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Trial of Ultrahypofractionated Focal Salvage Radiotherapy for Isolated Prostate Bed Recurrence After Radical Prostatectomy (HypoFocal SRT)

Primary Purpose

Recurrent Prostate Cancer

Status
Recruiting
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Ultrahypofractionated salvage radiotherapy to a local recurrence after radical prostatectomy
Androgen deprivation therapy
Sponsored by
Insel Gruppe AG, University Hospital Bern
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Prostate Cancer focused on measuring Prostate, Salvage Radiation, Local recurrence, Stereotactic radiotherapy, Hypofractionation

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: Written informed consent according to ICH/GCP (International Council for Harmonisation/Good Clinical Practice) regulations before registration and prior to any trial specific procedures Age ≥ 18 years at time of registration WHO performance status 0-1 Lymph node negative adenocarcinoma of the prostate treated with radical prostatectomy (RP) at least 6 months before trial Tumor stage pT2a-3b, R0-1, pN0 or cN0 according to the Union for International Cancer Control (UICC) TNM 2009. Evidence of measurable local recurrence at the prostate bed detected by PSMA PET/CT and mpMRI within the last 3 months. In case of unclear local recurrence, a biopsy confirmation is recommended. Patient must have non-metastatic (N0, M0) disease, as defined by a lack of nodal or distant metastases seen on PSMA PET/CT scan Patients must have non-castrate levels of serum testosterone (≥50 ng/dL). Patients must not have previously received hormonal therapy (LHRH agonists, antiandrogen, or both, or bilateral orchiectomy). Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial Exclusion Criteria: Persistent PSA (> 0.4 ng/mL) 4 to 20 weeks after RP Previous hematologic or primary solid malignancy within 3 years prior registration with the exception of curatively treated localized non-melanoma skin cancer Usage of products known to affect PSA levels within 4 weeks prior to start of trial treatment phase including any form of androgen suppression agents and androgen deprivation therapy Bilateral hip prosthesis Severe or active co-morbidity likely to impact on the advisability of SRT Treatment with any experimental drug or participation within a clinical trial within 30 days prior to registration (exception: concurrent participation in the biobank studies is allowed)

Sites / Locations

  • Inselgruppe AG, InselspitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm

Arm Description

Patients with locally recurred prostate cancer will receive a ultrahypofractionated stereotactic radiotherapy to the radiologically identified lesion (Dose: 5 fractions with 7Gray every second work week day) combined with an androgen deprivation therapy (LHRH-agonist / -antagonist) for 6 months.

Outcomes

Primary Outcome Measures

Biochemical relapsefree survival
The initial prostate specific antigen (PSA) at time of registration will be the starting point. Freedom from biochemical progression is counted from the day of registration to the day of either first recorded biochemical progression as defined below, clinical progression or death due to clinical progression. Biochemical relapsefree survival measured with PSA (prostate specific antigen) lab testing at 1, 3, 6, 12, 18 and 24 months after radiotherapy. The duration of biochemical relapsefree survival is measured and documented in months for each patient. A biochemical recurrence is defined by any confirmed PSA rise above 0.20 ng/mL with a confirmatory rise at least 2 weeks later. For those patients whose PSA does not drop below 0.20 ng/mL at time of first response assessment at 3 months are considered as non-responders to treatment and are considered to have a biochemical recurrence in case a second measurement at least 2 weeks later confirms a rising PSA above this level.

Secondary Outcome Measures

Acute side effects of grade 3 or higher
Standard acquisition of therapy related acute side effects of grade 3 or higher according to NCI CTCAE v5.0 at radiotherapy end and at 1 and 3 months after radiotherapy will be assessed. The side effects are recorded with the corresponding grade according to the NCI CTCAE v5.0 scale at the measured points of time. Special attention shall be given to diarrhea, fecal incontinence, proctitis, rectal hemorrhage, rectal pain, hematuria, urinary frequency, urinary urgency, urinary retention, urinary incontinence, cystitis non-infective and erectile dysfunction.
Clinical progression-free survival
Clinical progression-free survival is defined as time between registration and the appearance of a new recurrence (any N1 or M1) as suggested by PET-CT, symptoms related to progressive prostate cancer (PC), or death due to any cause. The duration of clinical progression-free survival is measured and documented in months for each patient. Definition of recurrence: A local recurrence is defined as the appearance of evidence of a recurrence within the prostate bed. Confirmation of the recurrence by biopsy is recommended, whenever possible. A regional nodal recurrence is defined as a radiographic (PET-CT) evidence of a lymphadenopathy in the pelvis in a patient without the diagnosis of hematologic/lymphatic disorder Distant recurrence is defined as the appearance of distant metastases (M1a, M1b, M1c) outside the pelvis.
Metastasis-free survival
Metastasis-free survival is defined as time between registration and the appearance of a metastatic recurrence (any M1) as suggested by PET-CT or death due to any cause. The duration of metastasis-free survival is measured and documented in months for each patient. Patients without any of the events of interest (including those with biochemical relapse only) are censored at the date of the last follow-up. Second cancers are not considered events in terms of this endpoint. In case of biochemical progression, re-staging will be made with PET-CT imaging preferably with the same tracer used before registration. In case of negative PET findings at biochemical relapse, a new PET imaging should be repeated on a 6-monthly basis or earlier in case clinically indicated.
Late side effects
Standard acquisition of therapy related late side effects according to NCI CTCAE v5.0 at 6, 12, 18 and 24 months after radiotherapy. The side effects are recorded with the corresponding grade according to the NCI CTCAE v5.0 scale at the measured points of time. Special attention shall be given to diarrhea, fecal incontinence, proctitis, rectal hemorrhage, rectal pain, hematuria, urinary frequency, urinary urgency, urinary retention, urinary incontinence, cystitis non-infective and erectile dysfunction.
Quality of life (EORTC Quality of life questionnaire C-30 version 3)
All patients registered into this trial are to complete QoL questionnaires at registration and at 1, 3, 6, 12, 18, 24 months after radiotherapy. A longitudinal design is used. Patients are asked to complete the EORTC Quality of life questionnaire C-30 version 3. The resulting score will be documented at each point of time.
Quality of life ( EORTC Quality of life PR25)
All patients registered into this trial are to complete QoL questionnaires at registration and at 1, 3, 6, 12, 18, 24 months after radiotherapy. A longitudinal design is used. Patients are asked to complete the EORTC Quality of life questionnaire PR25 prostate cancer module. The resulting score will be documented at each point of time.

Full Information

First Posted
February 16, 2023
Last Updated
May 11, 2023
Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
University of Bern, Debiopharm International SA, Werner und Hedy Berger-Janser - Stiftung
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1. Study Identification

Unique Protocol Identification Number
NCT05746806
Brief Title
Trial of Ultrahypofractionated Focal Salvage Radiotherapy for Isolated Prostate Bed Recurrence After Radical Prostatectomy
Acronym
HypoFocal SRT
Official Title
A Single Arm Phase II Trial of Ultrahypofractionated Focal Salvage Radiotherapy for Isolated Prostate Bed Recurrence After Radical Prostatectomy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 29, 2023 (Actual)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
August 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
University of Bern, Debiopharm International SA, Werner und Hedy Berger-Janser - Stiftung

4. Oversight

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

5. Study Description

Brief Summary
The main objective of the trial is to explore the efficacy and safety of combining short-term androgen deprivation therapy (ADT) over 6 months to focal ultrahypofractionated salvage radiotherapy (SRT) delivered in 5 fractions to the site of local recurrence within the prostate bed after radical prostatectomy where multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) PET/CT are used to precisely identify the local recurrence and compare it to previously published literature.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Prostate Cancer
Keywords
Prostate, Salvage Radiation, Local recurrence, Stereotactic radiotherapy, Hypofractionation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single arm
Arm Type
Experimental
Arm Description
Patients with locally recurred prostate cancer will receive a ultrahypofractionated stereotactic radiotherapy to the radiologically identified lesion (Dose: 5 fractions with 7Gray every second work week day) combined with an androgen deprivation therapy (LHRH-agonist / -antagonist) for 6 months.
Intervention Type
Radiation
Intervention Name(s)
Ultrahypofractionated salvage radiotherapy to a local recurrence after radical prostatectomy
Intervention Description
Ultrahypofractioned radiotherapy for patients with isolated local recurrence after radical prostatectomy in 5 fractions
Intervention Type
Drug
Intervention Name(s)
Androgen deprivation therapy
Intervention Description
In combination to the radiotherapy a short term androgen deprivation drug for 6 months will be applied. The drug concept used is: - LHRH(Luteinizing hormone releasing hormone)-agonist with 3-month subcutaneous depot injection (e.g. Pamorelin® LA (Triptorelin) 11.25mg s.c.) in combination with nonsteroidal antiandrogen (e.g. Bicalutamide 50mg/day) as flare protection at least 5 days before and max. 15 days after first LHRH-injection
Primary Outcome Measure Information:
Title
Biochemical relapsefree survival
Description
The initial prostate specific antigen (PSA) at time of registration will be the starting point. Freedom from biochemical progression is counted from the day of registration to the day of either first recorded biochemical progression as defined below, clinical progression or death due to clinical progression. Biochemical relapsefree survival measured with PSA (prostate specific antigen) lab testing at 1, 3, 6, 12, 18 and 24 months after radiotherapy. The duration of biochemical relapsefree survival is measured and documented in months for each patient. A biochemical recurrence is defined by any confirmed PSA rise above 0.20 ng/mL with a confirmatory rise at least 2 weeks later. For those patients whose PSA does not drop below 0.20 ng/mL at time of first response assessment at 3 months are considered as non-responders to treatment and are considered to have a biochemical recurrence in case a second measurement at least 2 weeks later confirms a rising PSA above this level.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Acute side effects of grade 3 or higher
Description
Standard acquisition of therapy related acute side effects of grade 3 or higher according to NCI CTCAE v5.0 at radiotherapy end and at 1 and 3 months after radiotherapy will be assessed. The side effects are recorded with the corresponding grade according to the NCI CTCAE v5.0 scale at the measured points of time. Special attention shall be given to diarrhea, fecal incontinence, proctitis, rectal hemorrhage, rectal pain, hematuria, urinary frequency, urinary urgency, urinary retention, urinary incontinence, cystitis non-infective and erectile dysfunction.
Time Frame
90 days
Title
Clinical progression-free survival
Description
Clinical progression-free survival is defined as time between registration and the appearance of a new recurrence (any N1 or M1) as suggested by PET-CT, symptoms related to progressive prostate cancer (PC), or death due to any cause. The duration of clinical progression-free survival is measured and documented in months for each patient. Definition of recurrence: A local recurrence is defined as the appearance of evidence of a recurrence within the prostate bed. Confirmation of the recurrence by biopsy is recommended, whenever possible. A regional nodal recurrence is defined as a radiographic (PET-CT) evidence of a lymphadenopathy in the pelvis in a patient without the diagnosis of hematologic/lymphatic disorder Distant recurrence is defined as the appearance of distant metastases (M1a, M1b, M1c) outside the pelvis.
Time Frame
2 years
Title
Metastasis-free survival
Description
Metastasis-free survival is defined as time between registration and the appearance of a metastatic recurrence (any M1) as suggested by PET-CT or death due to any cause. The duration of metastasis-free survival is measured and documented in months for each patient. Patients without any of the events of interest (including those with biochemical relapse only) are censored at the date of the last follow-up. Second cancers are not considered events in terms of this endpoint. In case of biochemical progression, re-staging will be made with PET-CT imaging preferably with the same tracer used before registration. In case of negative PET findings at biochemical relapse, a new PET imaging should be repeated on a 6-monthly basis or earlier in case clinically indicated.
Time Frame
2 years
Title
Late side effects
Description
Standard acquisition of therapy related late side effects according to NCI CTCAE v5.0 at 6, 12, 18 and 24 months after radiotherapy. The side effects are recorded with the corresponding grade according to the NCI CTCAE v5.0 scale at the measured points of time. Special attention shall be given to diarrhea, fecal incontinence, proctitis, rectal hemorrhage, rectal pain, hematuria, urinary frequency, urinary urgency, urinary retention, urinary incontinence, cystitis non-infective and erectile dysfunction.
Time Frame
After 90 days up to 2 years (after acute side effects, see outcome 2)
Title
Quality of life (EORTC Quality of life questionnaire C-30 version 3)
Description
All patients registered into this trial are to complete QoL questionnaires at registration and at 1, 3, 6, 12, 18, 24 months after radiotherapy. A longitudinal design is used. Patients are asked to complete the EORTC Quality of life questionnaire C-30 version 3. The resulting score will be documented at each point of time.
Time Frame
2 years
Title
Quality of life ( EORTC Quality of life PR25)
Description
All patients registered into this trial are to complete QoL questionnaires at registration and at 1, 3, 6, 12, 18, 24 months after radiotherapy. A longitudinal design is used. Patients are asked to complete the EORTC Quality of life questionnaire PR25 prostate cancer module. The resulting score will be documented at each point of time.
Time Frame
2 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent according to ICH/GCP (International Council for Harmonisation/Good Clinical Practice) regulations before registration and prior to any trial specific procedures Age ≥ 18 years at time of registration WHO performance status 0-1 Lymph node negative adenocarcinoma of the prostate treated with radical prostatectomy (RP) at least 6 months before trial Tumor stage pT2a-3b, R0-1, pN0 or cN0 according to the Union for International Cancer Control (UICC) TNM 2009. Evidence of measurable local recurrence at the prostate bed detected by PSMA PET/CT and mpMRI within the last 3 months. In case of unclear local recurrence, a biopsy confirmation is recommended. Patient must have non-metastatic (N0, M0) disease, as defined by a lack of nodal or distant metastases seen on PSMA PET/CT scan Patients must have non-castrate levels of serum testosterone (≥50 ng/dL). Patients must not have previously received hormonal therapy (LHRH agonists, antiandrogen, or both, or bilateral orchiectomy). Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial Exclusion Criteria: Persistent PSA (> 0.4 ng/mL) 4 to 20 weeks after RP Previous hematologic or primary solid malignancy within 3 years prior registration with the exception of curatively treated localized non-melanoma skin cancer Usage of products known to affect PSA levels within 4 weeks prior to start of trial treatment phase including any form of androgen suppression agents and androgen deprivation therapy Bilateral hip prosthesis Severe or active co-morbidity likely to impact on the advisability of SRT Treatment with any experimental drug or participation within a clinical trial within 30 days prior to registration (exception: concurrent participation in the biobank studies is allowed)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mohamed MS Shelan, Assistant Professor
Phone
+41316322632
Email
mohamed.shelan@insel.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mohamed MS Shelan, PD
Organizational Affiliation
Department of radiation oncology, Bern University Hospital, Inselspital, Berne, Switzerland
Official's Role
Study Director
Facility Information:
Facility Name
Inselgruppe AG, Inselspital
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohamed MS Shelan, PD
Phone
+41316322632
Email
mohamed.shelan@insel.ch
First Name & Middle Initial & Last Name & Degree
Mohamed MS Shelan, PD

12. IPD Sharing Statement

Plan to Share IPD
No

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Trial of Ultrahypofractionated Focal Salvage Radiotherapy for Isolated Prostate Bed Recurrence After Radical Prostatectomy

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