Prostate PMSABR Study
Primary Purpose
Prostate Cancer
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
SABR
SOC
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
- Histological confirmation of prostate adenocarcinoma
- Evidence of stage IV disease (as defined by AJCC criteria) on previous bone, CT, and/or MRI scan
- Ongoing ADT with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy (ie, surgical or medical castration) confirmed by testosterone level ≤ 1.73 nmol/L (50 ng/dL) at the screening visit
- ECOG performance score 0-2
- Age ≥ 18
- History/physical examination within 2 weeks prior to registration
- Able to sign informed-consent
- Patient with mCRPC who received Enzalutamide during the past 6-8 weeks and must have been delivered for a total of at least 3 months with an initial ≥50% decline of PSA from baseline.
Documented disease progression with Enzalutamide as defined by PCWG3 with at least one of the followings:
- PSA progression: defined by PSA increase that is ≥ 25% and ≥ 2 ng/mL above the nadir. A minimum of 2 rising PSA levels with an interval of ≥ 1 week between each determination.
- Radiographic disease progression in soft tissue based on RECIST 1.1 criteria. Participants whose disease spread is limited to regional pelvic lymph nodes (N1) measuring at least 2 cm in short axis will be considered eligible.
- Radiographic disease progression in bone defined as appearance of 2 or more new bone lesions on bone scan
- A maximum of 5 extracranial metastases in any organ system (except brain), with ≤ 4 tumours within any given organ system, confirmed with PSMA PET-CT scan
- All sites of oligometastasis can be safely treated with SABR
- Adequate baseline organ function to allow SABR to all relevant targets
- Participants already receiving agents for the management of skeletal-related events (SREs) are allowed to continue with anti-bone resorptive therapy (including, but not limited to bisphosphonate or receptor activator of nuclear factor kappa ligand inhibitor) if on stable dose for more than 28 days prior to treatment arm assignment
Exclusion Criteria:
- Patients with active cancer other than prostate cancer and non-melanoma skin cancer.
- Prior treatment with docetaxel, another chemotherapy agent or second generation hormonal therapy (e.g. abiraterone acetate or enzalutamide) for metastatic castration-resistant prostate cancer. Prior docetaxel, abiraterone acetate or enzalutamide for metastatic hormone-sensitive prostate cancer is allowed if ≥ 12 months elapsed from last dose of these treatments.
- PSA at inclusion >20 ng/ml
- Serum creatinine and total bilirubin > 3 times the upper limit of normal
- Liver Transaminases > 5-times the upper limit of normal
- Unstable angina and/or congestive heart failure requiring hospitalization, transmural myocardial infarction within the last 6 months, acute bacterial or fungal infection requiring intravenous antibiotics, chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
- Patients with oligometastases that have been previously treated with SABR.
- Serious medical comorbidities precluding radiotherapy, such as ataxia-telangiectasia or scleroderma. For patients with oligoprogressive lesions in the lung or thorax, this includes interstitial lung disease
- Clinical or radiological evidence of spinal cord compression or tumor within 1.5mm of spinal cord on MRI
- Malignant pleural effusion
- Malignant peritoneal disease
- Intra-cranial metastases
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
SABR
SOC
Arm Description
Outcomes
Primary Outcome Measures
The 6-month progression-Free Survival rate
Secondary Outcome Measures
Progression-Free Survival
Time to progression
Overall survival
Local control rate of the SABR-treated oligometastasis at 6 months after SABR
Local control rate of the SABR-treated oligometastasis at 6 months after SABR based on the PERCIST criteria
QOL (EORTC QLQ-C30)
Time to next systemic treatment
The number of participants with treatment-related adverse event as assessed by CTCAE v4.0
The proportion of patients in both arms who have AR-V7 (CTCs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04742972
Brief Title
Prostate PMSABR Study
Official Title
PSMA-PET Guided Stereotactic Ablative Body Radiotherapy for Oligometastasis in Metastatic Castration-resistant Prostate Cancer (mCRPC) With Progression on Enzalutamide (PMSABR Study)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Withdrawn
Why Stopped
The lack of well-defined oligometastasis, high disease burden in mCRPC and high sensitivity of PSMA-PET scan, PMSABR study was made with high ambition and the assumption on recruitment was found to be invalid.
Study Start Date
February 25, 2021 (Actual)
Primary Completion Date
September 15, 2022 (Actual)
Study Completion Date
September 16, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Darren Poon
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
In this study, the investigator aim to evaluate the role of PMSA-PET guided SABR on progression free survival (PFS) in patients with oligoprogressive mCRPC with Enzalutamide. The potential improvement in PFS with SABR while continuing the initial-responding Enzalutamide is potentially benefiting to patients in terms of overall disease control.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SABR
Arm Type
Experimental
Arm Title
SOC
Arm Type
Placebo Comparator
Intervention Type
Radiation
Intervention Name(s)
SABR
Intervention Description
SABR is delivered to all sites of oligometastasis with continuation of Enzalutamide. Further oligo-progressive lesions may be treated with SABR if possible. Upon progression at sites not amenable to SABR, the patient may receive any of the options in SOC Arm.
Intervention Type
Other
Intervention Name(s)
SOC
Intervention Description
Three options:
Continuation of Enzalutamide
Observation
Switch to next line treatment
Primary Outcome Measure Information:
Title
The 6-month progression-Free Survival rate
Time Frame
up to 2 years
Secondary Outcome Measure Information:
Title
Progression-Free Survival
Time Frame
2 years
Title
Time to progression
Time Frame
2 years
Title
Overall survival
Time Frame
2 years
Title
Local control rate of the SABR-treated oligometastasis at 6 months after SABR
Time Frame
up to 2 years
Title
Local control rate of the SABR-treated oligometastasis at 6 months after SABR based on the PERCIST criteria
Time Frame
up to 2 years
Title
QOL (EORTC QLQ-C30)
Time Frame
2 years
Title
Time to next systemic treatment
Time Frame
2 years
Title
The number of participants with treatment-related adverse event as assessed by CTCAE v4.0
Time Frame
2 years
Title
The proportion of patients in both arms who have AR-V7 (CTCs)
Time Frame
2 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histological confirmation of prostate adenocarcinoma
Evidence of stage IV disease (as defined by AJCC criteria) on previous bone, CT, and/or MRI scan
Ongoing ADT with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy (ie, surgical or medical castration) confirmed by testosterone level ≤ 1.73 nmol/L (50 ng/dL) at the screening visit
ECOG performance score 0-2
Age ≥ 18
History/physical examination within 2 weeks prior to registration
Able to sign informed-consent
Patient with mCRPC who received Enzalutamide during the past 6-8 weeks and must have been delivered for a total of at least 3 months with an initial ≥50% decline of PSA from baseline.
Documented disease progression with Enzalutamide as defined by PCWG3 with at least one of the followings:
PSA progression: defined by PSA increase that is ≥ 25% and ≥ 2 ng/mL above the nadir. A minimum of 2 rising PSA levels with an interval of ≥ 1 week between each determination.
Radiographic disease progression in soft tissue based on RECIST 1.1 criteria. Participants whose disease spread is limited to regional pelvic lymph nodes (N1) measuring at least 2 cm in short axis will be considered eligible.
Radiographic disease progression in bone defined as appearance of 2 or more new bone lesions on bone scan
A maximum of 5 extracranial metastases in any organ system (except brain), with ≤ 4 tumours within any given organ system, confirmed with PSMA PET-CT scan
All sites of oligometastasis can be safely treated with SABR
Adequate baseline organ function to allow SABR to all relevant targets
Participants already receiving agents for the management of skeletal-related events (SREs) are allowed to continue with anti-bone resorptive therapy (including, but not limited to bisphosphonate or receptor activator of nuclear factor kappa ligand inhibitor) if on stable dose for more than 28 days prior to treatment arm assignment
Exclusion Criteria:
Patients with active cancer other than prostate cancer and non-melanoma skin cancer.
Prior treatment with docetaxel, another chemotherapy agent or second generation hormonal therapy (e.g. abiraterone acetate or enzalutamide) for metastatic castration-resistant prostate cancer. Prior docetaxel, abiraterone acetate or enzalutamide for metastatic hormone-sensitive prostate cancer is allowed if ≥ 12 months elapsed from last dose of these treatments.
PSA at inclusion >20 ng/ml
Serum creatinine and total bilirubin > 3 times the upper limit of normal
Liver Transaminases > 5-times the upper limit of normal
Unstable angina and/or congestive heart failure requiring hospitalization, transmural myocardial infarction within the last 6 months, acute bacterial or fungal infection requiring intravenous antibiotics, chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
Patients with oligometastases that have been previously treated with SABR.
Serious medical comorbidities precluding radiotherapy, such as ataxia-telangiectasia or scleroderma. For patients with oligoprogressive lesions in the lung or thorax, this includes interstitial lung disease
Clinical or radiological evidence of spinal cord compression or tumor within 1.5mm of spinal cord on MRI
Malignant pleural effusion
Malignant peritoneal disease
Intra-cranial metastases
12. IPD Sharing Statement
Plan to Share IPD
No
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Prostate PMSABR Study
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