Clinical trial NCT03657108: CivaSheet With Radical Prostatectomy & Adjuvant External Beam Radiation
Official title: A Phase I Single-Arm Open Label Dose-Escalation Study of CivaSheet With Radical Prostatectomy With or Without Adjuvant External Beam Radiation Therapy in Patients With High Risk Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Prostate Cancer
Keywords: brachytherapy
prostatectomy
radiation therapy
surgery
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2018-09-04
Enrollment: 6
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 dose escalation study to determine MTD
Primary purpose: TREATMENT

Brief summary: A phase I single-arm open label dose escalation study to evaluate the maximum tolerated dose (MTD) and safety of Civasheet® with radical prostatectomy (RP) and adjuvant external beam radiation therapy (EBRT) in a 3+3 dose escalation design among participants with high risk prostate cancer (PCa).

Detailed description: Using preoperative MRI imaging to identify areas suspicious of local advancement in addition to identifying areas with a higher likelihood of a positive margin during RP due to the presence of high risk features, Civasheet® and its inherently flexible structure allow the sheet to be directly implanted on areas suspicious for local advancement and positive surgical margins for direct application of radiation to these areas. The custom, single planar layer, integrative gold shielding of Civasheet® also allows radiation to be provided unidirectionally to allow healthy tissue (i.e., bladder, rectum) to be shielded from radiation; possibly affording a lower rate of gastrointestinal (GI) and genitourinary (GU) toxicity and adverse events. During EBRT, radiation especially for high risk PCa is provided at high rates to the entire prostatic bed with the seminal vesicles, pelvic lymph nodes and a surrounding margin often targeted to eliminate positive margins and cancer from locally advanced areas in which the cancer may have spread (i.e., seminal vesicles, bladder neck). These high rates of radiation often damage surrounding tissue and result in rectal and bladder complications in addition to urethral strictures among other adverse complications. Since Civasheet® will provide radiation to the prostatic bed, a lower dose of EBRT will be used to treat the prostatic bed and potentially lower adverse bladder and rectal effects compared to RP + RT at 60 Gy. 103 Pd seeds of Civasheet® also illuminate on imaging. Therefore placing Civasheet® based on pre-operative identification of areas suspicious for local advancement and areas of likely positive surgical margins during RP will allow for targeted EBRT to the locally advanced areas. Since EBRT can be targeted using Civasheet®, a lower and more direct dose of radiation during EBRT may be used to treat local advancement and positive surgical margins which will potentially reduce toxicity and complications associated with higher doses of radiation.

The above properties are likely to facilitate improved cancer control with more direct and local application of radiation to areas of local advancement surrounding the prostate. These features are also likely to facilitate a reduced complication and toxicity profile since Civasheet® allows EBRT to be applied more accurately and at a lower dose and also the unidirectional radiation applied directly by Civasheet® protects surrounding healthy tissue from receiving radiation.No other studies have attempted to use Civasheet® to improve PCa control and reduce toxicity and complications associated with radiation for participants with high-risk prostate cancer. The investigators anticipate that implanting Civasheet® on areas suspicious for local advancement and positive margins based on pre-operative MRI findings and identification of high risk features in addition to relying on the illumination provided by Civasheet® for targeted adjuvant EBRT will provide a safer complication profile and eventually provide evidence for superior cancer control, lower toxicity and less adverse events than EBRT+ RP alone in a future randomized controlled trial. The investigators therefore propose a phase I single-arm open label dose escalation study to evaluate the MTD and safety of Civasheet® with RP and adjuvant EBRT in a 3+3 dose escalation design among participants with high risk PCa.With this study, the investigators to better understand the MTD, safety and toxicity profile of Civasheet® in the setting of RP + adjuvant EBRT in the treatment of high-risk PCa.

Eligibility criteria: Inclusion Criteria:

* Any subject with National Comprehensive Cancer Network (NCCN) very high or high risk adenocarcinoma of the prostate defined as ≥T3a, Gleason score ≥ 8, or PSA \> 20 who is eligible for RP (open or robotic) with adjuvant EBRT as an initial treatment option.
* Any subject with NCCN Intermediate Risk adenocarcinoma of the prostate defined as T2b-T2c, Gleason score 7, or PSA 10-20 who is eligible for RP (open or robotic) with adjuvant EBRT as an initial treatment option and at least one of the following adverse features present in pre-operative imaging: seminal vesicle infiltration (SVI), extracapsular extension (ECE), N1 disease.
* Subject must have had a pre-operative MRI or must obtain a pre-operative MRI to be eligible for participation in this study.
* Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

* Any subject who has undergone prior radiation to the pelvis.
* Subjects presenting with distant metastases.
* On any investigational drug(s), androgen deprivation therapy or therapeutic device(s) within 30 days preceding screening.
* Currently taking immunosuppressants, or with poorly controlled diabetes (HbA1c \>8).

Primary outcomes:
measure: Maximum Tolerable Dose (MTD)
timeFrame: 90 days
Secondary outcomes:
measure: Number of Surgical Complications
timeFrame: intraoperative, postoperative - acute (< 90 days) and late (18 months)
measure: Number of Participants With Biochemical Recurrence (BCR)
timeFrame: 6-month follow-up after EBRT
measure: Number of Participants With Erectile Dysfunction
timeFrame: 6 months after EBRT
measure: Number of Participants With PSA Persistence
timeFrame: 40 months
measure: Number of Participants With Urinary Incontinence
timeFrame: at least 6 months after EBRT, up to 40 months
Other outcomes:
measure: Number of Participants With Acute Radiation Toxicity
timeFrame: 3 months
measure: Number of Participants With Late Radiation Toxicity
timeFrame: after 90 days, up to 4 years 10 months
measure: Number of Radiation Adverse Event(s)
timeFrame: 4 years 10 months
Locations:
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Ketan K. Badani, MD
role: PRINCIPAL_INVESTIGATOR
References: