Clinical trial NCT05249712: Efficacy and Safety of Darolutamide Combined With ADT in High-risk/Very High-risk Localized Prostate Cancer
Official title: Medical Ethics Committee of Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Zhejiang University
name: The First Affiliated Hospital of Soochow University
First posted: 2022-02-22
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial aims to evaluate the efficacy and safety of neoadjuvant therapy with Darolutamide combined with Androgen-Deprivation Therapy in High-risk/Very high-risk localized prostate cancer. This trial is A prospective, single-arm, multicenter clinical trial. Treatment cycle is 24 weeks,

Detailed description: High risk prostate cancer (PCa) had worse outcomes on radical treatment results, short-time oncological results, even cancer-specific survival, than those low or mediate risk PCa. Neoadjuvant treatment before radical prostatectomy had been proven to get some benefits on peri-operation results, especially on reduction of tumor volume and minimization of biochemical recurrence. This study will evaluate the efficacy and safety of androgen deprivation therapy (ADT) with Darolutamide in neoadjuvant therapy for surgically resectable high-risk or very high-risk PCa.

Eligibility criteria: Inclusion Criteria:

1. Patients must be ≥ 18 and ≤75 years of age；
2. All patients must have a histologically or cytologically diagnosis of prostate cancer，without distant metastasis, and suitable for radical prostatectomy；
3. All patients meet at least one of the following criteria：

   1. multi-parameter MRI or PSMA PET / CT shows clinical staging of primary tumor ≥ T3；
   2. Gleason score of primary tumor ≥ 8；
   3. prostate specific antigen (PSA) ≥20 ng/ml； d) Radiographic assessment of regional lymph node metastases (N1)；
4. Eastern Cooperative Oncology Group (ECOG) physical condition score 0- 1；
5. Patients must have adequate organ function： hematologic function：within 28 days prior to registration as evidenced by: white blood cell (WBC) ≥ 4.0 × 109 / L, platelets≥ 100 × 109 / L, hemoglobin ≥ 9 g / dL and international normalized ratio (INR) \< 1.5； renal function：within 28 days prior to registration, as evidenced by serum creatinine ≤2×ULN； hepatic function: within 28 days prior to registration, as evidenced by: total bilirubin (TBIL)≤1.5 x upper limit of normal (ULN),and SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN；
6. Patients must participate voluntarily and sign an informed consent form (ICF), indicating that they understand the purpose and required procedures of the study, and are willing to participate in. Patients must be willing to obey the prohibitions and restrictions specified in the research protocol.
7. Patients of childbearing potential must be willing to take high-efficiency contraceptive measures during the study period and within 120 days after the last dose of treatment.

Exclusion Criteria:

1. Patients with prostate having neuroendocrine, small cell, or sarcoma-like features are not eligible.
2. Patients with low-risk and medium-risk, localized prostate cancer (the following conditions are met at the same time) are not eligible: multiparameter MRI or PSMA PET / CT shows clinical staging of primary tumor \< T3, Gleason score of primary tumor \< 8, and prostate specific antigen (PSA)。
3. Patients with clinical or radiological evidence of regional or extra-regional lymph node metastases or bone metastases or visceral metastases are not eligible.（any M1）。
4. Patients who have previously received androgen deprivation therapy (medical or surgical) more than 3 months or focal treatment of prostate cancer or prostate cancer radiotherapy or prostate cancer chemotherapy are not eligible
5. Patients with severe or uncontrolled concurrent infections are not eligible。
6. Patients must not have New York Heart Association Class III or IV congestive heart failure at the time of screening. Patients must not have any thromboembolic event, unstable angina pectoris, myocardial infarction within 6 months prior to registration.
7. Patients must not have uncontrolled severe hypertension, persistent uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection.
8. Patients must not have had other malignancies other than prostate cancer in the past 5 years, but cured basal cell or squamous cell skin cancers can be enrolled.
9. The patient is mentally ill, mentally disabled or incapable of giving informed consent

Primary outcomes:
measure: Pathological Response Rate （pCR or MRD）
timeFrame: up to 8months
Secondary outcomes:
measure: AEs/SAEs
timeFrame: Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first
measure: PSA biochemical progression-free survival rate
timeFrame: 3 years
measure: Rate of Positive Surgical Margins
timeFrame: up to 8 months
measure: Rate of Stage Degradation
timeFrame: up to 8 months
measure: PSA response rate
timeFrame: up to 2 years
Other outcomes:
measure: Change From Baseline in Quality of Life as assessed by FACT-P
timeFrame: up to 2 years
measure: Change From Baseline in Quality of life as assessed by BPI-SF
timeFrame: up to 2 years
measure: Change From Baseline in Quality of life as assessed by EPIC-26
timeFrame: up to 2 years
Locations:
city: Nanning
country: China
facility: Hongqian Guo
state: Jiangsu
Study officials:
affiliation: Nanjing Drum Tower Hospital, affiliated to medical school of Nanjing University
name: Hongqian Guo, Phd
role: PRINCIPAL_INVESTIGATOR
References: