PROSTATE CANCERSABR-DualNCT06027892
Two-fraction Versus Five-fraction Stereotactic Radiotherapy for Localized Prostate Cancer
A study testing Two-fraction stereotactic radiotherapy and Five-fraction stereotactic radiotherapy in people with PROSTATE CANCER, run by Rabin Medical Center at 1 site in Israel.
Trial summary
The goal of this clinical trial is to compare two dose schedules of stereotactic radiation therapy in patients with localized prostate cancer. Historically, external beam radiation to treat localized prostate cancer was given in small treatments over a period of multiple weeks. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- PROSTATE CANCER
- What is being tested?
- Two-fraction stereotactic radiotherapy and Five-fraction stereotactic radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 562 participants
- Where
- 1 siteIsrael
- Study dates
- 29 Dec 2022to Dec 2032
- Phase
- Interventional
- 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
- Male patients ≥18 years
- Diagnosis of low- or favorable intermediate-risk prostate adenocarcinoma
- T1-T2c
- Prostate specific antigen < 20
- Gleason 6 or 7 (3+4)
- Cannot had multiple intermediate-risk factors consistent with unfavorable intermediate risk disease
- Prostate gland < 60 cc (can include following cytoreductive androgen deprivation)
- International Prostate Symptom Score < 15 (unaided by a-adrenergic inhibitor or anticholinergic drugs)
Who cannot join
- Unfavorable intermediate-risk disease and above
- Chronic inflammatory bowel condition (IBD, Crohn's disease, Sarcoidosis, Rheumatic disease)
- Chronic immunosuppression
- Contraindications to hydrogel spacer placement
- Contraindications to a prostate MRI
- Any prior prostate cancer treatment
Show all 10Show fewer
- Prior pelvic radiotherapy
- Previous transurethral resection of the prostate (TURP) within 12 months
- Hip prosthesis
- Prior use of therapeutic androgen deprivation therapy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Assaf Moore, MD contact
Israel1 site, 1 recruiting
- Recruiting
Davidoff Cancer Center, Rabin Medical Center
Petah Tikva, Israel, 49100
Tal Shlezinger, 9148744461, talzda@clalit.org.il
About this study
Official title: Two-fraction Versus Five-fraction Stereotactic Radiotherapy for Localized Low- and Favorable Intermediate-risk Prostate Cancer: SABR-Dual
The goal of this clinical trial is to compare two dose schedules of stereotactic radiation therapy in patients with localized prostate cancer. Historically, external beam radiation to treat localized prostate cancer was given in small treatments over a period of multiple weeks. Recent studies have shown that with newer technologies and better understanding of how prostate cancer responds to radiation, the same effective dose can be given in as few as 5 treatments. This study is comparing this newer standard course of 5 treatments with an even shorter course of just 2 treatments. The dose for the 2 treatments is based on a form of internal radiation called brachytherapy, but in this study, that dose will be given using external radiation, without the need for invasive procedures.
In order to make sure that the radiation therapy is given in a way that minimizes the risk of side effects to the surrounding organs, including the rectum and bladder, prior to radiation a hydrogel material will be inserted behind the prostate in order to distance the rectum further from the prostate gland, and small gold markers will be inserted into the prostate to decrease any possible movement during treatment.
The main questions are whether 2-treatment radiation is tolerated as well and is as effective at treating prostate cancer, compared to the standard 5-treatment course of radiation.
Read the detailed description
Following publication of multiple prospective clinical trials demonstrating the biochemical progression free survival (bPFS) benefits of high dose radiation for the curative treatment of localized prostate cancer, typical external beam radiotherapy (EBRT) courses ranged from 38-45 daily fractions delivered over 7.5-9 weeks. Over the past two decades, monumental advances in EBRT have been achieved, allowing significant shortening of the standard radiotherapy course. With diagnostic, imaging, and technological developments, the ability to deliver higher doses per fraction further expanded and an improved radiobiologic understanding of the response of prostate adenocarcinoma revealed that ultrahypofractionated regimen could take advantage of the comparatively low a/b ratio of prostate cancer cells. As a result of these two streams of development, stereotactic ablative radiation therapy (SABR) emerged as an accepted standard of care for definitive treatment in the low- and favorable intermediate-risk settings.
At both the individual and systems levels, efficient delivery of patient care and prudent utilization of medical resources is at the forefront. Given the ubiquity of prostate cancer and high volumes of patients in treatment centers across the globe, there remains meaningful potential for substantial improvements in patient throughput and cost of care. Presently, the shortest treatment courses for low- and favorable intermediate-risk prostate cancer are radical prostatectomy and low-dose-rate (LDR) brachytherapy, which offer an excellent likelihood of cure but entail degrees of invasiveness that may not be appropriate, feasible, or desirable for all patients, and include additional costs associated with operating room facilities and anesthesia. Surgical patients typically require a brief inpatient hospital stay. A comparable radiation therapy treatment course could help address many of these concerns and offer effective and efficient patient care.
A strong and mature precedent for a two-fraction course of high dose radiation can be found in the realm of high-dose-rate (HDR) brachytherapy. Under anesthesia, a radioactive source is programmed to traverse catheters that have been transperineally inserted into the prostate in order to produce a desired dose deposit. bPFS rates range between 91%-97% in the modern literature. While attempts were made to deliver single-fraction HDR brachytherapy (typical dose of 19 Gy), trials resulted in inferior oncologic outcomes, and to date, standard HDR treatment courses are comprised of two-fraction definitive treatment or single-fraction combined with EBRT. Radiobiologically, based on the particularly low a/b of prostate cancer cells and unique cell cycling, there is suggestion that at least two fractions are necessary for complete tumor eradication.
There exists, to date, limited data on the safety and effectiveness of prostate SABR delivered in fewer than five fractions. A recent proof-of-concept study by Greco et al compared single-dose SABR of 24 Gy to 5 fractions of 9 Gy in favorable intermediate and unfavorable intermediate risk patients. The results demonstrated comparable four-year prostate specific antigen outcomes for favorable intermediate disease though inferior PFS for unfavorable intermediate disease. Objective and patient reported genitourinary and gastrointestinal toxicities were not significantly different, though one of the 15 patients in the single-fraction arm experienced delayed grade 3 urethral stenosis. Magli et al published acceptable 1-year toxicity outcomes for a novel three-fraction regimen of SABR for low- and favorable intermediate-risk patients, to a dose of 40 Gy. MRI based planning was utilized, gold fiducials and a hydrogel spacer were placed, and a catheter was inserted in the bladder for each fraction. They observed rates of 11.9% and 1.7% acute grade 2 and 3 urinary toxicity, respectively, and 8.5% acute grade 2 rectal toxicity, all of which resolved by 12 months. Alayed et al published safety and efficacy results of their prospective single-cohort study of low- and intermediate-risk patients undergoing a two-fraction SABR regimen to a dose of 26 Gy. On their sample of 30 patients, they reported no acute grade 3+ gastrointestinal or genitourinary toxicity, and one instance each in later follow up, comparable or even slightly better than that from five-fraction protocols.
Multiple questions remain regarding the potential role for and safety of delivering SABR in fewer than five fractions. These include optimal patient selection, ideal dose fractionation, proper techniques to assure necessary avoidance of surrounding normal tissue, and how to balance dose to organs at risk with the accepted requirement of a planning target volume (PTV) to account for inevitable setup uncertainty. Importantly, recent endoscopic reports reveal notably high rates of rectal ulceration after dose-escalated SABR, and placement of a hydrogel spacer has been demonstrated to significantly reduce this risk. Placement of a resorbable hydrogel spacer to displace the rectum away from the high dose region, allowing for a posterior safety margin to account for potential intra-fractional motion, instead of a rectal balloon, is essential for accomplishing rectal sparing while facilitating additional assurance regarding treatment accuracy.
In the context of modern dose escalation, and in lieu of a strong body of HDR-brachytherapy data supporting a two-fraction approach to ultra-high dose treatment with initial experiences of two-fraction SABR, direct comparison of a non-invasive and broadly generalizable two-fraction SABR regimen to the standard approach of five-fraction regimen is logical. Institutional studies have emerged in the recent years demonstrating evidence for safety of ultra-hypofractionated regimen in fewer than five fractions of SABR, and large-scale randomized data is much needed. Aided by the ability to achieve necessary rectal dose constraints through placement of a rectal hydrogel, this approach may serve as an appropriate balance between minimizing the number of treatments necessary while allowing for delivery of the higher dose needed to optimize likelihood of cure.
- Conditions
- PROSTATE CANCER
- Being tested
- Two-fraction stereotactic radiotherapy, Five-fraction stereotactic radiotherapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Two-fraction stereotactic radiotherapyRadiation
Definitive prostate radiotherapy will be delivered to a dose biologically comparable to 40 Gy in 5 treatments, but in only 2 treatments
Five-fraction stereotactic radiotherapyRadiation
Definitive prostate radiotherapy will be delivered to a standard stereotactic dose of 40 Gy in 5 treatments
| Study group | Role | What they receive |
|---|---|---|
| Two-fraction stereotactic radiotherapy | Experimental | Participants receive stereotactic ablative radiotherapy in two treatments to a dose of 27 Gy, with the options to boost a high-grade lesion to 30 Gy Receives: Radiation: Two-fraction stereotactic radiotherapy |
| Five-fraction stereotactic radiotherapy | Active comparator | Participants receive stereotactic ablative radiotherapy in five treatments to a dose of 40 Gy, with the options to boost a high-grade lesion to 45 Gy Receives: Radiation: Five-fraction stereotactic radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biochemical Progression Free Survival
Phoenix definition
Measured: five-year
Secondary outcomes (7)
Freedom From Progression
biochemical failure, clinical failure, death from any cause
Measured: five-year
Distant metastasis free survival
Survival without development of distant metastatic disease
Measured: five-year
Prostate cancer specific survival
Survival with cause of death or censoring without residual or recurrent prostate cancer
Measured: five-year
Time to prostate specific antigen nadir (< 0.2) - Longitudinal response
Biochemical prostate specific antigen response over time
Measured: five-year
Time to salvage treatment
Time interval until need for salvage treatment for residual or recurrent disease
Measured: five-year
Physician-reported Genitourinary/Gastrointestinal toxicity
Toxicity caused by the intervention as graded by the physician
Measured: Every 3 months until 24 months
Patient-reported Genitourinary/Gastrointestinal toxicity
Toxicity caused by the intervention as graded by the patient
Measured: Every 3 months until 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2023
- Study start29 Dec 2022
- Primary completionDec 2027 (estimated)
- Study completionDec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for PROSTATE CANCERStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 562 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elisha T Fredman, MD, Principal investigator, Davidoff Cancer Center, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06027892
- Sponsor's protocol ID
- RMC-0199-22
- Other IDs
- MOH_2022-08-30_012007
- Acronym
- SABR-Dual
- Status last verified
- Aug 2024
- First submitted
- 31 Aug 2023
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data used in the results publication will be provided with participating researchers
Publications
Gharzai LA, Jiang R, Wallington D, Jones G, Birer S, Jairath N, Jaworski EM, McFarlane MR, Mahal BA, Nguyen PL, Sandler H, Morgan TM, Reichert ZR, Alumkal JJ, Mehra R, Kishan AU, Fizazi K, Halabi S, Schaeffer EM, Feng FY, Elliott D, Dess RT, Jackson WC, Schipper MJ, Spratt DE. Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis. Lancet Oncol. 2021 Mar;22(3):402-410. doi: 10.1016/S1470-2045(20)30730-0.
PubMed 33662287Abramowitz MC, Li T, Buyyounouski MK, Ross E, Uzzo RG, Pollack A, Horwitz EM. The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer. Cancer. 2008 Jan 1;112(1):55-60. doi: 10.1002/cncr.23139.
PubMed 17968996Marcello M, Denham JW, Kennedy A, Haworth A, Steigler A, Greer PB, Holloway LC, Dowling JA, Jameson MG, Roach D, Joseph DJ, Gulliford SL, Dearnaley DP, Sydes MR, Hall E, Ebert MA. Reduced Dose Posterior to Prostate Correlates With Increased PSA Progression in Voxel-Based Analysis of 3 Randomized Phase 3 Trials. Int J Radiat Oncol Biol Phys. 2020 Dec 1;108(5):1304-1318. doi: 10.1016/j.ijrobp.2020.07.030. Epub 2020 Jul 30.
PubMed 32739320Folkert MR, Zelefsky MJ, Hannan R, Desai NB, Lotan Y, Laine AM, Kim DWN, Neufeld SH, Hornberger B, Kollmeier MA, McBride S, Ahn C, Roehrborn C, Timmerman RD. A Multi-Institutional Phase 2 Trial of High-Dose SAbR for Prostate Cancer Using Rectal Spacer. Int J Radiat Oncol Biol Phys. 2021 Sep 1;111(1):101-109. doi: 10.1016/j.ijrobp.2021.03.025. Epub 2021 Mar 19.
PubMed 33753140Kim DW, Cho LC, Straka C, Christie A, Lotan Y, Pistenmaa D, Kavanagh BD, Nanda A, Kueplian P, Brindle J, Cooley S, Perkins A, Raben D, Xie XJ, Timmerman RD. Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of stereotactic body radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2014 Jul 1;89(3):509-17. doi: 10.1016/j.ijrobp.2014.03.012.
PubMed 24929162Alayed Y, Cheung P, Chu W, Chung H, Davidson M, Ravi A, Helou J, Zhang L, Mamedov A, Commisso A, Commisso K, Loblaw A. Two StereoTactic ablative radiotherapy treatments for localized prostate cancer (2STAR): Results from a prospective clinical trial. Radiother Oncol. 2019 Jun;135:86-90. doi: 10.1016/j.radonc.2019.03.002. Epub 2019 Mar 19.
PubMed 31015175Magli A, Farneti A, Faiella A, Ferriero M, Landoni V, Giannarelli D, Moretti E, de Paula U, Gomellini S, Sanguineti G. Toxicity at 1 Year After Stereotactic Body Radiation Therapy in 3 Fractions for Localized Prostate Cancer. Int J Radiat Oncol Biol Phys. 2021 Sep 1;111(1):93-100. doi: 10.1016/j.ijrobp.2021.03.027. Epub 2021 Mar 19.
PubMed 33745951Greco C, Pares O, Pimentel N, Louro V, Santiago I, Vieira S, Stroom J, Mateus D, Soares A, Marques J, Freitas E, Coelho G, Seixas M, Lopez-Beltran A, Fuks Z. Safety and Efficacy of Virtual Prostatectomy With Single-Dose Radiotherapy in Patients With Intermediate-Risk Prostate Cancer: Results From the PROSINT Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 May 1;7(5):700-708. doi: 10.1001/jamaoncol.2021.0039.
PubMed 33704378Morton G, McGuffin M, Chung HT, Tseng CL, Helou J, Ravi A, Cheung P, Szumacher E, Liu S, Chu W, Zhang L, Mamedov A, Loblaw A. Prostate high dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy. Radiother Oncol. 2020 May;146:90-96. doi: 10.1016/j.radonc.2020.02.009. Epub 2020 Mar 5.
PubMed 32146259Viani GA, Arruda CV, Assis Pellizzon AC, De Fendi LI. HDR brachytherapy as monotherapy for prostate cancer: A systematic review with meta-analysis. Brachytherapy. 2021 Mar-Apr;20(2):307-314. doi: 10.1016/j.brachy.2020.10.009. Epub 2021 Jan 15.
PubMed 33461894Pickles T, Morris WJ, Kattan MW, Yu C, Keyes M. Comparative 5-year outcomes of brachytherapy and surgery for prostate cancer. Brachytherapy. 2011 Jan-Feb;10(1):9-14. doi: 10.1016/j.brachy.2009.12.004.
PubMed 20605535Hoffman KE, Penson DF, Zhao Z, Huang LC, Conwill R, Laviana AA, Joyce DD, Luckenbaugh AN, Goodman M, Hamilton AS, Wu XC, Paddock LE, Stroup A, Cooperberg MR, Hashibe M, O'Neil BB, Kaplan SH, Greenfield S, Koyama T, Barocas DA. Patient-Reported Outcomes Through 5 Years for Active Surveillance, Surgery, Brachytherapy, or External Beam Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer. JAMA. 2020 Jan 14;323(2):149-163. doi: 10.1001/jama.2019.20675.
PubMed 31935027Jackson WC, Silva J, Hartman HE, Dess RT, Kishan AU, Beeler WH, Gharzai LA, Jaworski EM, Mehra R, Hearn JWD, Morgan TM, Salami SS, Cooperberg MR, Mahal BA, Soni PD, Kaffenberger S, Nguyen PL, Desai N, Feng FY, Zumsteg ZS, Spratt DE. Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Systematic Review and Meta-Analysis of Over 6,000 Patients Treated On Prospective Studies. Int J Radiat Oncol Biol Phys. 2019 Jul 15;104(4):778-789. doi: 10.1016/j.ijrobp.2019.03.051. Epub 2019 Apr 6.
PubMed 30959121Lee WR, Dignam JJ, Amin MB, Bruner DW, Low D, Swanson GP, Shah AB, D'Souza DP, Michalski JM, Dayes IS, Seaward SA, Hall WA, Nguyen PL, Pisansky TM, Faria SL, Chen Y, Koontz BF, Paulus R, Sandler HM. Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer. J Clin Oncol. 2016 Jul 10;34(20):2325-32. doi: 10.1200/JCO.2016.67.0448. Epub 2016 Apr 4.
PubMed 27044935Catton CN, Lukka H, Gu CS, Martin JM, Supiot S, Chung PWM, Bauman GS, Bahary JP, Ahmed S, Cheung P, Tai KH, Wu JS, Parliament MB, Tsakiridis T, Corbett TB, Tang C, Dayes IS, Warde P, Craig TK, Julian JA, Levine MN. Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer. J Clin Oncol. 2017 Jun 10;35(17):1884-1890. doi: 10.1200/JCO.2016.71.7397. Epub 2017 Mar 15.
PubMed 28296582
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Two-fraction Versus Five-fraction Stereotactic Radiotherapy for Localized Low- and Favorable Intermediate-risk Prostate Cancer: SABR-Dual
- ClinicalTrials.gov ID
- NCT06027892
- Acronym / sponsor ID
- SABR-Dual / RMC-0199-22
- Conditions
- PROSTATE CANCER
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 562 participants (estimated)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Study start
- 29 Dec 2022 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2032 (estimated)
- First posted
- 7 Sep 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.
The goal of this clinical trial is to compare two dose schedules of stereotactic radiation therapy in patients with localized prostate cancer. Historically, external beam radiation to treat localized prostate cancer was given in small treatments over a period of multiple weeks. Recent studies have shown that with newer technologies and better understanding of how prostate cancer responds to radiation, the same effective dose can be given in as few as 5 treatments. This study is comparing this newer standard course of 5 treatments with an even shorter course of just 2 treatments. The dose for the 2 treatments is based on a form of internal radiation called brachytherapy, but in this study, that dose will be given using external radiation, without the need for invasive procedures.
In order to make sure that the radiation therapy is given in a way that minimizes the risk of side effects to the surrounding organs, including the rectum and bladder, prior to radiation a hydrogel material will be inserted behind the prostate in order to distance the rectum further from the prostate gland, and small gold markers will be inserted into the prostate to decrease any possible movement during treatment.
The main questions are whether 2-treatment radiation is tolerated as well and is as effective at treating prostate cancer, compared to the standard 5-treatment course of radiation.
Detailed description
Following publication of multiple prospective clinical trials demonstrating the biochemical progression free survival (bPFS) benefits of high dose radiation for the curative treatment of localized prostate cancer, typical external beam radiotherapy (EBRT) courses ranged from 38-45 daily fractions delivered over 7.5-9 weeks. Over the past two decades, monumental advances in EBRT have been achieved, allowing significant shortening of the standard radiotherapy course. With diagnostic, imaging, and technological developments, the ability to deliver higher doses per fraction further expanded and an improved radiobiologic understanding of the response of prostate adenocarcinoma revealed that ultrahypofractionated regimen could take advantage of the comparatively low a/b ratio of prostate cancer cells. As a result of these two streams of development, stereotactic ablative radiation therapy (SABR) emerged as an accepted standard of care for definitive treatment in the low- and favorable intermediate-risk settings.
At both the individual and systems levels, efficient delivery of patient care and prudent utilization of medical resources is at the forefront. Given the ubiquity of prostate cancer and high volumes of patients in treatment centers across the globe, there remains meaningful potential for substantial improvements in patient throughput and cost of care. Presently, the shortest treatment courses for low- and favorable intermediate-risk prostate cancer are radical prostatectomy and low-dose-rate (LDR) brachytherapy, which offer an excellent likelihood of cure but entail degrees of invasiveness that may not be appropriate, feasible, or desirable for all patients, and include additional costs associated with operating room facilities and anesthesia. Surgical patients typically require a brief inpatient hospital stay. A comparable radiation therapy treatment course could help address many of these concerns and offer effective and efficient patient care.
A strong and mature precedent for a two-fraction course of high dose radiation can be found in the realm of high-dose-rate (HDR) brachytherapy. Under anesthesia, a radioactive source is programmed to traverse catheters that have been transperineally inserted into the prostate in order to produce a desired dose deposit. bPFS rates range between 91%-97% in the modern literature. While attempts were made to deliver single-fraction HDR brachytherapy (typical dose of 19 Gy), trials resulted in inferior oncologic outcomes, and to date, standard HDR treatment courses are comprised of two-fraction definitive treatment or single-fraction combined with EBRT. Radiobiologically, based on the particularly low a/b of prostate cancer cells and unique cell cycling, there is suggestion that at least two fractions are necessary for complete tumor eradication.
There exists, to date, limited data on the safety and effectiveness of prostate SABR delivered in fewer than five fractions. A recent proof-of-concept study by Greco et al compared single-dose SABR of 24 Gy to 5 fractions of 9 Gy in favorable intermediate and unfavorable intermediate risk patients. The results demonstrated comparable four-year prostate specific antigen outcomes for favorable intermediate disease though inferior PFS for unfavorable intermediate disease. Objective and patient reported genitourinary and gastrointestinal toxicities were not significantly different, though one of the 15 patients in the single-fraction arm experienced delayed grade 3 urethral stenosis. Magli et al published acceptable 1-year toxicity outcomes for a novel three-fraction regimen of SABR for low- and favorable intermediate-risk patients, to a dose of 40 Gy. MRI based planning was utilized, gold fiducials and a hydrogel spacer were placed, and a catheter was inserted in the bladder for each fraction. They observed rates of 11.9% and 1.7% acute grade 2 and 3 urinary toxicity, respectively, and 8.5% acute grade 2 rectal toxicity, all of which resolved by 12 months. Alayed et al published safety and efficacy results of their prospective single-cohort study of low- and intermediate-risk patients undergoing a two-fraction SABR regimen to a dose of 26 Gy. On their sample of 30 patients, they reported no acute grade 3+ gastrointestinal or genitourinary toxicity, and one instance each in later follow up, comparable or even slightly better than that from five-fraction protocols.
Multiple questions remain regarding the potential role for and safety of delivering SABR in fewer than five fractions. These include optimal patient selection, ideal dose fractionation, proper techniques to assure necessary avoidance of surrounding normal tissue, and how to balance dose to organs at risk with the accepted requirement of a planning target volume (PTV) to account for inevitable setup uncertainty. Importantly, recent endoscopic reports reveal notably high rates of rectal ulceration after dose-escalated SABR, and placement of a hydrogel spacer has been demonstrated to significantly reduce this risk. Placement of a resorbable hydrogel spacer to displace the rectum away from the high dose region, allowing for a posterior safety margin to account for potential intra-fractional motion, instead of a rectal balloon, is essential for accomplishing rectal sparing while facilitating additional assurance regarding treatment accuracy.
In the context of modern dose escalation, and in lieu of a strong body of HDR-brachytherapy data supporting a two-fraction approach to ultra-high dose treatment with initial experiences of two-fraction SABR, direct comparison of a non-invasive and broadly generalizable two-fraction SABR regimen to the standard approach of five-fraction regimen is logical. Institutional studies have emerged in the recent years demonstrating evidence for safety of ultra-hypofractionated regimen in fewer than five fractions of SABR, and large-scale randomized data is much needed. Aided by the ability to achieve necessary rectal dose constraints through placement of a rectal hydrogel, this approach may serve as an appropriate balance between minimizing the number of treatments necessary while allowing for delivery of the higher dose needed to optimize likelihood of cure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Two-fraction stereotactic radiotherapy | Experimental | Radiation: Two-fraction stereotactic radiotherapyParticipants receive stereotactic ablative radiotherapy in two treatments to a dose of 27 Gy, with the options to boost a high-grade lesion to 30 Gy |
| Five-fraction stereotactic radiotherapy | Active comparator | Radiation: Five-fraction stereotactic radiotherapyParticipants receive stereotactic ablative radiotherapy in five treatments to a dose of 40 Gy, with the options to boost a high-grade lesion to 45 Gy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male patients ≥18 years
- Diagnosis of low- or favorable intermediate-risk prostate adenocarcinoma
- Prostate gland < 60 cc (can include following cytoreductive androgen deprivation)
- International Prostate Symptom Score < 15 (unaided by a-adrenergic inhibitor or anticholinergic drugs)
Key exclusion criteria (10 listed)
- Unfavorable intermediate-risk disease and above
- Chronic inflammatory bowel condition (IBD, Crohn's disease, Sarcoidosis, Rheumatic disease)
- Chronic immunosuppression
- Contraindications to hydrogel spacer placement
- Contraindications to a prostate MRI
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 |
|---|---|---|
| Two-fraction stereotactic radiotherapyDefinitive prostate radiotherapy will be delivered to a dose biologically comparable to 40 Gy in 5 treatments, but in only 2 treatments | Radiation | Two-fraction stereotactic radiotherapy |
| Five-fraction stereotactic radiotherapyDefinitive prostate radiotherapy will be delivered to a standard stereotactic dose of 40 Gy in 5 treatments | Radiation | Five-fraction stereotactic radiotherapy |
Primary outcome
Biochemical Progression Free Survival
Time frame: five-year
Phoenix definition
7 secondary outcomes
Freedom From Progression
Time frame: five-year
Distant metastasis free survival
Time frame: five-year
Prostate cancer specific survival
Time frame: five-year
Time to prostate specific antigen nadir (< 0.2) - Longitudinal response
Time frame: five-year
Time to salvage treatment
Time frame: five-year
Physician-reported Genitourinary/Gastrointestinal toxicity
Time frame: Every 3 months until 24 months
Patient-reported Genitourinary/Gastrointestinal toxicity
Time frame: Every 3 months until 24 months
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 15 Nov 2024.
- Background: PubMed 33662287Gharzai LA, Jiang R, Wallington D, Jones G, Birer S, Jairath N, Jaworski EM, McFarlane MR, Mahal BA, Nguyen PL, Sandler H, Morgan TM, Reichert ZR, Alumkal JJ, Mehra R, Kishan AU, Fizazi K, Halabi S, Schaeffer EM, Feng FY, Elliott D, Dess RT, Jackson WC, Schipper MJ, Spratt DE. Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis. Lancet Oncol. 2021 Mar;22(3):402-410. doi: 10.1016/S1470-2045(20)30730-0.
- Background: PubMed 17968996Abramowitz MC, Li T, Buyyounouski MK, Ross E, Uzzo RG, Pollack A, Horwitz EM. The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer. Cancer. 2008 Jan 1;112(1):55-60. doi: 10.1002/cncr.23139.
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- Individual participant dataSharing planned: Yes. All individual participant data used in the results publication will be provided with participating researchers
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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.
Assaf Moore, MD contact
Elisha T Fredman, MD principal investigator
Davidoff Cancer Center, Rabin Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Two-fraction stereotactic radiotherapy and Five-fraction stereotactic radiotherapy in people with PROSTATE CANCER, run by Rabin Medical Center at 1 site in Israel.
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 8 inclusion and 10 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 15 Nov 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 Israel. 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.
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 Elisha T Fredman, MD (9148744461, elishafre@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biochemical Progression Free Survival (time frame: five-year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06027892, which also lists 21 linked publications.
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 15 Nov 2024.