Salvage Radiotherapy Combined With Androgen Deprivation Therapy (ADT) With or Without Rezvilutamide in the Treatment of Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer

Salvage Radiotherapy Combined With Androgen Deprivation Therapy (ADT) With or Without Rezvilutamide in the Treatment of Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer: a Prospective, Multicenter, Randomized Controlled Clinical Study

To evaluate the efficacy and safety of rezvilutamide in combination with androgen deprivation therapy(ADT) and standard salvage radiation therapy(SRT) or SRT combination with ADT in prostate cancer patients with biochemical recurrence of prostate-specific antigen(PSA) persistence after radical prostatectomy(RP).

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Biochemical Recurrence
• Intervention / Treatment: Drug: Rezvilutamide; Radiation: SRT; Drug: Androgen deprivation therapy (ADT)

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shun Zhang, MD; Phone Number: 15050589789; Email: explorershun@126.com
• Study Contact Backup: Name: Hongqian Guo, Phd; Phone Number: 13605171690; Email: dr.ghq@nju.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University
      • Contact: Shun Zhang; Phone Number: 15050589789 15050589789; Email: explorershun@126.com
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
      • Contact: Hongqian Guo, Phd; Phone Number: 13605171690; Email: dr.ghq@nju.edu.cn
      • Contact: Shun Zhang
      • Principal Investigator: Hongqian Guo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. ≥40 years old, male;
• 2. Postoperative pathology showed prostate adenocarcinoma;
• 3. Postoperative pathological stage pN0 or pNx;
• 4. PSA decline < 0.1ng/ml within 8 weeks after radical prostate cancer surgery for at least 6 months
• 5. Biochemical recurrence (PSA rose twice in a row, with an interval of ≥2 weeks and absolute value > 0.2ng/ml), and traditional imaging (bone scan and CT/MRI scan) did not show local recurrence and distant metastasis.

• 6. Have one or more of the following risk factors:

  • Postoperative CAPRA-S score ≥6 points;
  • The pathological score of radical surgery for prostate cancer was Gleason 8-10;
  • The highest postoperative biochemical recurrence PSA > 0.5ng/ml;
  • Postoperative pathological stage PT3/T4;
  • PSADT < 10 months;
• 7. ECOG status is 0-1;
• 8. Life expectancy greater than 10 years;

• 9. Adequate hematological and organ function tests within 4 weeks prior to the first study treatment, as defined below:

  • Neutrophil count (ANC)≥1.5×10^9/L (no granulocyte colony-stimulating factor for 2 weeks prior to cycle 1, day 1);
  • Platelet count (PLT)≥100×10^9/L (no transfusion within 2 weeks prior to day 1 of cycle 1);
  • Hemoglobin (Hb) ≥90g/L
  • Serum creatinine (Cr)≤1.5×ULN or creatinine clearance > 50ml/min;
  • Total bilirubin (BIL)≤1.5×ULN;
  • Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) level ≤2.5×ULN;
  • International Standardized ratio (INR) ≤1.5, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN;
  • Left ventricular ejection fraction (LVEF) ≥50%;
• 10. The subject is willing and understands to sign the informed consent and is able to comply with the agreement.

Exclusion Criteria:

• 1. Previously received endocrine therapy for prostate cancer (including but not limited to goserrelin, levoprorelin, digarek, bicalutamide, abiraterone acetate, darotamine, apatamide, enzalutamide, etc.) or pelvic radiotherapy;
• 2. Postoperative biochemical recurrence, but PSA more than 2 ng/ml;
• 3. Postoperative pathology contains non-adenocarcinoma components, such as neuroendocrine differentiation or small cell features;
• 4. Is currently participating in or has participated in an investigational drug study;
• 5. Known or suspected allergy to reverumide and reverumide excipients;
• 6. Inability to swallow, chronic diarrhea, intestinal obstruction, or other factors that affect drug use and absorption;
• 7. Have a history of epilepsy, or a medical condition that can induce seizures within the 12 months prior to C1D1 (including a history of transient ischemic attacks, cerebral stroke, traumatic brain injury with disturbance of consciousness requiring hospitalization);
• 8. Active heart disease in the 6 months prior to C1D1, including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, and medically treatable ventricular arrhythmias;
• 9. Have had any other malignancies within the 3 years prior to C1D1 (except for carcinoma in situ that has been in complete remission and malignancies that the investigator determined to be slowly progressing);
• 10. Granulocyte colony-stimulating factor was used for support 2 weeks before C1D1;
• 11. Blood transfusion within 2 weeks before C1D1;
• 12. Active HBV and HCV infected persons (HBV copy number ≥10^4 copies /mL, HCV copy number ≥10^3 copies /mL);
• 13. A history of immunodeficiency (including HIV positive, other acquired, congenital immunodeficiency diseases) or a history of organ transplantation;
• 14. Male subjects whose partner is a fertile woman refuse surgical sterilization or use of effective contraception during the trial period and for 3 months after the last dose of riverutamide.
• 15. The investigator determines subjects who may affect the conduct of clinical studies, who may not be able to comply with the protocol or cooperate with the protocol, and who pose research risks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rezvilutamide +ADT+ SRT; Rezvilutamide along with ADT for 6 cycles (28 days for each cycle) in combination with salvage radiation therapy (SRT) according to standard of care	Drug: Rezvilutamide; Specifications of 80 mg; orally, once a day; Other Names: SHR3680; Radiation: SRT; SRT according to standard of care (66.6-72 grays will be delivered to the bed of prostate ,~50.4 grays to the pelvis if needed); Drug: Androgen deprivation therapy (ADT); Androgen deprivation therapy (ADT), the ADT used by each subject will be determined by the investigator,and the dose and frequency of administration will be consistent with the prescription information
Other: ADT+ SRT; ADT for 6 cycles (28 days for each cycle) in combination with salvage radiation therapy (SRT) according to standard of care	Radiation: SRT; SRT according to standard of care (66.6-72 grays will be delivered to the bed of prostate ,~50.4 grays to the pelvis if needed); Drug: Androgen deprivation therapy (ADT); Androgen deprivation therapy (ADT), the ADT used by each subject will be determined by the investigator,and the dose and frequency of administration will be consistent with the prescription information

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year biochemical progression-free survival	biochemical progression is defined as a confirmed prostate specific antigen (PSA) greater than (>) 0.2 nanogram per milliliter (ng/ml) ( the time interval should be over 2 weeks)	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival (PFS)	Time from entry to biochemical progression or radiologically confirmed progressive disease or death due to any cause	48 months
metastasis-free survival (MFS)	Time from entry to radiologically confirmed metastasis disease or death due to any cause.	48 months
percentage of undetectable PSA	percentage of undetectable PSA is defined as the proportion of subjects with a PSA level ≤ 0.1 ng/mL after enrollment	48 months
ctDNA-positive rate	ctDNA-positive rate was defined as the number of ctDNA subjects detected in the total enrolled population	48 months
ctDNA clearance rate	Defined as the number of patients who were ctDNA-positive at enrollment to ctDNA-negative after treatment as a proportion of ctDNA-positive patients enrolled	48 months
Adverse Events	According to NCI-CTCAE v5.0	48 months

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: March 5, 2024
• First Submitted That Met QC Criteria: March 5, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Prostate cancer; Biochemical recurrence; Rezvilutamide
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Disease Attributes; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Recurrence; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens
• Other Study ID Numbers: IUNU-PC-120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No