CivaSheet With Radical Prostatectomy & Adjuvant External Beam Radiation

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

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).

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Civasheet 60 Gy; Radiation: Adjuvant external beam radiation therapy; Radiation: Civasheet 75 Gy

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10019
      • Mount Sinai West

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group 1 of 60 Gy dose; 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; implantable proposed doses of Civasheet are 60 Gy; Radiation: Adjuvant external beam radiation therapy; 45 Gy in 25 fractions; Other Names: EBRT
Experimental: group 2 of 60 Gy dose; 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; implantable proposed doses of Civasheet are 60 Gy; Radiation: Adjuvant external beam radiation therapy; 45 Gy in 25 fractions; Other Names: EBRT
Experimental: group 1 of 75 Gy dose; 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: Adjuvant external beam radiation therapy; 45 Gy in 25 fractions; Other Names: EBRT; Radiation: Civasheet 75 Gy; implantable proposed doses of Civasheet are 75 Gy
Experimental: group 2 of 75 Gy dose; 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: Adjuvant external beam radiation therapy; 45 Gy in 25 fractions; Other Names: EBRT; Radiation: Civasheet 75 Gy; implantable proposed doses of Civasheet are 75 Gy

What is the study measuring?

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
Number of Surgical Complications	Number of surgical major complications (major complications defined as Clavien≥3.): intraoperative, post operative - acute (< 90 days) and late (18 months). Grade III - Requiring surgical, endoscopic or radiological intervention Grade IV - Life-threatening complication (including central nervous system (CNS) complications) requiring intensive care (IC/ICU)-management Grade V - Death of a patient	intraoperative, postoperative - acute (< 90 days) and late (18 months)
Number of Participants With Biochemical Recurrence (BCR)	Number of participants with Biochemical recurrence (BCR) at 6-month follow-up after EBRT. BCR was defined as a post-prostatectomy serum prostate-specific antigen (PSA) level greater than 0.2 nanograms per milliliter (ng/mL).	6-month follow-up after EBRT
Number of Participants With Erectile Dysfunction	Number of participants with Erectile Dysfunction at least 6 months after EBRT	6 months after EBRT
Number of Participants With PSA Persistence	Number of participants with PSA persistence which is defined as PSA persistently greater than 0.2 ng/mL after surgery.	40 months
Number of Participants With Urinary Incontinence	Number of Participants with Urinary Incontinence at least 6 months after EBRT	at least 6 months after EBRT, up to 40 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Acute Radiation Toxicity	Number of participants with Acute (occurring within 90 days) radiation toxicity using the Radiation Therapy Oncology Group (RTOG) Acute Toxicity Scale and Late Radiation Morbidity scales; including Grade 4-5 hematuria, fistula formation, proctitis or death.	3 months
Number of Participants With Late Radiation Toxicity	Number of participants with Late (occurring after 90 days) radiation toxicity using the Radiation Therapy Oncology Group (RTOG) Acute Toxicity Scale and Late Radiation Morbidity scales; including Grade 4-5 hematuria, fistula formation, proctitis or death.	after 90 days, up to 4 years 10 months
Number of Radiation Adverse Event(s)	National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0); 5 Grades where Grade 1 is the better outcome and Grade 5 is the worse outcome	4 years 10 months

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Ketan K. Badani, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2018
• Primary Completion (Actual): December 20, 2020
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: August 29, 2018
• First Posted (Actual): September 4, 2018

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: surgery; radiation therapy; brachytherapy; prostatectomy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: GCO 16-1314; PD 16-03067 (Other Identifier: Icahn School of Medicine at Mount Sinai)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The individual participant data (IPD) sharing plan will be based on sharing patient information on REDcap. REDcap is an electronic database that will be used to share the data with other researcher.
• IPD Sharing Time Frame: Duration of study
• IPD Sharing Access Criteria: Employed Mount Sinai Researchers
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes