Clinical trial NCT02353832: Stereotactic Ablative Radiotherapy (SABR) for Low Risk Prostate Cancer With Injectable Rectal Spacer
Official title: Phase II Study of Stereotactic Ablative Radiotherapy (SABR) for Low Risk Prostate Cancer With Injectable Rectal Spacer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2015-02-03
Enrollment: 44
Sex: MALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Reduction in Acute Per-prostatic Rectal Ulcer Events Events From 90%+ to <70% (Particularly in the Anterior Rectum)
timeFrame: Median 9 months within the end of radiation treatment
measure: Effectiveness of Space Creation of >= 7.5 mm in Protecting Rectum From Toxicity
timeFrame: Median 9 months within the end of radiation treatment
Secondary outcomes:
measure: Percentage of Participants With Spacer Related Acute Toxicity
timeFrame: 270 days
measure: Determine Spacer's Ability to Change Percent Rectal Circumference (PRC) Receiving 39 Gy
timeFrame: 1 month
measure: Determine Spacer's Ability to Change Percent Rectal Circumference (PRC) Receiving 24 Gy.
timeFrame: 1 month
measure: Acute (Within 270 Days of Treatment) SABR-related Gastrointestinal (GI) Toxicities
timeFrame: 270 days
measure: Acute (Within 270 Days of Treatment) SABR-related Genitourinary (GU) Toxicities
timeFrame: 270 days
measure: Chronic (>270 Days From Treatment) SABR-related Genitourinary (GU) Toxicities
timeFrame: From day 271 up to 540 days
measure: Chronic (>270 Days From Treatment) SABR-related Gastrointestinal (GI) Toxicities
timeFrame: From day 271 up to 540 days
measure: Acute Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity- Irritative
timeFrame: 270 days
measure: Acute Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity-Obstructive
timeFrame: 270 days
measure: Acute Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity-Reproductive.
timeFrame: 270 days
measure: Chronic Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity-Obstructive.
timeFrame: From day 271 up to 540 days
measure: Chronic Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity-Reproductive.
timeFrame: From day 271 up to 540 days
measure: Chronic Non-GI (Gastrointestinal) and Non-GU (Genitourinary) Toxicity-Irritative.
timeFrame: From day 271 up to 540 days
measure: Freedom From Biochemical Recurrence
timeFrame: 4 year
measure: Overall Survival
timeFrame: 5 year
measure: Disease-specific Survival
timeFrame: 5 year
measure: Local Relapse
timeFrame: 3 year
measure: Regional Relapse
timeFrame: 3 years
measure: Distant Relapse
timeFrame: 3 years
measure: EPIC (Expanded Prostate Cancer Index Composite) Bowel Function
timeFrame: 18 months
measure: EPIC (Expanded Prostate Cancer Index Composite) Bowel Frequency
timeFrame: 18 months
measure: EPIC (Expanded Prostate Cancer Index Composite) Bloody Stools
timeFrame: 18 months
measure: EPIC (Expanded Prostate Cancer Index Composite) Bowel Habits
timeFrame: 18 months
measure: EPIC (Expanded Prostate Cancer Index Composite) Bowel Urgency
timeFrame: 18 months
measure: EPIC (Expanded Prostate Cancer Index Composite) Bowel Leakage/Fecal Incontinence
timeFrame: 18 months
measure: EPIC (Expanded Prostate Cancer Index Composite) Bowel Pelvic/Rectal Pain
timeFrame: 18 months
measure: EPIC (Expanded Prostate Cancer Index Composite) Urinary Function
timeFrame: 18 months
measure: EPIC (Expanded Prostate Cancer Index Composite) Urinary Irritative/Obstructive
timeFrame: 18 months
measure: EPIC (Expanded Prostate Cancer Index Composite) Urinary Incontinence
timeFrame: 18 months
measure: AUA (American Urological Association) Quality of Life Questionnaire
timeFrame: 18 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Michael Folkert, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Centre
name: Michael Zelefsky, MD
role: PRINCIPAL_INVESTIGATOR
References: