Prostatic NeoplasmsPhase 2DEFINENCT05851547
Dose Escalation For INtraprostatic LEsions
A Phase 2 study testing Prostate SBRT with Focal Boost and Triptorelin Injection in people with Prostatic Neoplasms, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
External beam radiotherapy combined with androgen deprivation therapy is a standard treatment option for localized prostate cancer. The current standard involves delivering radiotherapy uniformly throughout the prostate gland in daily fractions, five days per week, for approximately four weeks. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- Prostate SBRT with Focal Boost and Triptorelin Injection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteCanada
- Study dates
- 23 Nov 2023to Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed adenocarcinoma of the prostate
- Unfavourable intermediate-risk or high-risk localized disease
- Unfavourable intermediate-risk prostate cancer is defined as intermediate-risk prostate cancer [that is, no high-risk features and one or more intermediate-risk factors: T2b-T2c, Gleason 3+4 (grade group 2) or Gleason 4+3 (grade group 3), or PSA 10-20 μg/L] and one or more of the following: 2 or 3 intermediate-risk factors; Gleason 4+3 (grade group 3); ≥ 50% biopsy cores positive
- High-risk localized prostate cancer is defined as at least one of the following: T3a-T3b; Gleason ≥ 8 (grade group 4 or grade group 5); PSA > 20 μg/L
- 3 Tesla prostate MRI done no more than 12 months prior to enrollment
- ECOG performance status 0-2
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- Age ≥ 18 years
- Written informed consent
- The participant has planned androgen deprivation therapy that meets one of the following criteria:
- Patients with intermediate-risk localized prostate cancer who have planned androgen deprivation therapy consisting of up to 6 months of triptorelin with or without bicalutamide; OR patients with high-risk localized prostate cancer who have planned androgen deprivation therapy consisting of up to 24 months of triptorelin with or without bicalutamide.
- Completion of all appropriate investigations prior to enrollment
Who cannot join
- Evidence of pelvic nodal metastases or distant metastases (AJCC Stage T1-4 N1 M0-1 or T1-4 N0 M1 disease)
- Discordance between pre-enrollment prostate MRI and prostate biopsy findings, defined as biopsy cores with Gleason Gleason ≥ 4+3 (grade group ≥ 3) adenocarcinoma with no corresponding tumour focus seen on MRI
- Androgen deprivation therapy commenced more than 60 days prior to enrollment
- Intention to electively treat the pelvic lymph nodes with radiotherapy
- Other active malignancy within the previous three years (except adequately treated nonmelanomatous carcinoma of the skin or low-grade superficial bladder carcinoma)
- Prior pelvic radiotherapy
Show all 11Show fewer
- Contraindication to pelvic radiotherapy
- Any history, past or present, of inflammatory bowel disease
- Unilateral or bilateral hip arthroplasty
- Trans-urethral resection of the prostate (TURP) performed within 6 months of anticipated start date of radiotherapy
- Patients must not concurrently participate in any other therapeutic prostate cancer trial.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6
Scott Grimes, 6137377700 ext. 70523, sgrimes@ohri.ca
About this study
Official title: A Phase II Study of the Use of MRI-defined Focal Boosts With Stereotactic Body Radiotherapy for Localized Prostate Cancer
External beam radiotherapy combined with androgen deprivation therapy is a standard treatment option for localized prostate cancer. The current standard involves delivering radiotherapy uniformly throughout the prostate gland in daily fractions, five days per week, for approximately four weeks. In this study, radiotherapy will be delivered using an ultra-hypofractionated approach in three larger fractions on alternating days over one week Multiparametric magnetic resonance imaging will be used to guide focal dose escalation to parts of the gland harboring tumor, which could potentially reduce the risk of cancer recurrence compared to standard dose of radiotherapy. The aim of this study is to confirm that this approach can be delivered safely, that is, with rates of urinary and bowel side effects at 1 year of follow-up that are not significantly greater than the current standard.
Read the detailed description
External beam radiotherapy (RT) in combination with androgen deprivation therapy (ADT) is a standard definitive treatment for localized prostate cancer. It confers long-term oncologic outcomes equivalent to those of radical prostatectomy. The current standard approach for prostate RT consists of uniform irradiation of the entire gland. This technique employs computed tomography (CT) images for planning, in which disease is not readily apparent. Multiparametric magnetic resonance imaging (mpMRI) of the prostate allows for accurate visualization of clinically significant tumour foci within the prostate gland. It thereby permits selective escalation of dose to tumours within the gland - a so-called focal boost or "microboost" - with the aim of improving treatment efficacy.
The current standard approach to prostate RT involves delivery of treatment in daily fractions, five days per week, over four weeks. Prostate cancer appears to exhibit an uncommon fractionation sensitivity among solid tumours. A consequence of this is that hypofractionation - that is, delivery of RT with larger fraction sizes - may further improve the therapeutic ratio. A number of large-scale studies have shown promise for an ultra-hypofractionated approach (that is, larger than 5-Gy fractions) in the treatment of localized prostate cancer.
There is an unmet need for innovations in radiotherapy that further reduce the risk of relapse without increasing toxicity or compromising health-related quality of life and that reduce the treatment burden. Both focal intraprostatic boosts - informed by mpMRI findings - and ultra-hypofractionation represent promising approaches to achieve this objective. To date, the optimal regimen that combines these two innovations remains to be explored. In this trial, we will investigate in a single-arm prospective cohort the safety of an mpMRI-defined focal boost technique with a convenient and radiobiologically compelling ultra-hypofractionated radiotherapy regimen (consisting of three fractionas delivered over one week) for localized unfavourable intermediate and high-risk localized prostate cancer.
This is a single-arm prospective trial conducted in patients with unfavourable intermediate-risk or high-risk localized prostate cancer. Treatment consists of ultra-hypofractionated intensity-modulated, image-guided prostate radiotherapy delivered to 27 Gy in 3 fractions (1 fraction per day every other day, over a 5 day period) to uninvolved regions, with up to 39 Gy in 3 fractions delivered to mpMRI-defined intraprostatic lesions, assuming normal tissue dosimetric criteria can be safely met. Radiotherapy will be combined with concurrent/adjuvant androgen deprivation therapy (6 months duration in patients with intermediate-risk disease and 24 months for patients with high-risk disease). There will be follow-up assessments for toxicity, quality of life, and biochemical control. The primary endpoint will be prevalence of grade ≥ 2 genitourinary or gastrointestinal toxicity at 12 months.
Primary Objective The primary objective is to determine whether, in a population of men with unfavourable intermediate-risk or high-risk localized prostate cancer receiving a combination of three-fraction ultra-hypofractionated RT and adjuvant androgen deprivation therapy, an mpMRI-defined focal boost can be delivered with acceptable GU and GI toxicity at 1 year of follow-up.
Secondary Objectives
The secondary objectives are to evaluate, in a population of men with unfavourable intermediate-risk or high-risk localized prostate cancer, the effects of an mpMRI-defined focal boost on:
- Health-related quality of life
- Biochemical disease-free survival
- Conditions
- Prostatic Neoplasms
- Being tested
- Prostate SBRT with Focal Boost, Triptorelin Injection
- Keywords
- Localized Prostate Cancer, Intermediate Risk, High Risk, Stereotactic Body Radiotherapy, External Beam Radiotherapy, Hypofractionation, Focal Boost, Microboost, Androgen Deprivation Therapy, Multiparametric magnetic resonance imaging
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prostate SBRT with Focal BoostRadiation
Also called Ultrahypofractionated prostate radiotherapy with integrated microboost
Prostate stereotactic body radiotherapy delivered to 27 Gy in 3 fractions on alternating days to uninvolved regions with up to 39 Gy in 3 fractions delivered to mpMRI-defined intraprostatic lesions
Triptorelin InjectionDrug
Also called Androgen Deprivation Therapy
Six months of androgen deprivation therapy for intermediate-risk localized prostate cancer and 24 months for high-risk localized prostate cancer
| Study group | Role | What they receive |
|---|---|---|
| Prostate SBRT with Focal Boost and Androgen Deprivation Therapy | Experimental | Stereotactic body radiotherapy to 27 Gy in 3 fractions to uninvolved regions of the prostate glad and up to 39 Gy in 3 fractions to mpMRI-defined intraprostatic lesions, with concurrent/adjuvant androgen deprivation therapy (6 months for intermediate risk, 24 months for high risk) Receives: Radiation: Prostate SBRT with Focal Boost; Drug: Triptorelin Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genitourinary and gastrointestinal toxicity
Number of patients with grade 2 or greater genitourinary or gastrointestinal toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE ) version 5.0 and Radiation Therapy Oncology Group radiation toxicity scale
Measured: Up to 2 years
Secondary outcomes (2)
Bowel and urinary quality of life
Measured by Expanded Prostate Cancer Index Composite (EPIC)-26 bowel and urinary domains
Measured: Up to 2 years
Disease-free survival
Number of patients free of biochemical recurrence (defined according to the Phoenix definition as an increase in serum PSA that is ≥ 2 ng/mL above the nadir value observed following radiotherapy) or death from any cause
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2023
- Study start23 Nov 2023
- Primary completionJun 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prostate radiotherapy of 27 Gy in 3 fractions to uninvolved regions, up to 39 Gy in 3 fractions to mpMRI-defined intraprostatic lesions, with concurrent/adjuvant androgen deprivation therapy (6 months intermediate risk, 24 months for high risk)
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Knight Therapeutics (USA) Inc
- Responsible party
- Sponsor
- Investigators
- Scott C Morgan, MD, MSc, Principal investigator, The Ottawa Hospital Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05851547
- Sponsor's protocol ID
- 20220698-01H
- Acronym
- DEFINE
- Status last verified
- Jan 2024
- First submitted
- 21 Mar 2023
- Last updated
- 5 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Use of MRI-defined Focal Boosts With Stereotactic Body Radiotherapy for Localized Prostate Cancer
- ClinicalTrials.gov ID
- NCT05851547
- Acronym / sponsor ID
- DEFINE / 20220698-01H
- Conditions
- Prostatic Neoplasms
- Keywords
- Localized Prostate Cancer, Intermediate Risk, High Risk, Stereotactic Body Radiotherapy, External Beam Radiotherapy, Hypofractionation, Focal Boost, Microboost
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Knight Therapeutics (USA) Inc
- Study start
- 23 Nov 2023 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 9 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
External beam radiotherapy combined with androgen deprivation therapy is a standard treatment option for localized prostate cancer. The current standard involves delivering radiotherapy uniformly throughout the prostate gland in daily fractions, five days per week, for approximately four weeks. In this study, radiotherapy will be delivered using an ultra-hypofractionated approach in three larger fractions on alternating days over one week Multiparametric magnetic resonance imaging will be used to guide focal dose escalation to parts of the gland harboring tumor, which could potentially reduce the risk of cancer recurrence compared to standard dose of radiotherapy. The aim of this study is to confirm that this approach can be delivered safely, that is, with rates of urinary and bowel side effects at 1 year of follow-up that are not significantly greater than the current standard.
Detailed description
External beam radiotherapy (RT) in combination with androgen deprivation therapy (ADT) is a standard definitive treatment for localized prostate cancer. It confers long-term oncologic outcomes equivalent to those of radical prostatectomy. The current standard approach for prostate RT consists of uniform irradiation of the entire gland. This technique employs computed tomography (CT) images for planning, in which disease is not readily apparent. Multiparametric magnetic resonance imaging (mpMRI) of the prostate allows for accurate visualization of clinically significant tumour foci within the prostate gland. It thereby permits selective escalation of dose to tumours within the gland - a so-called focal boost or "microboost" - with the aim of improving treatment efficacy.
The current standard approach to prostate RT involves delivery of treatment in daily fractions, five days per week, over four weeks. Prostate cancer appears to exhibit an uncommon fractionation sensitivity among solid tumours. A consequence of this is that hypofractionation - that is, delivery of RT with larger fraction sizes - may further improve the therapeutic ratio. A number of large-scale studies have shown promise for an ultra-hypofractionated approach (that is, larger than 5-Gy fractions) in the treatment of localized prostate cancer.
There is an unmet need for innovations in radiotherapy that further reduce the risk of relapse without increasing toxicity or compromising health-related quality of life and that reduce the treatment burden. Both focal intraprostatic boosts - informed by mpMRI findings - and ultra-hypofractionation represent promising approaches to achieve this objective. To date, the optimal regimen that combines these two innovations remains to be explored. In this trial, we will investigate in a single-arm prospective cohort the safety of an mpMRI-defined focal boost technique with a convenient and radiobiologically compelling ultra-hypofractionated radiotherapy regimen (consisting of three fractionas delivered over one week) for localized unfavourable intermediate and high-risk localized prostate cancer.
This is a single-arm prospective trial conducted in patients with unfavourable intermediate-risk or high-risk localized prostate cancer. Treatment consists of ultra-hypofractionated intensity-modulated, image-guided prostate radiotherapy delivered to 27 Gy in 3 fractions (1 fraction per day every other day, over a 5 day period) to uninvolved regions, with up to 39 Gy in 3 fractions delivered to mpMRI-defined intraprostatic lesions, assuming normal tissue dosimetric criteria can be safely met. Radiotherapy will be combined with concurrent/adjuvant androgen deprivation therapy (6 months duration in patients with intermediate-risk disease and 24 months for patients with high-risk disease). There will be follow-up assessments for toxicity, quality of life, and biochemical control. The primary endpoint will be prevalence of grade ≥ 2 genitourinary or gastrointestinal toxicity at 12 months.
Primary Objective The primary objective is to determine whether, in a population of men with unfavourable intermediate-risk or high-risk localized prostate cancer receiving a combination of three-fraction ultra-hypofractionated RT and adjuvant androgen deprivation therapy, an mpMRI-defined focal boost can be delivered with acceptable GU and GI toxicity at 1 year of follow-up.
Secondary Objectives
The secondary objectives are to evaluate, in a population of men with unfavourable intermediate-risk or high-risk localized prostate cancer, the effects of an mpMRI-defined focal boost on:
- Health-related quality of life
- Biochemical disease-free survival
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prostate radiotherapy of 27 Gy in 3 fractions to uninvolved regions, up to 39 Gy in 3 fractions to mpMRI-defined intraprostatic lesions, with concurrent/adjuvant androgen deprivation therapy (6 months intermediate risk, 24 months for high risk)
| Arm | Type | Receives |
|---|---|---|
| Prostate SBRT with Focal Boost and Androgen Deprivation Therapy | Experimental | Radiation: Prostate SBRT with Focal Boost, Drug: Triptorelin InjectionStereotactic body radiotherapy to 27 Gy in 3 fractions to uninvolved regions of the prostate glad and up to 39 Gy in 3 fractions to mpMRI-defined intraprostatic lesions, with concurrent/adjuvant androgen deprivation therapy (6 months for intermediate risk, 24 months for high risk) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically confirmed adenocarcinoma of the prostate
- Unfavourable intermediate-risk or high-risk localized disease
- Unfavourable intermediate-risk prostate cancer is defined as intermediate-risk prostate cancer [that is, no high-risk features and one or more intermediate-risk factors: T2b-T2c, Gleason 3+4 (grade group 2) or Gleason 4+3 (grade group 3), or PSA 10-20 μg/L] and one or more of the following: 2 or 3 intermediate-risk factors; Gleason 4+3 (grade group 3); ≥ 50% biopsy cores positive
- High-risk localized prostate cancer is defined as at least one of the following: T3a-T3b; Gleason ≥ 8 (grade group 4 or grade group 5); PSA > 20 μg/L
- 3 Tesla prostate MRI done no more than 12 months prior to enrollment
Key exclusion criteria (11 listed)
- Evidence of pelvic nodal metastases or distant metastases (AJCC Stage T1-4 N1 M0-1 or T1-4 N0 M1 disease)
- Discordance between pre-enrollment prostate MRI and prostate biopsy findings, defined as biopsy cores with Gleason Gleason ≥ 4+3 (grade group ≥ 3) adenocarcinoma with no corresponding tumour focus seen on MRI
- Androgen deprivation therapy commenced more than 60 days prior to enrollment
- Intention to electively treat the pelvic lymph nodes with radiotherapy
- Other active malignancy within the previous three years (except adequately treated nonmelanomatous carcinoma of the skin or low-grade superficial bladder carcinoma)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prostate SBRT with Focal BoostAlso: Ultrahypofractionated prostate radiotherapy with integrated microboostProstate stereotactic body radiotherapy delivered to 27 Gy in 3 fractions on alternating days to uninvolved regions with up to 39 Gy in 3 fractions delivered to mpMRI-defined intraprostatic lesions | Radiation | Prostate SBRT with Focal Boost and Androgen Deprivation Therapy |
| Triptorelin InjectionAlso: Androgen Deprivation TherapySix months of androgen deprivation therapy for intermediate-risk localized prostate cancer and 24 months for high-risk localized prostate cancer | Drug | Prostate SBRT with Focal Boost and Androgen Deprivation Therapy |
Primary outcome
Genitourinary and gastrointestinal toxicity
Time frame: Up to 2 years
Number of patients with grade 2 or greater genitourinary or gastrointestinal toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE ) version 5.0 and Radiation Therapy Oncology Group radiation toxicity scale
2 secondary outcomes
Bowel and urinary quality of life
Time frame: Up to 2 years
Disease-free survival
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Scott C Morgan, MD, MSc principal investigator
The Ottawa Hospital Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Prostate SBRT with Focal Boost and Triptorelin Injection in people with Prostatic Neoplasms, run by Ottawa Hospital Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Scott Grimes (613-737-7700 ext. 70523, sgrimes@ohri.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genitourinary and gastrointestinal toxicity (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2024.