Stereotactic Ablative Radiotherapy (SABR) for Low Risk Prostate Cancer With Injectable Rectal Spacer

Phase II Study of Stereotactic Ablative Radiotherapy (SABR) for Low Risk Prostate Cancer With Injectable Rectal Spacer

The purpose is to determine if use of rectal spacers are effective at improving protection of rectum from high dose radiation, using rate of rectal ulceration as a surrogate measure of acute effects. It is also to determine whether it provides sufficient dosimetric benefits to warrant further clinical investigation in future SABR (Stereotactic Ablative Body Radiation) related clinical studies.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Device: Injectable Rectal Spacer (SpaceOAR, Duraseal or equivalent)

Detailed Description

A phase II study to assess safety and efficacy of the spacer injection process, ability of the spacer to effectively provide the space necessary to reduce acute events in the rectum, and also meet the SABR based rectal constraints, and to monitor stability of this process during SABR. Unlike IMRT, which uses smaller dose/fraction, when using such high dose/fraction, even a few mm of shift in spacer positioning may impact the dose that the rectum receives, and therefore, a rigorous study of stability of material during the SABR treatments will need to be determined. If there is some shift, by doing this study, we may be able to determine the margin of error that will be necessary in considering rectal organ dosimetry, based on the possible shift in positiong that may occur with the spacer over time.

As the SABR therapy is strictly local, we will select for patients with prostate cancer locally confined to the prostate gland. As such, we will select eligibility criteria of low risk patients to minimize risk of extraprostatic spread, seminal vesicle invasion, and nodal spread. Hormonal therapy may also be used to shrink prostates that are massively enlarged as this may also help further reduce length of rectum that will be irradiated. As the primary toxicity will likely be mucosal damage, we will avoid enrolling patients with pre-existing mucosal dysfunction (including those with previous radiation, TURP, very large prostate glands, inflammatory bowel disease) and immunosuppressed individuals based on our phase I experience[13]. In this way, patients will be uniformly selected in a fashion that would identify patients likely to receive benefit from the therapy.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• All patients must be willing and capable to provide informed consent to participate in the protocol.
• Eligible patients must have appropriate staging studies identifying them as AJCC stage T1 (a, b, or c) or T2a or T2b adenocarcinoma of the prostate gland. The patient should not have direct evidence of regional or distant metastases after appropriate staging studies. Histologic confirmation of cancer will be required by biopsy performed within 180 days of registration.
• The patient's Zubrod performance status must be 0-2.
• The Gleason score should be less than or equal to 6 or 3+4 if < 50% of a 12 core biopsy was involved.
• The serum PSA should be less than or equal to 10 ng/ml.
• Study entry PSA must not be obtained during the following time frames: 10 day period following prostate biopsy; following initiation of ADT; within 30 days after discontinuation of finasteride; or within 90 days after discontinuation of dutasteride.
• Age ≥ 18 years.
• Patients may have used prior hormonal therapy, but it should be limited to no more than 9 months of therapy prior to enrollment.
• The ultrasound, or CT based volume estimation of the patient's prostate gland should be ≤ 60 grams.

Exclusion Criteria:

• Subjects who have had previous pelvic radiotherapy or have had chemotherapy or surgery for prostate cancer.
• Subjects who have plans to receive other concomitant or post treatment adjuvant antineoplastic therapy while on this protocol including surgery, cryotherapy, conventionally fractionated radiotherapy, hormonal therapy, or chemotherapy given as part of the treatment of prostate cancer.
• Subjects who have undergone previous transurethral resection of the prostate (TURP) or cryotherapy to the prostate. Subjects who have significant urinary obstructive symptoms; AUA score must be ≤15 (alpha blockers allowed).
• Subjects who have a history of significant psychiatric illness.
• Men of reproductive potential who do not agree that they or their partner will use an effective contraceptive method such as condom/diaphragm and spermacidal foam, intrauterine device (IUD), or prescription birth control pills.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are all permissible).

• Severe, active co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months.
  • Transmural myocardial infarction within the last 6 months.
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration.
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.
  • Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.
  • Patients with history of inflammatory colitis (including Crohn's Disease and Ulcerative colitis) are not eligible.
• Subjects with a known allergy to polyethylene glycol hydrogel (spacer material) or contraindication to spacer products (Duraseal or SpaceOAR).
• Subjects with evidence of extraprostatic extension (T3a) or seminal vesicle involvement (T3b) on clinical evaluation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: No Arm; Study did not have Arm(s)	Device: Injectable Rectal Spacer (SpaceOAR, Duraseal or equivalent); Injectable Rectal Spacer (SpaceOAR, Duraseal or equivalent PEG based product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Reduction in Acute Per-prostatic Rectal Ulcer Events Events From 90%+ to <70% (Particularly in the Anterior Rectum)	The effectiveness of rectal spacer use was measured to determine if they are effective at improving protection of rectum from high dose radiation, using rate of rectal ulceration as a surrogate measure of acute effects	Median 9 months within the end of radiation treatment
Effectiveness of Space Creation of >= 7.5 mm in Protecting Rectum From Toxicity	The effectiveness of rectal spacer use was measured to determine if they are effective at improving protection of rectum from high dose radiation, using rate of rectal ulceration as a surrogate measure of acute effects	Median 9 months within the end of radiation treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Spacer Related Acute Toxicity	Assess spacer related acute toxicity. Spacer related toxicity could be related to the procedure itself (bleeding, infection, pain), or secondary effects of spacer (erectile dysfunction, persistent pain and discomfort). Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE V4.0) and version number 4.0 specified in the protocol. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event.	270 days
Determine Spacer's Ability to Change Percent Rectal Circumference (PRC) Receiving 39 Gy	Determine spacer's ability to change percent rectal circumference (PRC) receiving 39 Gy by at least 50%. This will be determined by using CT planning studies for dosimetric analysis before and after spacer placement.	1 month
Determine Spacer's Ability to Change Percent Rectal Circumference (PRC) Receiving 24 Gy.	Determine spacer's ability to change percent rectal circumference (PRC) receiving 24 and 39 Gy by at least 50%. This will be determined by using CT planning studies for dosimetric analysis before and after spacer placement.	1 month
Acute (Within 270 Days of Treatment) SABR-related Gastrointestinal (GI) Toxicities	Acute gastrointestinal (GI) toxicity is defined as grade 1-5 toxicity occurring prior to 270 days from the start of protocol treatment. It is graded based on CTCAE v4.0.	270 days
Acute (Within 270 Days of Treatment) SABR-related Genitourinary (GU) Toxicities	Acute genitourinary (GU)toxicity is defined as grade 1-5 toxicity occurring prior to 270 days from the start of protocol treatment. It is graded based on CTCAE v4.0.	270 days
Chronic (>270 Days From Treatment) SABR-related Genitourinary (GU) Toxicities	Delayed genitourinary (GU) toxicity is defined as grade 1-5 toxicity occurring after 270 days from the start of protocol treatment. It is graded based on CTCAE v4.0. Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE V4.0) and version number 4.0 specified in the protocol. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event.	From day 271 up to 540 days
Chronic (>270 Days From Treatment) SABR-related Gastrointestinal (GI) Toxicities	Delayed gastrointestinal (GI) toxicity is defined as grade 1-5 toxicity occurring after 270 days from the start of protocol treatment. It is graded based on CTCAE v4.0. Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE V4.0) and version number 4.0 specified in the protocol. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event.	From day 271 up to 540 days
Acute Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity- Irritative	Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0.	270 days
Acute Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity-Obstructive	Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0.	270 days
Acute Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity-Reproductive.	Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0.	270 days
Chronic Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity-Obstructive.	Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE V4.0) and version number 4.0 specified in the protocol. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event.	From day 271 up to 540 days
Chronic Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity-Reproductive.	Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE V4.0) and version number 4.0 specified in the protocol. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event.	From day 271 up to 540 days
Chronic Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity-Irritative.	Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE V4.0) and version number 4.0 specified in the protocol. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life threatening; Grade 4: Life threatening consequences; Grade 5: Death related to the adverse event.	From day 271 up to 540 days
Freedom From Biochemical Recurrence	Biochemical failure RTOG-ASTRO definition (also known as Phoenix definition) - Thus, when the PSA rises by more than 2 ng/ml above the lowest level (nadir) achieved after treatment, biochemical failure has occurred and the date of the failure is recorded at the time the nadir plus 2 ng/ml level is reached	4 year
Overall Survival	Overall survival as measured by percentage of participants who survived at 5 years. The survival time will be measured from the date of accession to the date of death.	5 year
Disease-specific Survival	Percentage of patients who did not die from prostate cancer at 5 years.	5 year
Local Relapse	Percentage of patients without local relapse at 3 years. Local relapse will be measured from the date of study entry to the date of documented local relapse as determined by clinical exam.	3 year
Regional Relapse	Percentage of patients without regional relapse at 3 years. Regional relapse will be measured from the date of study entry to the date of documented regional nodal recurrence or distant disease relapse.	3 years
Distant Relapse	Percentage of patients without distant relapse at 3 years. Distant relapse will be measured from the date of study entry to the date of documented regional nodal recurrence or distant disease relapse.	3 years
EPIC (Expanded Prostate Cancer Index Composite) Bowel Function	Outcomes for bowel function and effect on quality of life. Expanded Prostate Cancer Index Composite (EPIC) bowel function score (range, 0 (worst) -100 (best)). EPIC bowel urgency (percentages are for men reporting more than a small problem). EPIC bowel frequency (percentages are for men reporting more than a small problem). EPIC bowel leakage or fecal incontinence (percentages are for men having fecal incontinence at least once per week). EPIC bloody stools (percentages are for men having bloody stools half the time or more). EPIC bowel, pelvic, or rectal pain (percentages are for men reporting more than a small problem). EPIC bowel habits (percentages are for men reporting more than a small problem).	18 months
EPIC (Expanded Prostate Cancer Index Composite) Bowel Frequency	Outcomes for bowel function and effect on quality of life. Expanded Prostate Cancer Index Composite (EPIC) bowel function score (range, 0-100). EPIC bowel urgency (percentages are for men reporting more than a small problem). EPIC bowel frequency (percentages are for men reporting more than a small problem). EPIC bowel leakage or fecal incontinence (percentages are for men having fecal incontinence at least once per week). EPIC bloody stools (percentages are for men having bloody stools half the time or more). EPIC bowel, pelvic, or rectal pain (percentages are for men reporting more than a small problem). EPIC bowel habits (percentages are for men reporting more than a small problem).	18 months
EPIC (Expanded Prostate Cancer Index Composite) Bloody Stools	Outcomes for bowel function and effect on quality of life. Expanded Prostate Cancer Index Composite (EPIC) bowel function score (range, 0-100). EPIC bowel urgency (percentages are for men reporting more than a small problem). EPIC bowel frequency (percentages are for men reporting more than a small problem). EPIC bowel leakage or fecal incontinence (percentages are for men having fecal incontinence at least once per week). EPIC bloody stools (percentages are for men having bloody stools half the time or more). EPIC bowel, pelvic, or rectal pain (percentages are for men reporting more than a small problem). EPIC bowel habits (percentages are for men reporting more than a small problem).	18 months
EPIC (Expanded Prostate Cancer Index Composite) Bowel Habits	Outcomes for bowel function and effect on quality of life. Expanded Prostate Cancer Index Composite (EPIC) bowel function score (range, 0-100). EPIC bowel urgency (percentages are for men reporting more than a small problem). EPIC bowel frequency (percentages are for men reporting more than a small problem). EPIC bowel leakage or fecal incontinence (percentages are for men having fecal incontinence at least once per week). EPIC bloody stools (percentages are for men having bloody stools half the time or more). EPIC bowel, pelvic, or rectal pain (percentages are for men reporting more than a small problem). EPIC bowel habits (percentages are for men reporting more than a small problem).	18 months
EPIC (Expanded Prostate Cancer Index Composite) Bowel Urgency	Outcomes for bowel function and effect on quality of life. Expanded Prostate Cancer Index Composite (EPIC) bowel function score (range, 0-100). EPIC bowel urgency (percentages are for men reporting more than a small problem). EPIC bowel frequency (percentages are for men reporting more than a small problem). EPIC bowel leakage or fecal incontinence (percentages are for men having fecal incontinence at least once per week). EPIC bloody stools (percentages are for men having bloody stools half the time or more). EPIC bowel, pelvic, or rectal pain (percentages are for men reporting more than a small problem). EPIC bowel habits (percentages are for men reporting more than a small problem).	18 months
EPIC (Expanded Prostate Cancer Index Composite) Bowel Leakage/Fecal Incontinence	Outcomes for bowel function and effect on quality of life. Expanded Prostate Cancer Index Composite (EPIC) bowel function score (range, 0-100). EPIC bowel urgency (percentages are for men reporting more than a small problem). EPIC bowel frequency (percentages are for men reporting more than a small problem). EPIC bowel leakage or fecal incontinence (percentages are for men having fecal incontinence at least once per week). EPIC bloody stools (percentages are for men having bloody stools half the time or more). EPIC bowel, pelvic, or rectal pain (percentages are for men reporting more than a small problem). EPIC bowel habits (percentages are for men reporting more than a small problem).	18 months
EPIC (Expanded Prostate Cancer Index Composite) Bowel Pelvic/Rectal Pain	Outcomes for bowel function and effect on quality of life. Expanded Prostate Cancer Index Composite (EPIC) bowel function score (range, 0-100). EPIC bowel urgency (percentages are for men reporting more than a small problem). EPIC bowel frequency (percentages are for men reporting more than a small problem). EPIC bowel leakage or fecal incontinence (percentages are for men having fecal incontinence at least once per week). EPIC bloody stools (percentages are for men having bloody stools half the time or more). EPIC bowel, pelvic, or rectal pain (percentages are for men reporting more than a small problem). EPIC bowel habits (percentages are for men reporting more than a small problem).	18 months
EPIC (Expanded Prostate Cancer Index Composite) Urinary Function	Outcomes for urinary function and effect on quality of life. Expanded Prostate Cancer Index Composite (EPIC) urinary function score (range, 0 (worst)-100 (best)). EPIC urinary irritation or obstruction (range, 0-100).EPIC urinary incontinence (range, 0-100).	18 months
EPIC (Expanded Prostate Cancer Index Composite) Urinary Irritative/Obstructive	Outcomes for urinary function and effect on quality of life. Expanded Prostate Cancer Index Composite (EPIC) urinary function score (range, 0-100). EPIC urinary irritation or obstruction (range, 0 (worst)-100 (best)).EPIC urinary incontinence (range, 0-100).	18 months
EPIC (Expanded Prostate Cancer Index Composite) Urinary Incontinence	Outcomes for urinary function and effect on quality of life. Expanded Prostate Cancer Index Composite (EPIC) urinary function score (range, 0-100). EPIC urinary irritation or obstruction (range, 0-100).EPIC urinary incontinence (range, 0 (worst)-100 (best)).	18 months
AUA (American Urological Association) Quality of Life Questionnaire	AUA Questionnaire is used to measure urinary symptoms. AUA uses a 7-item self-report measure used to assess urinary urgency, frequency, and voiding symptoms. SYMPTOM SCORE: 0-7 (Mild) 8-19 (Moderate) 20-35 (Severe)	18 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Michael Folkert, MD, UT Southwestern Medical Center; Principal Investigator: Michael Zelefsky, MD, Memorial Sloan Kettering Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2014
• Primary Completion (Actual): January 29, 2018
• Study Completion (Actual): January 5, 2021

Study Registration Dates

• First Submitted: January 16, 2015
• First Submitted That Met QC Criteria: January 28, 2015
• First Posted (Estimate): February 3, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2022
• Last Update Submitted That Met QC Criteria: March 23, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: STU 092013-013