candidates of other clinical trials. 7. Any prior malignancy within 5 years. 8. Complications include significant cardiovascular disease, active infection, astrointestinal disorders, or any other complications that in the opinion of the investigator. 9. Any condition that in the opinion of the investigator would preclude participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of pathological downstaging | 6 months | Percentage of patients with tumor downstaging |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSM | 6 months | Percentage of patients with positive surgical margins |
| Rate of peri-operative complications | within 30 days of surgery | including delay in surgery, intra-operative complications, and postoperative complications |
| Biochemical complete response | 6 months | PSA \<0.1ng/ml prior to RP |
| pCR or MRD | 6 months | Pathologic complete response or Minimal Residual Disease(defined as overall diameter \<5 mm) |
| 2-year biochemical progression-free survival, bPFS | 24 months post-RP | PSA\>0.2 ng/ml |
| AEs/SAEs | Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first | The level of AEs defined by NCI-CTCAE v5.0. Safety assessments will be assessed and documented after initiation of study drug, regardless of relationship to study drug. |
| PSA undetectable rate | 12 months post-RP | PSA\<0.02 ng/ml |
Countries
China
Contacts
Primary ContactZhisong He, MD
Backup ContactKaiwei Yang, MD
Outcome results
None listed