Prostate Margin Reduction to Reduce Acute Rectal Toxicity (PROTRACT)

Prostate Cancer Clinical Trial

— PROTRACT  

Official title:

Reducing Acute Rectal Toxicity for Hypofractionated Prostate Radiotherapy - An Multi-institution Pilot Study of Reduced PTV Margin

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04004858
• Other study ID #: 043-1819
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 1, 2019
• Est. completion date: August 1, 2021

Study information

• Verified date: July 2019
• Source: Southlake Regional Health Centre
• Contact: Charles Cho, MD
• Phone: 905-895-4521
• Email: ccho[@]southlakeregional.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objectives of this study are:

1. Retrospectively validate a reduced margin schema for intermediate risk prostate hypofractionated VMAT treatments

2. Demonstrate in a prospective pilot clinical trial that patients planned and treated with the reduced margin schema will have reduced acute rectal toxicity

Description:

Hypofractionated radiotherapy is being adopted as standard practice for intermediate risk prostate cancer patients. The objective of this project is to retrospectively validate whether reducing the Planning Target Volume (PTV), a margin placed around the prostate to account for movement and variability in patient placement, will have reduced acute rectal toxicity. The project will focus on patients with intermediate risk prostate cancer treated with hypofractionated Volumetric Modulated Arc Therapy (VMAT) from multiple institutions. The investigators intend to prospectively demonstrate that patients planned and treated with the reduced margin, along with using advanced image-guidance and consistent bladder and rectum preparation will have reduced acute rectal toxicity.

The project consists of two phases: phase one is a retrospective planning study and phase two is a prospective pilot clinical trial.

Phase one aims to validate the benefits of the proposed decrease in PTV margin by assessing whether the investigators can continue to deliver the intended radiation dose to the prostate while further sparing the rectum. This will be accomplished by evaluating the daily delivered dose on Cone-Beam Computed Tomography (CBCT), a daily scan performed during treatment that determines the location of the prostate and rectum. Using these CBCT scans, the investigators can reconstruct the radiation dose delivered to any organs of interest which was affected by their relative positions each day. There are two parts in this phase one retrospective planning study. Part one will focus on 30 intermediate risk prostate cancer cases already treated with hypofractionation (60 Gy in 20 fractions) using the standard PTV margins from all three participating institutions. All 30 cases will then be re-planned using the reduced PTV margin and dose reconstruction will be performed on daily CBCT to confirm adequate target coverage of the prostate. Part two aims to demonstrate that the reduced PTV margin can help enable hypofractionation. Thirty cases that were originally intended to receive a hypofractionated regimen of 60 Gy in 20 fractions but had to either switch to a standard fractionation treatment of 78 Gy in 39 fractions (a regimen used when 60Gy in 20 fractions is not achievable), or where there had to be compromised target coverage of the prostate, due to Organs at Risk (OAR) receiving unacceptable doses of radiation, will be selected. These cases will be re-planned with the validated smaller PTV margin to illustrate that they would now be eligible to receive hypofractionation due to the reduced dose to OARs.

Phase two aims to demonstrate that patients treated with the reduced PTV margin will have reduced acute rectal toxicity as evaluated by the Cancer Care Ontario (CCO) Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) Quality of Life (QOL) questionnaire. Two groups of patients will be accrued: one group of 25 patients will be planned and treated with the current standard PTV margin as the control group, while the second group of 25 patients will be planned and treated with the reduced PTV margin validated from the phase one retrospective study. A comparison of rectal toxicity scores between these two groups will then be carried out using the EPIC-CP questionnaire.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: August 1, 2021
• Est. primary completion date: August 1, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male patients with intermediate-risk prostate cancer receiving external beam radiotherapy

2. Age greater than or equal to 18 years

3. Agreeable to proposed follow-up schedule and able to complete quality of life questionnaire as proposed

Exclusion Criteria:

1. Previous radiotherapy to the pelvic region

2. Inflammatory bowel disease or chronic colitis.

3. Connective tissue disorders such as scleroderma.

4. Patients with hip replacements

Related Conditions & MeSH terms

• Prostate Cancer

Intervention

Radiation:
• External beam radiation therapy
Patient will receive 60Gy in 20 fractions as per standard practice

Locations

Country	Name	City	State
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Southlake Regional Health Centre	Sunnybrook Health Sciences Centre, University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (17)

Alayed Y et al: Clinical impact of reducing planning target volume margins during radiation therapy for localized prostate cancer: early outcomes of a 2-stage prospective trial. Int J Radiat Oncol Biol Phys 93:(S)E249, 2015

Battista JJ, Johnson C, Turnbull D, Kempe J, Bzdusek K, Van Dyk J, Bauman G. Dosimetric and radiobiological consequences of computed tomography-guided adaptive strategies for intensity modulated radiation therapy of the prostate. Int J Radiat Oncol Biol Phys. 2013 Dec 1;87(5):874-80. doi: 10.1016/j.ijrobp.2013.07.006. Epub 2013 Aug 24. — View Citation

Catton 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. — View Citation

Chang P, Szymanski KM, Dunn RL, Chipman JJ, Litwin MS, Nguyen PL, Sweeney CJ, Cook R, Wagner AA, DeWolf WC, Bubley GJ, Funches R, Aronovitz JA, Wei JT, Sanda MG. Expanded prostate cancer index composite for clinical practice: development and validation of a practical health related quality of life instrument for use in the routine clinical care of patients with prostate cancer. J Urol. 2011 Sep;186(3):865-72. doi: 10.1016/j.juro.2011.04.085. Epub 2011 Jul 23. — View Citation

Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, Graham J, Kirkbride P, Logue J, Malik Z, Money-Kyrle J, O'Sullivan JM, Panades M, Parker C, Patterson H, Scrase C, Staffurth J, Stockdale A, Tremlett J, Bidmead M, Mayles H, Naismith O, South C, Gao A, Cruickshank C, Hassan S, Pugh J, Griffin C, Hall E; CHHiP Investigators. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol. 2016 Aug;17(8):1047-1060. doi: 10.1016/S1470-2045(16)30102-4. Epub 2016 Jun 20. Erratum in: Lancet Oncol. 2016 Aug;17 (8):e321. — View Citation

Dearnaley DP, Khoo VS, Norman AR, Meyer L, Nahum A, Tait D, Yarnold J, Horwich A. Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial. Lancet. 1999 Jan 23;353(9149):267-72. — View Citation

Engels B, Soete G, Gevaert T, Storme G, Michielsen D, De Ridder M. Impact of planning target volume margins and rectal distention on biochemical failure in image-guided radiotherapy of prostate cancer. Radiother Oncol. 2014 Apr;111(1):106-9. doi: 10.1016/j.radonc.2014.02.009. Epub 2014 Mar 13. — View Citation

Gill SK, Reddy K, Campbell N, Chen C, Pearson D. Determination of optimal PTV margin for patients receiving CBCT-guided prostate IMRT: comparative analysis based on CBCT dose calculation with four different margins. J Appl Clin Med Phys. 2015 Nov 8;16(6):252–262. doi: 10.1120/jacmp.v16i6.5691. — View Citation

Howell D et al: Feasibility of implementing EPIC-CP: recommendations to enhance the quality of person-centred clinical care of men with early-stage prostate cancer. Cancer Care Ontario report.

Korzeniowski M, Kalyvas M, Mahmud A, Shenfield C, Tong C, Zaza K, Howell D, Brundage M. Piloting prostate cancer patient-reported outcomesin clinical practice. Support Care Cancer. 2016 May;24(5):1983-1990. doi: 10.1007/s00520-015-2949-5. Epub 2015 Oct 24. — View Citation

Lee WR et al: RTOG 0415: A phase III randomized study of hypofractionated 3DCRT/IMRT versus conventionally fractionated 3DCRT/IMRT in patients treated for favorable-risk prostate cancer.

National Comprehensive Cancer Network: Prostate cancer, 2016. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

Nijkamp J, Pos FJ, Nuver TT, de Jong R, Remeijer P, Sonke JJ, Lebesque JV. Adaptive radiotherapy for prostate cancer using kilovoltage cone-beam computed tomography: first clinical results. Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):75-82. Epub 2007 Sep 17. — View Citation

Nuver TT, Hoogeman MS, Remeijer P, van Herk M, Lebesque JV. An adaptive off-line procedure for radiotherapy of prostate cancer. Int J Radiat Oncol Biol Phys. 2007 Apr 1;67(5):1559-67. Epub 2007 Feb 15. — View Citation

Quon HC et al: PATRIOT trial: randomized phase II study of prostate stereotactic body radiotherapy comparing 11 versus 29 days overall treatment time. J Clin Oncol 33:(S)6-6, 2015.

Wei JT, Dunn RL, Litwin MS, Sandler HM, Sanda MG. Development and validation of the expanded prostate cancer index composite (EPIC) for comprehensive assessment of health-related quality of life in men with prostate cancer. Urology. 2000 Dec 20;56(6):899-905. — View Citation

Wortel RC, Incrocci L, Pos FJ, van der Heide UA, Lebesque JV, Aluwini S, Witte MG, Heemsbergen WD. Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts. Int J Radiat Oncol Biol Phys. 2016 Jun 1;95(2):680-9. doi: 10.1016/j.ijrobp.2016.01.031. Epub 2016 Jan 22. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduced acute rectal toxicity from reduced PTV margin	Patients planned and treated with reduced PTV margin will have a change of 2 points in Cancer Care Ontario (CCO) Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) bowel symptom scores, demonstrating better toxicity outcomes. This patient reported outcome questionnaire evaluates bowel symptom scores in four aspects: rectal pain or urgency of bowel movement, increased frequency of bowel movements, overall problems with bowel movements, and bloody stools. Each aspect has a score ranging from 0 to 4. The total scores for an individual patient ranges from 0 to 16, with lower score indicating a better outcome.	6 months