A Phase II Neoadjuvant Study of Darolutamide Plus ADT in Men With Localized Prostate Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Darolutamide + ADT Duration of treatment: 28-day cycle of darolutamide treatment and 6 cycles of neoadjuvant therapy. |
Drug: Darolutamide+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
|
Outcome Measures
Primary Outcome Measures
- Rate of pathological downstaging [6 months]
Percentage of patients with tumor downstaging
Secondary Outcome Measures
- pCR or MRD [6 months]
Pathologic complete response or Minimal Residual Disease(defined as overall diameter <5 mm)
- 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
- PSA undetectable rate [12 months post-RP]
PSA<0.02 ng/ml
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male ≥18 years of age.
-
Able to Sign informed consent form independently.
-
Non-metastatic adenocarcinoma of the prostate.
-
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.
-
Subjects with pelvic lymph node involvement(N1) can be included.
-
Candidate for radical prostatectomy with or without pelvic lymph node dissection as per the investigator.
-
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
-
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:
-
Prostate cancer with neuroendocrine differentiation or small cell features
-
Distant metastasis based on conventional imaging (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion.
-
History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer.
-
Subjects who are planning bilateral orchidectomy during the treatment period of the study.
-
Intolerable with darolutamide or ADT treatment.
-
Candidates of other clinical trials.
-
Any prior malignancy within 5 years.
-
Complications include significant cardiovascular disease, active infection, astrointestinal disorders, or any other complications that in the opinion of the investigator.
-
Any condition that in the opinion of the investigator would preclude participation in this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University First Hospital | Beijing | China |
Sponsors and Collaborators
- Peking University First Hospital
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
- Xijing Hospital of Air Force Military Medical University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 22440