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Extended Pelvic Lymph Node Dissection vs. no Pelvic Lymph Node Dissection at Radical Prostatectomy for intermediate-and High-risk Prostate Cancer

Primary Purpose

Prostate Cancer

Status
Terminated
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
Radical prostatectomy (RP) followed by ePLND
Radical prostatectomy (RP) only
Sponsored by
Swiss Group for Clinical Cancer Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Extended pelvic lymph node dissection, Pelvic lymph node dissection, ePLND, Prostate Cancer, intermediate prostate cancer, High-risk prostate cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures.
  • Histologically proven localized adenocarcinoma of the prostate.
  • High-risk prostate cancer or intermediate-risk prostate cancer defined by D'Amico classification system, with an estimated risk of >5% of lymph node metastasis.
  • Patients with a prior malignancy and treated with curative intention are eligible if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence.
  • Age ≥ 18 years and ≤ 80 years.
  • WHO performance status 0-1.
  • Adequate condition (ASA ≤ III) for general anesthesia and radical prostatectomy surgery.
  • Baseline Quality of Life (QoL) questionnaires have been completed.

Exclusion criteria

  • Any pre-operative evidence for T4 disease.
  • Metastatic prostate cancer according to staging or evidence of lymph node metastasis by imaging, defined as any pelvic lymph node >9 mm in the short axis or positive lymph nodes detected by imaging techniques with sensitivities similar or better than PSMA-PET or Choline-PET prior to surgery.
  • PSA ≥ 50 ng/ml.
  • Any prior neo-adjuvant, local or systemic treatment for prostate cancer (alpha reductase inhibitors for treatment of benign hyperplasia are allowed)
  • Previous pelvic lymph node dissection.
  • Any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment.
  • Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Sites / Locations

  • Kantonsspital Aarau AG
  • Universitätsspital Basel
  • Inselspital, Bern
  • Kantonsspital Graubuenden
  • Hôpitaux Universitaires Genève
  • Kantonsspital Baselland
  • Luzerner Kantonsspital
  • Spital Thurgau AG (Frauenfeld and Münsterlingen)
  • Kantonsspital St. Gallen
  • Stadtspital Triemli
  • Universitätsspital Zürich

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

arm A: ePLND

arm B: no PLND

Arm Description

Radical prostatectomy with extended pelvic lymph node dissection

Radical prostatectomy only

Outcomes

Primary Outcome Measures

Time to biochemical recurrence (BCR)
The primary endpoint of this trial is time to BCR, defined as time from randomization to biochemical recurrence, defined as serum PSA level ≥ 0.2 ng/ml, with a second confirmatory serum PSA level ≥ 0.2 ng/ml. Patients not experiencing an event will be censored at the date of the last available assessment or at the start of adjuvant or salvage treatment, if any.

Secondary Outcome Measures

Prostate-specific antigen (PSA) persistence
PSA persistence is defined as failure to reach a PSA value of <0.1 ng/ml within 12 weeks (+ 2 weeks) postoperatively. Patients with no assessments within the first 12 weeks (+ 2 weeks) after surgery will be counted as failures for this endpoint
Time to initiation of adjuvant or salvage therapies
Time to initiation of adjuvant or salvage therapies will be calculated as the time from randomization to the start of any type of adjuvant or salvage therapy. Patients not starting adjuvant or salvage therapies are censored at the last date they were known to be alive.
Time to loco-regional recurrence
Time to loco-regional recurrence will be calculated from randomization until local (prostate bed) or regional (extent of ePLND template) recurrence, whichever occurs first. Patients not experiencing an event will be censored at the date of the last available assessment or at the start of adjuvant or salvage therapy, if any.
Time to distant metastasis
Time to distant metastasis will be calculated from randomization until first occurrence of distant metastasis. Patients not experiencing an event will be censored at the date of the last available assessment.
Prostate cancer-specific survival (PCSS)
PCSS will be calculated as the time from randomization to the date of death due to prostate cancer. Patients who died due to other reasons will be censored at the time of death. All other patients will be censored at the last date they were known to be alive. Causes of death may require critical review by the coordinating investigator and the medical advisor. Particular attention will be paid to men who have been reported as having died from prostate cancer without previously reported progression or recurrence and men who were reported as having died from non-prostate cancer causes after developing biochemical or clinical progression.
Overall survival (OS)
OS will be calculated from randomization until death from any cause. Patients not experiencing an event will be censored at the last date they were known to be alive.
Intraoperative complications
Intraoperative complications will be assessed using the CLASSIC system.
Postoperative complications
Postoperative complications will be assessed using the Clavien-Dindo classification.
Adverse events (AE)
AEs will be assessed according to NCI CTCAE v5.0.

Full Information

First Posted
April 18, 2019
Last Updated
March 7, 2023
Sponsor
Swiss Group for Clinical Cancer Research
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1. Study Identification

Unique Protocol Identification Number
NCT03921996
Brief Title
Extended Pelvic Lymph Node Dissection vs. no Pelvic Lymph Node Dissection at Radical Prostatectomy for intermediate-and High-risk Prostate Cancer
Official Title
Extended Pelvic Lymph Node Dissection vs. no Pelvic Lymph Node Dissection at Radical Prostatectomy for intermediate-and High-risk Prostate Cancer: An International, Multicenter, Randomized Phase III Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Due to lack of funding.
Study Start Date
August 27, 2019 (Actual)
Primary Completion Date
November 11, 2021 (Actual)
Study Completion Date
November 11, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Group for Clinical Cancer Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
For patients with intermediate-risk prostate cancer plus a predicted risk of >5% for positive lymph nodes and with high-risk prostate cancer, international guidelines recommend ePLND along with the RP. Besides an improved accuracy in staging, the therapeutic role of ePLND remains controversial. We hypothesize that ePLND prolongs time to biochemical recurrence (BCR) and prostate cancer-specific survival (PCSS) in intermediate- and high-risk PCa patients.
Detailed Description
Radical prostatectomy (RP) is the surgical standard treatment for men with localized prostate cancer (PCa) and a life expectancy of > 10 years. RP is a treatment option for localized PCa that shows benefit in prostate cancer-specific survival (PCSS) and overall survival compared to conservative management. According to the guideline recommendations of the European Association of Urology (EAU), RP should be accompanied by extended pelvic lymph node dissection (ePLND) in patients with intermediate-risk PCa (D'Amico classification) and > 5% nomogram (Briganti) predicted risk of positive lymph nodes and in all high-risk PCa cases. Besides an improved accuracy in staging, the therapeutic role of ePLND remains controversial. The primary goal of this trial is to provide high-level evidence regarding the therapeutic benefit of ePLND in intermediate- and high-risk PCa patients without clinical evidence of nodal involvement. It is hypothesized that ePLND prolongs time to biochemical recurrence (BCR) and prostate cancer-specific survival (PCSS) in intermediate- and high-risk PCa patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Extended pelvic lymph node dissection, Pelvic lymph node dissection, ePLND, Prostate Cancer, intermediate prostate cancer, High-risk prostate cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
SAKK 09/18 is an international, multicenter, randomized, phase III surgical intervention trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
arm A: ePLND
Arm Type
Experimental
Arm Description
Radical prostatectomy with extended pelvic lymph node dissection
Arm Title
arm B: no PLND
Arm Type
Active Comparator
Arm Description
Radical prostatectomy only
Intervention Type
Procedure
Intervention Name(s)
Radical prostatectomy (RP) followed by ePLND
Intervention Description
ePLND is performed either before or after radical prostatectomy and includes the removal of all nodal and fibro-fatty tissue
Intervention Type
Procedure
Intervention Name(s)
Radical prostatectomy (RP) only
Intervention Description
Radical prostatectomy
Primary Outcome Measure Information:
Title
Time to biochemical recurrence (BCR)
Description
The primary endpoint of this trial is time to BCR, defined as time from randomization to biochemical recurrence, defined as serum PSA level ≥ 0.2 ng/ml, with a second confirmatory serum PSA level ≥ 0.2 ng/ml. Patients not experiencing an event will be censored at the date of the last available assessment or at the start of adjuvant or salvage treatment, if any.
Time Frame
From the date of randomization until the date of biochemical recurrence, assessed up to 15 years after surgery
Secondary Outcome Measure Information:
Title
Prostate-specific antigen (PSA) persistence
Description
PSA persistence is defined as failure to reach a PSA value of <0.1 ng/ml within 12 weeks (+ 2 weeks) postoperatively. Patients with no assessments within the first 12 weeks (+ 2 weeks) after surgery will be counted as failures for this endpoint
Time Frame
From the date of surgery to 14 weeks after surgery
Title
Time to initiation of adjuvant or salvage therapies
Description
Time to initiation of adjuvant or salvage therapies will be calculated as the time from randomization to the start of any type of adjuvant or salvage therapy. Patients not starting adjuvant or salvage therapies are censored at the last date they were known to be alive.
Time Frame
From the date of randomization until the date of start of any type of adjuvant or salvage therapy, assessed up to 15 years after surgery
Title
Time to loco-regional recurrence
Description
Time to loco-regional recurrence will be calculated from randomization until local (prostate bed) or regional (extent of ePLND template) recurrence, whichever occurs first. Patients not experiencing an event will be censored at the date of the last available assessment or at the start of adjuvant or salvage therapy, if any.
Time Frame
From the date of randomization until the date of local or regional recurrence, assessed up to 15 years after surgery
Title
Time to distant metastasis
Description
Time to distant metastasis will be calculated from randomization until first occurrence of distant metastasis. Patients not experiencing an event will be censored at the date of the last available assessment.
Time Frame
From the date of randomization until the date of first occurrence of distant metastasis, assessed up to 15 years after surgery
Title
Prostate cancer-specific survival (PCSS)
Description
PCSS will be calculated as the time from randomization to the date of death due to prostate cancer. Patients who died due to other reasons will be censored at the time of death. All other patients will be censored at the last date they were known to be alive. Causes of death may require critical review by the coordinating investigator and the medical advisor. Particular attention will be paid to men who have been reported as having died from prostate cancer without previously reported progression or recurrence and men who were reported as having died from non-prostate cancer causes after developing biochemical or clinical progression.
Time Frame
From the date of randomization until the date of death due to prostate cancer, assessed up to 15 years after surgery
Title
Overall survival (OS)
Description
OS will be calculated from randomization until death from any cause. Patients not experiencing an event will be censored at the last date they were known to be alive.
Time Frame
From the date of randomization until the date of death, assessed up to 15 years after surgery
Title
Intraoperative complications
Description
Intraoperative complications will be assessed using the CLASSIC system.
Time Frame
During surgery
Title
Postoperative complications
Description
Postoperative complications will be assessed using the Clavien-Dindo classification.
Time Frame
From the date of surgery to 14 weeks after surgery
Title
Adverse events (AE)
Description
AEs will be assessed according to NCI CTCAE v5.0.
Time Frame
From the date of registration to 15 years after surgery

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures. Histologically proven localized adenocarcinoma of the prostate. High-risk prostate cancer or intermediate-risk prostate cancer defined by D'Amico classification system, with an estimated risk of >5% of lymph node metastasis. Patients with a prior malignancy and treated with curative intention are eligible if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence. Age ≥ 18 years and ≤ 80 years. WHO performance status 0-1. Adequate condition (ASA ≤ III) for general anesthesia and radical prostatectomy surgery. Baseline Quality of Life (QoL) questionnaires have been completed. Exclusion criteria Any pre-operative evidence for T4 disease. Metastatic prostate cancer according to staging or evidence of lymph node metastasis by imaging, defined as any pelvic lymph node >9 mm in the short axis or positive lymph nodes detected by imaging techniques with sensitivities similar or better than PSMA-PET or Choline-PET prior to surgery. PSA ≥ 50 ng/ml. Any prior neo-adjuvant, local or systemic treatment for prostate cancer (alpha reductase inhibitors for treatment of benign hyperplasia are allowed) Previous pelvic lymph node dissection. Any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment. Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cyrill A. Rentsch, MD-PhD
Organizational Affiliation
University Hospital Basel, Department of Urology
Official's Role
Study Chair
Facility Information:
Facility Name
Kantonsspital Aarau AG
City
Aarau
ZIP/Postal Code
5001
Country
Switzerland
Facility Name
Universitätsspital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Name
Inselspital, Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Kantonsspital Graubuenden
City
Chur
ZIP/Postal Code
7000
Country
Switzerland
Facility Name
Hôpitaux Universitaires Genève
City
Genève
ZIP/Postal Code
1211
Country
Switzerland
Facility Name
Kantonsspital Baselland
City
Liestal
ZIP/Postal Code
4410
Country
Switzerland
Facility Name
Luzerner Kantonsspital
City
Luzern
ZIP/Postal Code
6000
Country
Switzerland
Facility Name
Spital Thurgau AG (Frauenfeld and Münsterlingen)
City
Münsterlingen
ZIP/Postal Code
8596
Country
Switzerland
Facility Name
Kantonsspital St. Gallen
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Stadtspital Triemli
City
Zürich
ZIP/Postal Code
8063
Country
Switzerland
Facility Name
Universitätsspital Zürich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Learn more about this trial

Extended Pelvic Lymph Node Dissection vs. no Pelvic Lymph Node Dissection at Radical Prostatectomy for intermediate-and High-risk Prostate Cancer

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