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Stereotactic Body Radiotherapy With or Without Darolutamide for OligoRecurrent Prostate Cancer (DART)

Primary Purpose

Prostate Cancer, Prostate Cancer Recurrent, Prostate Cancer Metastatic

Status
Recruiting
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Darolutamide
metastasis-directed treatment
Sponsored by
University Hospital, Ghent
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Radiotherapy, Metastasis-directed therapy, Oligometastatic recurrent hormone sensitive prostate cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically proven initial diagnosis of adenocarcinoma of the prostate
  • Biochemical relapse of PCa following radical local prostate treatment (radical prostatectomy (RP), primary radiotherapy or the combination of RP and prostate bed adjuvant/ salvage radiotherapy) according to the EAU guidelines 2018.
  • Following RP, patients with a biochemical relapse are eligible in case a metastatic relapse is detected even in the absence of prior postoperative prostate bed radiotherapy (adjuvant or salvage). In the absence of prior prostate bed radiotherapy, prostate bed radiotherapy is mandatory for all pT3a or higher or patients with a positive margin at time of RP.
  • For patients without prior RP that have a suspected local recurrence following primary radiotherapy, a biopsy should confirm local recurrence. Patients with a confirmed local recurrence and metastases are eligible in case they also undergo a local salvage therapy.
  • Metastatic relapse on PSMA PET-CT with a maximum of 5 metastases (any M1a, M1b or M1c). Concomitant diagnosis of N1 disease is allowed as long as all lesions are treated with SBRT and the total number of lesions does not exceed 5. PSMA positive lesions will be scored using the MI-RADS scoring system with lesions scored 4 or 5 considered positive19.
  • Asymptomatic for metastatic PCa
  • Age >= 18 years
  • WHO class 0-1
  • 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
  • Before patient registration/randomization, written informed consent must be given in accordance with to ICH/GCP, and national/local regulations.

Exclusion Criteria:

  • Local relapse in the prostate gland or prostate bed not suitable for a local salvage treatment
  • Small cell carcinoma of the prostate
  • PSA doubling time >12 months
  • Serum testosterone level <50ng/dl or 1.7 nmol/L at time of randomization
  • Currently receiving ADT or PSA rise while on active treatment with ADT (LHRH-agonist, LHRH-antagonist, anti-androgen or estrogen) within the past 6 weeks
  • Spinal cord compression or impending spinal cord compression
  • Metastases in previously irradiated areas precluding safe delivery of SBRT
  • Contraindications to darolutamide
  • Previous treatment with cytotoxic agent for PCa
  • Treatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids,…)
  • Other active malignancy, except non-melanoma skin cancer or other malignancies with a documented disease-free survival for a minimum of 3 years.

Sites / Locations

  • OLVZ AalstRecruiting
  • GZARecruiting
  • AZ St-Jan BruggeRecruiting
  • Institut Jules BordetRecruiting
  • AZ St-Lucas GentRecruiting
  • Ghent University HospitalRecruiting
  • Jessa ZiekenhuisRecruiting
  • AZ GroeningeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Arm A

Arm B

Arm Description

SBRT + 6 months of darolutamide (600 mg b.i.d.)

SBRT only

Outcomes

Primary Outcome Measures

Metastasis-free survival
Metastasis-free survival is defined as time between randomization and the appearance of a new metastatic recurrence (any M1) as suggested by PET-CT or death due to any cause.

Secondary Outcome Measures

Clinical progression-free survival
Clinical progression-free survival is defined as the time between randomization and the appearance of a new lesion (any N1 or M1), a local recurrence as suggested by PET-CT, symptoms related to progressive PCa, or death due to any cause.
Biochemical relapse-free survival
For patients who had previous RP at initial diagnosis, 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 patients who had previous RT to the prostate at initial diagnosis, a biochemical recurrence is defined as the nadir + 2ng/ml (Phoenix definition). Non-responders are considered to have a biochemical recurrence in case a second measurement at least 2 weeks later confirms a rising PSA
Time to next systemic therapy
Time to next systemic therapy is defined as the initiation of any PCa systemic treatment. Systemic therapy will typically be initiated on progression and/or development of new metastases, but indications are at the discretion of the physician.
Castrate resistant-free survival
Time to castration resistant disease is defined as the time from trial randomization until castration resistant status
Prostate cancer-specific survival
PCa-specific survival will be read as the time from trial randomization to the date of death due to PCa.
Overall survival
Overall survival will be read as the time from trial randomization to the date of death from any cause.
Toxicity: acute toxicity
Radiotherapy toxicity will be assessed according to NCI CTCAE v5.0.
Toxicity: late toxicity
Radiotherapy toxicity will be assessed according to NCI CTCAE v5.0.
Patient reported QOL as per EORTC-QLQ C30
Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients. A higher score of a symptom scale or item indicates a worse condition; a higher score of a functional scale or global health status/QoL indicates a better condition. A clinically meaningful change is defined as a change from baseline of at least 10 points (i.e., about one-half standard deviation) in either direction.
Patient reported QOL as per EORTC-QLQ PR25
Validated questionnaire assessing the health-related QOL of prostate cancer patients. A higher score of a symptom scale or item indicates a worse condition; a higher score of a functional scale or global health status/QoL indicates a better condition. A clinically meaningful change is defined as a change from baseline of at least 10 points (i.e., about one-half standard deviation) in either direction.

Full Information

First Posted
November 17, 2020
Last Updated
February 3, 2023
Sponsor
University Hospital, Ghent
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1. Study Identification

Unique Protocol Identification Number
NCT04641078
Brief Title
Stereotactic Body Radiotherapy With or Without Darolutamide for OligoRecurrent Prostate Cancer
Acronym
DART
Official Title
Stereotactic Body Radiotherapy With or Without Darolutamide for OligoRecurrent Prostate Cancer: a Randomized Phase II Trial (DART)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 12, 2021 (Actual)
Primary Completion Date
February 12, 2026 (Anticipated)
Study Completion Date
February 12, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Ghent

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The current trial will test the combination of darolutamide with SBRT, in oligometastatic recurrent hormone sensitive prostate cancer. We hypothesize that the addition of short-term darolutamide improves metastasis-free survival when added to SBRT without a detrimental impact on the QoL. Considering the large reluctance of both patients and physicians to be randomized to observation, we propose to use the historical data from previous reported randomized trials (STOMP and ORIOLE) as a comparator to explore as a secondary endpoint.
Detailed Description
As of the 2018 EAU guidelines, PSMA PET-CT is now recommended for prostate cancer patients with a rising PSA following local therapy, resulting in an increase in patients with conventional imaging M0, but novel imaging M1-state. This creates a new class of patients for which no clear guidelines exist on the optimal management. It became clear that there is no real consensus nor data on how these patients should be treated. In 1995, a new approach was proposed, hypothesizing that patients with a limited number of metastases (oligometastases) might benefit from eradication of metastases by means of local therapy, or metastasis-directed therapy. Stereotactic body radiotherapy (SBRT), a novel radiotherapy technique for metastatic and primary prostate cancer treatments, has emerged as a highly precise radiotherapy method able to eradicate small metastases with acceptable toxicity. Nevertheless, responses following SBRT were not always durable. To improve response rates and time to new metastases, additional steps should be taken balancing with potential added toxicity. One of the logical steps would be to combine SBRT with temporary androgen deprivation therapy (ADT) as this combination therapy is standard of care for primary PCa and locally recurrent PCa17. However, ADT, negatively impacts quality of life (QoL) even when used temporary. Anti-androgen or androgen receptor (AR) pathway inhibitors (ARpI) may circumvent these side effects by suppressing AR transcription by competitive inhibition of AR, without lowering systemic testosterone. The current trial will test the combination of darolutamide with SBRT, in oligometastatic recurrent hormone sensitive prostate cancer. We hypothesize that the addition of short-term darolutamide improves metastasis-free survival when added to SBRT without a detrimental impact on the QoL.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Prostate Cancer Recurrent, Prostate Cancer Metastatic, Metastatic Cancer, Oligometastasis
Keywords
Radiotherapy, Metastasis-directed therapy, Oligometastatic recurrent hormone sensitive prostate cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
124 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
SBRT + 6 months of darolutamide (600 mg b.i.d.)
Arm Title
Arm B
Arm Type
Other
Arm Description
SBRT only
Intervention Type
Drug
Intervention Name(s)
Darolutamide
Intervention Description
600 mg BID
Intervention Type
Radiation
Intervention Name(s)
metastasis-directed treatment
Intervention Description
stereotactic body radiotherapy
Primary Outcome Measure Information:
Title
Metastasis-free survival
Description
Metastasis-free survival is defined as time between randomization and the appearance of a new metastatic recurrence (any M1) as suggested by PET-CT or death due to any cause.
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Clinical progression-free survival
Description
Clinical progression-free survival is defined as the time between randomization and the appearance of a new lesion (any N1 or M1), a local recurrence as suggested by PET-CT, symptoms related to progressive PCa, or death due to any cause.
Time Frame
2 year
Title
Biochemical relapse-free survival
Description
For patients who had previous RP at initial diagnosis, 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 patients who had previous RT to the prostate at initial diagnosis, a biochemical recurrence is defined as the nadir + 2ng/ml (Phoenix definition). Non-responders are considered to have a biochemical recurrence in case a second measurement at least 2 weeks later confirms a rising PSA
Time Frame
2 year
Title
Time to next systemic therapy
Description
Time to next systemic therapy is defined as the initiation of any PCa systemic treatment. Systemic therapy will typically be initiated on progression and/or development of new metastases, but indications are at the discretion of the physician.
Time Frame
4 year
Title
Castrate resistant-free survival
Description
Time to castration resistant disease is defined as the time from trial randomization until castration resistant status
Time Frame
4 year
Title
Prostate cancer-specific survival
Description
PCa-specific survival will be read as the time from trial randomization to the date of death due to PCa.
Time Frame
4 year
Title
Overall survival
Description
Overall survival will be read as the time from trial randomization to the date of death from any cause.
Time Frame
4 year
Title
Toxicity: acute toxicity
Description
Radiotherapy toxicity will be assessed according to NCI CTCAE v5.0.
Time Frame
3 months
Title
Toxicity: late toxicity
Description
Radiotherapy toxicity will be assessed according to NCI CTCAE v5.0.
Time Frame
2 year
Title
Patient reported QOL as per EORTC-QLQ C30
Description
Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients. A higher score of a symptom scale or item indicates a worse condition; a higher score of a functional scale or global health status/QoL indicates a better condition. A clinically meaningful change is defined as a change from baseline of at least 10 points (i.e., about one-half standard deviation) in either direction.
Time Frame
2 year
Title
Patient reported QOL as per EORTC-QLQ PR25
Description
Validated questionnaire assessing the health-related QOL of prostate cancer patients. A higher score of a symptom scale or item indicates a worse condition; a higher score of a functional scale or global health status/QoL indicates a better condition. A clinically meaningful change is defined as a change from baseline of at least 10 points (i.e., about one-half standard deviation) in either direction.
Time Frame
2 year

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically proven initial diagnosis of adenocarcinoma of the prostate Biochemical relapse of PCa following radical local prostate treatment (radical prostatectomy (RP), primary radiotherapy or the combination of RP and prostate bed adjuvant/ salvage radiotherapy) according to the EAU guidelines 2018. Following RP, patients with a biochemical relapse are eligible in case a metastatic relapse is detected even in the absence of prior postoperative prostate bed radiotherapy (adjuvant or salvage). In the absence of prior prostate bed radiotherapy, prostate bed radiotherapy is mandatory for all pT3a or higher or patients with a positive margin at time of RP. For patients without prior RP that have a suspected local recurrence following primary radiotherapy, a biopsy should confirm local recurrence. Patients with a confirmed local recurrence and metastases are eligible in case they also undergo a local salvage therapy. Metastatic relapse on PSMA PET-CT with a maximum of 5 metastases (any M1a, M1b or M1c). Concomitant diagnosis of N1 disease is allowed as long as all lesions are treated with SBRT and the total number of lesions does not exceed 5. PSMA positive lesions will be scored using the MI-RADS scoring system with lesions scored 4 or 5 considered positive19. Asymptomatic for metastatic PCa Age >= 18 years WHO class 0-1 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 Before patient registration/randomization, written informed consent must be given in accordance with to ICH/GCP, and national/local regulations. Exclusion Criteria: Local relapse in the prostate gland or prostate bed not suitable for a local salvage treatment Small cell carcinoma of the prostate PSA doubling time >12 months Serum testosterone level <50ng/dl or 1.7 nmol/L at time of randomization Currently receiving ADT or PSA rise while on active treatment with ADT (LHRH-agonist, LHRH-antagonist, anti-androgen or estrogen) within the past 6 weeks Spinal cord compression or impending spinal cord compression Metastases in previously irradiated areas precluding safe delivery of SBRT Contraindications to darolutamide Previous treatment with cytotoxic agent for PCa Treatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids,…) Other active malignancy, except non-melanoma skin cancer or other malignancies with a documented disease-free survival for a minimum of 3 years.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Piet Ost, MD, PhD
Phone
003293323015
Email
piet.ost@ugent.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Piet Ost, MD, PhD
Organizational Affiliation
University Hospital, Ghent
Official's Role
Principal Investigator
Facility Information:
Facility Name
OLVZ Aalst
City
Aalst
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ruben De Groote, MD
Facility Name
GZA
City
Antwerp
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Piet Dirix, MD
Facility Name
AZ St-Jan Brugge
City
Brugge
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sabine Meersschout, MD
Facility Name
Institut Jules Bordet
City
Brussel
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
François-Xavier Otte, MD
Facility Name
AZ St-Lucas Gent
City
Gent
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lien Van De Voorde, MD
Facility Name
Ghent University Hospital
City
Ghent
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Piet Ost, MD, PhD
Facility Name
Jessa Ziekenhuis
City
Hasselt
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leen Noé, MD
Facility Name
AZ Groeninge
City
Kortrijk
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Siska Van Bruwaene, MD

12. IPD Sharing Statement

Learn more about this trial

Stereotactic Body Radiotherapy With or Without Darolutamide for OligoRecurrent Prostate Cancer

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