Early Salvage Therapy for Patients With Advanced Features for Biochemical Relapse After Radical Prostatectomy for Localized Prostate Carcinoma In Correlation With Supposed Molecular-genetic Parameters of Higher Aggressiveness (ESTABLISH)

August 2, 2022 updated by: Sona Argalacsova, General University Hospital, Prague

The primary objective of the trial is to compare the impact and safety of delayed salvage therapy (dSRT, i.e., SRT initiated at PSA values of 0.4-0.5 ng/ml) to those of early salvage therapy (eSRT, i.e., at PSA levels of 0.2 ng/ml) in patients with biochemical relapse after radical prostatectomy.

The secondary objective of the trial is to perform analysis of the subgroups of patients to determine which patients are most likely to benefit from dSRT

Exploratory objective of the trial is to determine whether selected molecular genetic parameters (172 candidate genes and molecular alterations) and known clinical parameters can be used to identify potential predictors of worse prognosis in patients with known risk factors for relapse after radical prostatectomy, thereby augmenting and refining patient stratification, optimizing their therapy, and clarifying the proper timing of multimodal therapy

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

380

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • > 18 years of age
  • Pathologically confirmed invasive prostate carcinoma with minimal 1 risk factor (RF) after radical prostatectomy (RP)
  • Patient refuses the adjuvant therapy after normalization of urinary function within 6 month after RP
  • Signed informed consent to participate in the study and (where necessary) consent to participate in the translational part of the research (not a requirement)
  • ECOG 0 - 1

  • pT2 and minimal 1 risk factor (RF):

    • R1 (PSM), and/or
    • Gleason score (4+3=7) 8-10 and/or ISUP grade group 3-5
  • pT3a /pT3b with or without one RF
  • No evidence of suspicious pelvic lymph nodes by initial diagnostic: cN0 and/or pN0
  • No evidence of suspicious distant metastases by initial diagnostic: M0
  • Patient with decline of PSA level to undetectable PSA levels (< 0,1 ng/ml) or around 0,2ng/ml and with another decreasing trends so that the PSA level decline within 12-24 weeks after RP to undetectable levels (< 0,1 ng/ml) and with renewed increase of PSA >0,2 ng/ml (BCR= biochemical relapse) without any clinical relapse on PSMA PET/CT
  • No hormonal therapy prior and /or after the radical prostatectomy
  • Patient suitable and fit for subsequent radiotherapy with high likelihood of good compliance to the follow-up

Exclusion Criteria:

  • Life expectancy (based on Charlson comorbidity index) < 10 years
  • Patient not fit for the therapy
  • History of other cancer (other than a radically removed non-melanoma skin carcinoma)
  • Previous pelvic irradiation
  • Active immunosuppressive medication
  • History of hormone therapy prior to randomization
  • cN1 and/or pN1 and M1
  • PSA-persistence after RP (PSA 12-weeks after RP > 0.1 ng/ml or no decreasing trend described in Inclusion criteria)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A- early salvage radiotherapy (eSRT)
Early salvage radiotherapy (eSRT) will be administered immediately after the confirmation of the biochemical relapse (prostate-specific antigen PSA level increase to ≈ 0,2 ng/ml) after radical prostatectomy with defined risk factors and no clinical recurrence signs on prostate specific membrane antigen positron emission tomography and computed tomography (PSMA PET/CT).
Radiation: Early salvage radiotherapy (eSRT)

eSRT administered immediately after the confirmation of the biochemical relapse (PSA ≈ 0.2ng/ml).

66-70Gy will be delivered to the bed of prostate. Radiotherapy will be optionally accompanied by androgen deprivation therapy.
Experimental: Arm B- delayed salvage radiotherapy (dSRT)
The patient is by the biochemical relapse analysis (PSA level 0,2 ng/ml) referred for further follow-up of PSA values. dSRT is initiated, if PSA further increase to values of ≥ 0.4 ng/ml is confirmed and the presence of a potential clinical relapse is excluded with repeated PSMA-PET-CT in line with standard procedures
Radiation: Delayed Salvage radiotherapy (dSRT)

dSRT administered if PSA levels increase to ≥ 0.4 ng/ml.

66-70Gy will be delivered to the bed of prostate. Radiotherapy will be optionally accompanied by androgen deprivation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival (EFS)
Time Frame: Analysed 3 years after randomisation of the last patient.
Defined as a time to re-documented biochemical relapse after salvage therapy (bRFS), demonstration of clinical relapse (i.e.,local relapse /lRFS/, locoregional relapse /lrRFS/, distant relapse /MFS/) and/or death from any cause.
Analysed 3 years after randomisation of the last patient.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Carcinoma-specific survival (CSS)
Time Frame: Analysed 5/10 years after randomization of the last patient.
Analysed 5/10 years after randomization of the last patient.
Overall survival (5y- and 10y- OS)
Time Frame: Analysed 5/10 years after randomization of the last patient.
Analysed 5/10 years after randomization of the last patient.
Incidence of treatment-related acute and late toxicity
Time Frame: Analysed 5 years after randomization of the last patient.

Comparison of the incidence of treatment-related acute and late toxicity between patients after early/ delayed salvage therapy.

Acute and late toxicity will be assessed and graded using Common Terminology Criteria for Adverse Events (CTCAE).
Analysed 5 years after randomization of the last patient.
Health-related quality of life (QoL) assessment.
Time Frame: Analysed 5 years after randomization of the last patient.

The analysis of the QoL of both study ARMs will be made based on EORTC validated questionnaires (QLQ-C30 and QLQ-PR25).

QLQ-C30 was developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. The EORTC QLQ-PR25 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 25 items specifically related to prostate cancer.
Analysed 5 years after randomization of the last patient.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

General University Hospital, Prague

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

September 1, 2022

Primary Completion (Anticipated)

December 1, 2032

Study Completion (Anticipated)

December 1, 2032

Study Registration Dates

First Submitted

November 24, 2021

First Submitted That Met QC Criteria

January 26, 2022

First Posted (Actual)

February 10, 2022

Study Record Updates

Last Update Posted (Actual)

August 3, 2022

Last Update Submitted That Met QC Criteria

August 2, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESTABLISH 2021 Trial v03.2021

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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