CivaSheet With Radical Prostatectomy & Adjuvant External Beam Radiation

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Civasheet 60 Gy
* Radiation: Civasheet 75 Gy
* Radiation: Adjuvant external beam radiation therapy


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 3+3 dose escalation study to determine MTD
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1 of 60 Gy dose<br>The first 3 subsequent patients with high risk prostate cancer will be undergoing radical prostatectomy Interventions: Civasheet 60 Gy + Adjuvant external beam radiation therapy | Radiation: Civasheet 60 Gy<br>* implantable proposed doses of Civasheet are 60 Gy<br>Radiation: Adjuvant external beam radiation therapy<br>* 45 Gy in 25 fractions<br>* Other names: EBRT;|
| Experimental: group 2 of 60 Gy dose<br>The second 3 subsequent patients with high risk prostate cancer will be undergoing radical prostatectomy Interventions: Civasheet 60 Gy + Adjuvant external beam radiation therapy | Radiation: Civasheet 60 Gy<br>* implantable proposed doses of Civasheet are 60 Gy<br>Radiation: Adjuvant external beam radiation therapy<br>* 45 Gy in 25 fractions<br>* Other names: EBRT;|
| Experimental: group 1 of 75 Gy dose<br>The third 3 subsequent patients with high risk prostate cancer will be undergoing radical prostatectomy Interventions: Civasheet 75 Gy + Adjuvant external beam radiation therapy | Radiation: Civasheet 75 Gy<br>* implantable proposed doses of Civasheet are 75 Gy<br>Radiation: Adjuvant external beam radiation therapy<br>* 45 Gy in 25 fractions<br>* Other names: EBRT;|
| Experimental: group 2 of 75 Gy dose<br>The fourth 3 subsequent patients with high risk prostate cancer will be undergoing radical prostatectomy Interventions: Civasheet 75 Gy + Adjuvant external beam radiation therapy | Radiation: Civasheet 75 Gy<br>* implantable proposed doses of Civasheet are 75 Gy<br>Radiation: Adjuvant external beam radiation therapy<br>* 45 Gy in 25 fractions<br>* Other names: EBRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerable Dose (MTD) | MTD is defined as the highest dose of the Civasheet® not yielding unacceptable toxicity. Specifically if > 33 % of subjects experience dose limiting toxicity (DLT) at any dose level, the dose level below that level will be considered the MTD. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical Complication Rate | Rate for surgical complications, acute (< 90 days) and late (18 months days) | 90 days | 
| Prostate Specific Antigen (PSA) | Serum PSA levels | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brachytherapy, prostatectomy, radiation therapy, surgery