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

April 11, 2023 updated by: Martini-Klinik am UKE GmbH

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

452

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • Germany
    • Nein
      • Hamburg, Nein, Germany, 20246
        • Markus Graefen

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 to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

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
Other: Radical prostatectomy and BST
BST plus radical prostatectomy with ext. lymphadenectomy
Procedure: Radical prostatectomy
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.
Other: Best Systemic Therapy (BST)
e.g. Androgen deprivation therapy, chemotherapy, others
Drug: Best systemic therapy

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.

Other Names:
  • Androgen deprivation therapy, chemotherapy, others

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cancer specific survival
Time Frame: 10 years
Follow-up visits every 3 months
10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Developement of castration-resistance measured by PSA value
Time Frame: 10 years
Follow-up visits every 3 months
10 years
Overall survival
Time Frame: 10 years
Follow-up visits every 3 months
10 years
Progression-free survival
Time Frame: 10 years
Follow-up visits every 3 months
10 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of Life measured by the EPIC-26
Time Frame: 10 years
Using a questionnaire, Follow-up visits every 3 months
10 years

Collaborators and Investigators

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

Sponsor

Martini-Klinik am UKE GmbH

Collaborators

Förderverein Hilfe bei Prostatakrebs e.V.

Investigators

  • Principal Investigator: Markus Graefen, Professor, Martini-Klinik am UKE GmbH

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

May 1, 2015

Primary Completion (Actual)

December 1, 2019

Study Completion (Anticipated)

December 31, 2026

Study Registration Dates

First Submitted

May 8, 2015

First Submitted That Met QC Criteria

May 22, 2015

First Posted (Estimate)

May 27, 2015

Study Record Updates

Last Update Posted (Actual)

April 12, 2023

Last Update Submitted That Met QC Criteria

April 11, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • G-RAMPP_MK-2014
  • AP 75/13 (Other Identifier: Arbeitsgemeinschaft urologische Onkologie)

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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