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Impact of Radical Prostatectomy as Primary Treatment in Patients With Prostate Cancer With Limited Bone Metastases (g-RAMPP)

Primary Purpose

Prostate Cancer

Status
Active
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Radical prostatectomy
Best systemic therapy
Sponsored by
Martini-Klinik am UKE GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring metastatic, prostatectomy, androgen deprivation, best systemic therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Patients with locally resectable intermediate and high-risk prostate cancer which has been confirmed by biopsy according to D'Amico criteria (intermediate risk: PSA 10-20 ng/ml, cT2b-c, Gleason score 7; high risk: PSA >20 ng/ml, >cT2c, Gleason score 8-10) with clinical evidence of bone metastases in imaging tests can be included. Necessary radiotherapy of the bone metastases as required is also permitted prior to inclusion in the study.

In line with the results from the recent CHAARTED and STAMPEDE studies (Sweeny et al., 2015, James et al 2015), early treatment with taxanes may be used in both the standard treatment arm as well as in the intervention arm where the prostatektomie is performed. The period 6 months from the initial diagnosis to randomization and possibly three months from randomization to surgery must be complied with.

Inclusion criteria

  1. Patients with newly diagnosed prostate cancer which has been confirmed by histological examination (within the last 6 months prior to randomization)
  2. At least one and at most 5 bone metastases in imaging tests (bone scintigraphy, CT, MRT or PET) at diagnosis with no evidence of visceral metastasis. Patients with evidence of lymph node metastasis (N1) are allowed
  3. PSA ≤ 200 ng/ml at diagnosis (without ADT)
  4. Asymptomatic or mild symptomatic disease
  5. Locally resectable tumour stage
  6. ECOG Performance Score 0-1
  7. Submission of the patient's written declaration of informed consent following explanation
  8. Age ≥ 18 - ≤ 75 years
  9. Full legal capacity and compliance of the Patient

Exclusion Criteria:

  • Contraindications to radical prostatectomy (Local non-resectable disease, increased anesthetic risk due to comorbidities)
  • Detection of more than 5 bone metastases
  • Pain management with opioid analgetics
  • Evidence of visceral metastases or brain metastases
  • Neuroendocrine and / or small cell differentiation in histology of the biopsy
  • Charlson Comorbidity Index > 2
  • ECOG Performance Score > 1
  • Myocardial infarction or stroke within the last 6 months
  • Existing major cardiovascular (grade III - IV according to NYHA), pulmonary (pO2 <60 mmHg), renal, hepatic or hematopoietic disease (e.g. severe bone marrow aplasia)
  • Severe psychiatric disorders persons housed on judicial or administrative arrangement in an institution
  • Simultaneous participation in another clinical trial with interventional character of the metastatic prostate cancer

Sites / Locations

  • Markus Graefen

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Radical prostatectomy and BST

Best Systemic Therapy (BST)

Arm Description

BST plus radical prostatectomy with ext. lymphadenectomy

e.g. Androgen deprivation therapy, chemotherapy, others

Outcomes

Primary Outcome Measures

Cancer specific survival
Follow-up visits every 3 months

Secondary Outcome Measures

Developement of castration-resistance measured by PSA value
Follow-up visits every 3 months
Overall survival
Follow-up visits every 3 months
Progression-free survival
Follow-up visits every 3 months

Full Information

First Posted
May 8, 2015
Last Updated
April 11, 2023
Sponsor
Martini-Klinik am UKE GmbH
Collaborators
Förderverein Hilfe bei Prostatakrebs e.V.
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1. Study Identification

Unique Protocol Identification Number
NCT02454543
Brief Title
Impact of Radical Prostatectomy as Primary Treatment in Patients With Prostate Cancer With Limited Bone Metastases
Acronym
g-RAMPP
Official Title
Multicentric, Prospective, Randomized Controlled Trial Comparing Best Systemic Therapy (BST) With Radical Prostatectomy or BST Alone in the Management of Men With Pauci-metastatic Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 2015 (undefined)
Primary Completion Date
December 2019 (Actual)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Martini-Klinik am UKE GmbH
Collaborators
Förderverein Hilfe bei Prostatakrebs e.V.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of the study is to investigate, the effect of radical prostatectomy with extended lymphadenectomy on cancer-specific survival, time to castration-resistance, time to progression and quality of life in patients with a limited bone metastatic prostate cancer. In addition the influence of patient- and disease-related factors on clinical outcome (prognostic effect) and on the comparison therapy (predictive effect) will be examined. Amendment05: Due to the slow tumor biology of prostate cancer, the follow-up period of 5 years is not sufficient to reach the primary endpoint of the study. For this reason, the follow-up is extended for a further 5 years with 2 visits per year.
Detailed Description
More recent data has shown that performing local therapy with lymphogenic metastatic prostate cancer has resulted in a definite benefit in cancerspecific and overall survival. The analysis of this data has led to a change of paradigm in the treatment of lymphogenic metastatic prostate cancer (Isbarn Deutsches Ärzteblatt 2013). Patients with low lymphogenic metastatic load and low comorbidity are therefore frequently given local therapy. In a retrospective review of patients with lymphogenic metastatic prostate cancer, who were either treated by means of best systemic therapy or best systemic therapy plus radical prostatectomy, a highly significant benefit is shown for the patient group which received surgery (Engel et al., Eur Urol 2012). The 5 and 10 year overall survival rate in this cohort was 84% and 64% respectively following RP and in the other cohort with best systemic therapy without RP 60% and 28% respectively. Our own working group was able to confirm this clear survival benefit in the lymphogenic metastatic stage for patients who received surgery: in a matched pair analysis the clinically progression-free survival rate after 5 and 10 years was 77% and 61% respectively after additional RP and 61% and 31% respectively with best systemic therapy alone (p=0.005). The same trend was found for cancer-specific survival (84% and 76% with additional RP versus 81% and 46% with best systemic therapy alone (p=0.001) (Steuber et al., BJUI 2011). The impressive improvements in the survival rates of lymphogenic metastatic prostate cancer through local therapy compared with best systemic therapy alone suggests that patients with distant metastases could potentially also benefit from local therapy. Besides possible effects on tumour control, the RP could also be beneficial with regard to a local progression of the prostate cancer (rectal infiltration, infiltration of the bladder). This could lead to an improvement in the quality of life in the course of the disease. On the other hand, radical prostatectomy is associated with potential side-effects (e.g. urinary incontinence in approximately 5 - 10% of patients as well as possible general side-effects, such as thrombosis, embolism, impaired wound healing etc.), which can lead to a loss in terms of quality of life.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
metastatic, prostatectomy, androgen deprivation, best systemic therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
452 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Radical prostatectomy and BST
Arm Type
Other
Arm Description
BST plus radical prostatectomy with ext. lymphadenectomy
Arm Title
Best Systemic Therapy (BST)
Arm Type
Other
Arm Description
e.g. Androgen deprivation therapy, chemotherapy, others
Intervention Type
Procedure
Intervention Name(s)
Radical prostatectomy
Intervention Description
Study participants randomized in the intervention arm receive best systemic therapy in addition to radical prostatectomy with extended lymphadenectomy. It is not crucial whether the radical prostatectomy is performed open or robot-assisted.
Intervention Type
Drug
Intervention Name(s)
Best systemic therapy
Other Intervention Name(s)
Androgen deprivation therapy, chemotherapy, others
Intervention Description
For the antiandrogenic therapy a non-steroidal antiandrogen (e.g. flutamide, bicalutamide) or a gonadotropin-releasing hormone (GnRH) analogues (e.g. goserelin, leuprolide) are available. The selection of best systemic therapy is up to the judgment of the treating urologist.
Primary Outcome Measure Information:
Title
Cancer specific survival
Description
Follow-up visits every 3 months
Time Frame
10 years
Secondary Outcome Measure Information:
Title
Developement of castration-resistance measured by PSA value
Description
Follow-up visits every 3 months
Time Frame
10 years
Title
Overall survival
Description
Follow-up visits every 3 months
Time Frame
10 years
Title
Progression-free survival
Description
Follow-up visits every 3 months
Time Frame
10 years
Other Pre-specified Outcome Measures:
Title
Quality of Life measured by the EPIC-26
Description
Using a questionnaire, Follow-up visits every 3 months
Time Frame
10 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Patients with locally resectable intermediate and high-risk prostate cancer which has been confirmed by biopsy according to D'Amico criteria (intermediate risk: PSA 10-20 ng/ml, cT2b-c, Gleason score 7; high risk: PSA >20 ng/ml, >cT2c, Gleason score 8-10) with clinical evidence of bone metastases in imaging tests can be included. Necessary radiotherapy of the bone metastases as required is also permitted prior to inclusion in the study. In line with the results from the recent CHAARTED and STAMPEDE studies (Sweeny et al., 2015, James et al 2015), early treatment with taxanes may be used in both the standard treatment arm as well as in the intervention arm where the prostatektomie is performed. The period 6 months from the initial diagnosis to randomization and possibly three months from randomization to surgery must be complied with. Inclusion criteria Patients with newly diagnosed prostate cancer which has been confirmed by histological examination (within the last 6 months prior to randomization) At least one and at most 5 bone metastases in imaging tests (bone scintigraphy, CT, MRT or PET) at diagnosis with no evidence of visceral metastasis. Patients with evidence of lymph node metastasis (N1) are allowed PSA ≤ 200 ng/ml at diagnosis (without ADT) Asymptomatic or mild symptomatic disease Locally resectable tumour stage ECOG Performance Score 0-1 Submission of the patient's written declaration of informed consent following explanation Age ≥ 18 - ≤ 75 years Full legal capacity and compliance of the Patient Exclusion Criteria: Contraindications to radical prostatectomy (Local non-resectable disease, increased anesthetic risk due to comorbidities) Detection of more than 5 bone metastases Pain management with opioid analgetics Evidence of visceral metastases or brain metastases Neuroendocrine and / or small cell differentiation in histology of the biopsy Charlson Comorbidity Index > 2 ECOG Performance Score > 1 Myocardial infarction or stroke within the last 6 months Existing major cardiovascular (grade III - IV according to NYHA), pulmonary (pO2 <60 mmHg), renal, hepatic or hematopoietic disease (e.g. severe bone marrow aplasia) Severe psychiatric disorders persons housed on judicial or administrative arrangement in an institution Simultaneous participation in another clinical trial with interventional character of the metastatic prostate cancer
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Markus Graefen, Professor
Organizational Affiliation
Martini-Klinik am UKE GmbH
Official's Role
Principal Investigator
Facility Information:
Facility Name
Markus Graefen
City
Hamburg
State/Province
Nein
ZIP/Postal Code
20246
Country
Germany

12. IPD Sharing Statement

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Impact of Radical Prostatectomy as Primary Treatment in Patients With Prostate Cancer With Limited Bone Metastases

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