Genomic Biomarker-guided Neoadjuvant Therapy for Prostate Cancer (SEGNO) (SEGNO)

An Exploratory Study of the Safety and Efficacy of Genomic Biomarker-guided Neoadjuvant Therapy for Locally Advanced and Oligometastatic Prostate Cancer (SEGNO)

To evaluated the safety and efficacy of genomic biomarker-guided neoadjuvant therapy for locally advanced and oligometastatic prostate cancer.

Study Overview

• Status: Recruiting
• Conditions: Oligometastatic Prostate Cancer; Locally Advanced Prostate Cancer
• Intervention / Treatment: Drug: Rezvilutamide; Drug: Goserelin Microspheres for Injection; Drug: Docetaxel; Drug: Pamiparib; Drug: Cisplatin; Drug: Tislelizumab

Detailed Description

According to the results of the genomic profile, patients will be assigned to 4 neoadjuvant therapy (NT) groups (Queue 1 to 4): Queue 1: No targetable actionable aberration; Queue 2: Homologous recombination repair (HRR) alterations (BRCA1/2); Queue 3: Homologous recombination repair alterations (except BRCA1/2 and CDK12); Queue 4: MSI-H/dMMR, TMB≥10mut/Mb or CDK12 alterations without other HRR alterations. A following PSMA PETCT for evaluating the efficacy of NT and radical prostatectomy (RP) plus pelvic lymph node dissection (PLND) will be perform. The histopathological and survival data after RP plus PLND will also be evaluated.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kaiyan Zhang, M.D.; Phone Number: +865922139714; Email: zkyken@163.com
• Study Contact Backup: Name: Haichao Huang, M.D.; Phone Number: +865922139493; Email: hhc_pku@163.com

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361000
      • Recruiting
      • The first affiliated hospital of xiamen university
      • Contact: Kaiyan Zhang, M.D.; Phone Number: +865922139714; Email: zkyken@163.com
      • Contact: Haichao Huang, M.D.; Phone Number: +865922139493; Email: hhc_pku@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males ≥ 18 years of age;
• Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrolment in the trial to document their willingness to participate;
• Imaging examination (defined by multiparametric magnetic resonance imaging, radionuclide bone scan and PSMA PET/CT (prostate-specific membrane antigen positron emission tomography/computed tomography) confirmed locally advanced (identified as cT3b to cT4, N0 to N1, M0) and oligometastatic (identified as no visceral metastasis and ≤5 bone metastases) prostate cancer. Participants are considered tolerable to radical prostatectomy (RP) and pelvic lymph node dissection (PLND) after neoadjuvant therapy (NT). Participants must consent to RP and PLND after NT when defined as tolerable for RP and PLND at registration and prior to enrolment in the trial;
• Histologically confirmed adenocarcinoma of the prostate without pathologic evidence of small cell and neuroendocrine differentiation at the time of initial diagnosis;
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and a life expectancy of ≥ 3 years;
• Participants must have adequate end-organ function to tolerate NT and subsequent RP+PLND and all laboratory tests must be performed within 4 weeks prior to registration into master protocol. Including the following indicators: hemoglobin (Hb) ≥85g/L; White blood cell count (WBC) ≥3.0×109 /L; Platelet (PLT) ≥ 75×109 /L; Liver function: Total bilirubin (TBIL) ≤1.5×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5× upper limit of normal value (ULN); Albumin (ALB) ≥25g/L; Renal function: glomerular filtration rate (GFR) ≥ 60ml/min;
• Participants must consent to genetic testing at registration and prior to enrolment in the trial;
• No prior systemic or localized treatment for prostate cancer. Up to 28 days of LHRHa, non-steroidal anti-androgen (NSAA) and novel hormone therapy (rezvilutamide) are allowable prior to treatment;
• Participants must have the ability to swallow oral medication and follow the study procedure;
• Participants must consent to use reliable contraceptive methods (such as condoms) and not to donate sperm throughout the study period and for 3 months after the last NT administration;
• Participants must have no contraindications to any of the relevant drug treatments in the study.

Exclusion Criteria:

• Participants with a history of hypersensitivity to any of the relevant drugs involved in this study;
• Participants received more than 28 days of LHRHa, non-steroidal anti-androgen (NSAA) and novel hormone therapy (rezvilutamide) prior to registration, or enrolled in any other clinical studies for therapeutic purposes within 28 days prior to enrollment, or received any approved anticancer therapy within 28 days prior to enrollment;
• Participants received local treatments of primary or metastatic lesions prior to enrollment;
• Participants received bilateral orchiectomy prior to enrollment;
• Hypogonadism or severe androgen deficiency as defined by screening serum testosterone more than 50 ng/dL below the normal range for the institution;
• Participants with a history of brain metastases or epilepsy;
• Participants with severe cardiovascular disease, including: myocardial infarction or thrombosis in the previous 6 months; known unstable angina; history of documented congestive heart failure (New York Heart Association functional classification III-IV; QT interval > 480 ms; uncontrolled hypertension defined as resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg;
• Participants with clinically significant digestive tract abnormalities that may affect the process of drug intake, transport, or absorption (e.g. inability to swallow, chronic diarrhea, intestinal obstruction, etc., or total gastrectomy);
• Participants with other clinically significant co-morbidities evaluated by the investigator, including uncontrolled lung disease, active central nervous system disease, active or uncontrolled bacterial, viral, or fungal infections requiring systemic treatment, or any other disease that may make the participant inappropriate for enrollment or RT + PLND after NT;
• Participants with other known active cancers requiring treatment at the time of entry to the study, or had other malignancies within 5 years prior to enrollment;
• Participants received surgeries other than diagnostic prostate biopsy within 4 weeks before enrollment;
• Participants with active or known human immunodeficiency virus (HIV) with detectable viral load; active hepatitis B, defined as positive HBV DNA viral load or as defined by relevant guidelines; hepatitis C virus (HCV), except for those have been treated and have an undetectable viral load;
• Participants with a history of non-compliance to medical regimen or inappropriate for the study, attributed to not meeting the principle of optimal benefit treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Queue 1; Rezvilutamide plus ADT plus docetaxel.	Drug: Rezvilutamide; 240mg by mouth once a day for 24 weeks.; Drug: Goserelin Microspheres for Injection; 3.6mg by intramuscular injection once 4 weeks for 24 weeks.; Drug: Docetaxel; 70mg/m2 by infusion every 3 weeks for 6 cycles (each cycle has 3 weeks).
Experimental: Queue 2; Rezvilutamide plus ADT plus pamiparib.	Drug: Rezvilutamide; 240mg by mouth once a day for 24 weeks.; Drug: Goserelin Microspheres for Injection; 3.6mg by intramuscular injection once 4 weeks for 24 weeks.; Drug: Pamiparib; 60mg by mouth twice a day for 20 weeks.
Experimental: Queue 3; Rezvilutamide plus ADT plus cisplatin.	Drug: Rezvilutamide; 240mg by mouth once a day for 24 weeks.; Drug: Goserelin Microspheres for Injection; 3.6mg by intramuscular injection once 4 weeks for 24 weeks.; Drug: Cisplatin; 70mg/m2 by infusion every 3 weeks for 6 cycles (each cycle has 3 weeks).
Experimental: Queue 4; Rezvilutamide plus ADT plus tislelizumab.	Drug: Rezvilutamide; 240mg by mouth once a day for 24 weeks.; Drug: Goserelin Microspheres for Injection; 3.6mg by intramuscular injection once 4 weeks for 24 weeks.; Drug: Tislelizumab; 200 mg by infusion every 3 weeks for 6 cycles (each cycle has 3 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of clinical complete response (cCR)	The rate of clinical complete response (cCR) as assessed using PSMA PET/CT and mp-MRI following 20 weeks of neoadjuvant therapy	20 weeks
Rate of pathological minimal residual disease (pMRD)	The rate of pathological minimal residual disease (defined as residual tumour 5 mm or less) as assessed on prostatectomy specimens following 24 weeks of neoadjuvant therapy	24 weeks
Rate of complete pathologic response (pCR)	The rate of complete pathologic response (pCR) as assessed on prostatectomy specimens following 24 weeks of neoadjuvant therapy	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Kaplan-Meier curves	3 years
Overall survival	Kaplan-Meier curves	3 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xiamen University
• Investigators: Principal Investigator: Kaiyan Zhang, M.D., The first affiliated hospital of xiamen university

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: April 21, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Poly(ADP-ribose) Polymerase Inhibitors; Docetaxel; Goserelin; Tislelizumab; Pamiparib
• Other Study ID Numbers: XMYY-2024KY040

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