AMNIOX CORD Study - Radical Prostatectomy With and Without Cryopreserved Umbilical Cord Allograft

• ClinicalTrials.gov Identifier: NCT04263025
• Recruitment Status: Recruiting
• First Posted: February 10, 2020
• Last Update Posted: December 19, 2023
• Sponsor: Hackensack Meridian Health
• Information provided by (Responsible Party): Hackensack Meridian Health

Tracking Information

• First Submitted Date: February 7, 2020
• First Posted Date: February 10, 2020
• Last Update Posted Date: December 19, 2023
• Actual Study Start Date: January 30, 2020
• Estimated Primary Completion Date: October 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2020)

• Erectile function [ Time Frame: At three months post surgery ]
  Erectile function will be evaluated using the International Index of Erectile Function (IIEF)
• Erectile function [ Time Frame: At six months post surgery ]
  Erectile function will be evaluated using the International Index of Erectile Function (IIEF)
• Erectile function [ Time Frame: At twelve months post surgery ]
  Erectile function will be evaluated using the International Index of Erectile Function (IIEF)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 15, 2022)

• Potency endpoint [ Time Frame: 6 weeks post op ]
  IIEF-6 Levels at 6 weeks post-op between the two treatment groups
• Potency endpoint [ Time Frame: 3 months post op ]
  IIEF-6 Levels at 3 months post-op between the two treatment groups
• Potency endpoint [ Time Frame: 6 months post op ]
  IIEF-6 Levels at 6 months post-op between the two treatment groups
• Potency endpoint [ Time Frame: 12 months post op ]
  IIEF-6 Levels at 12 months post-op between the two treatment groups
• Return to continence [ Time Frame: At 6 weeks post surgery ]
  Continence will be evaluated using the International Consultation of Incontinence Questionnaire - Short Form (ICIQ-SF)
• Return to continence [ Time Frame: At three months post surgery ]
  Continence will be evaluated using the International Consultation of Incontinence Questionnaire - Short Form (ICIQ-SF)
• Return to continence [ Time Frame: At six months post surgery ]
  Continence will be evaluated using the International Consultation of Incontinence Questionnaire - Short Form (ICIQ-SF)
• Return to continence [ Time Frame: At twelve months post surgery ]
  Continence will be evaluated using the International Consultation of Incontinence Questionnaire - Short Form (ICIQ-SF)
• Pad Weight [ Time Frame: 6 weeks post op ]
  Changes from baseline of average pad weight to 6 weeks post-op between treatment groups
• Pad Count [ Time Frame: 6 weeks post op ]
  Proportion of patients that wear 0 or 1 safety pads; 1-2 safety pads; and >2 safety pads per day
• Pad Weight [ Time Frame: 3 months post op ]
  Changes from baseline of average pad weight to 3 months post-op between treatment groups
• Pad Count [ Time Frame: 3 months post op ]
  Proportion of patients that wear 0 or 1 safety pads; 1-2 safety pads; and >2 safety pads per day
• Pad Weight [ Time Frame: 6 months post op ]
  Changes from baseline of average pad weight to 6 months post-op between treatment groups
• Pad Count [ Time Frame: 6 months post op ]
  Proportion of patients that wear 0 or 1 safety pads; 1-2 safety pads; and >2 safety pads per day
• Pad Weight [ Time Frame: 12 months post op ]
  Changes from baseline of average pad weight to 12 months post-op between treatment groups
• Pad Count [ Time Frame: 12 months post op ]
  Proportion of patients that wear 0 or 1 safety pads; 1-2 safety pads; and >2 safety pads per day
• Sexual encounter [ Time Frame: At three months post surgery ]
  Patients will be asked to complete the Sexual Encounter Profile (SEP) Diary to document after each sexual attempt
• Sexual encounter [ Time Frame: At six months post surgery ]
  Patients will be asked to complete the Sexual Encounter Profile (SEP) Diary to document after each sexual attempt
• Sexual encounter [ Time Frame: At twelve months post surgery ]
  Patients will be asked to complete the Sexual Encounter Profile (SEP) Diary to document after each sexual attempt
• Biochemical recurrence endpoint [ Time Frame: 6 weeks post-op ]
  Proportion of patients with biochemical recurrence at 6 weeks post-op between groups.
• Biochemical recurrence endpoint [ Time Frame: 3 months post-op ]
  Proportion of patients with biochemical recurrence at 3 months post-op between groups.
• Biochemical recurrence endpoint [ Time Frame: 6 months post-op ]
  Proportion of patients with biochemical recurrence at 6 months post-op between groups.
• Biochemical recurrence endpoint [ Time Frame: 12 months post-op ]
  Proportion of patients with biochemical recurrence at 12 months post-op between groups.
• Patient intercourse satisfaction endpoint [ Time Frame: 6 weeks post op ]
  Patient satisfaction using Likert score at 6 weeks post-op between groups
• Patient intercourse satisfaction endpoint [ Time Frame: 3 months post op ]
  Patient satisfaction using Likert score at 3 months post-op between groups
• Patient intercourse satisfaction endpoint [ Time Frame: 6 months post op ]
  Patient satisfaction using Likert score at 6 months post-op between groups
• Patient intercourse satisfaction endpoint [ Time Frame: 12 months post op ]
  Patient satisfaction using Likert score at 12 months post-op between groups
• Failure Events of Following RARP endpoint [ Time Frame: 2 weeks post-op ]
  Incidence of readmission for hospital stay at 2 weeks post-op between groups.
• Failure Events of Following RARP endpoint [ Time Frame: 2 weeks post-op ]
  Number of surgical interventions at 2 weeks post-op between groups

Original Secondary Outcome Measures (submitted: February 7, 2020)

• Return to continence [ Time Frame: At three months post surgery ]
  Continence will be evaluated using the International Consultation of Incontinence Questionnaire - Short Form (ICIQ-SF)
• Return to continence [ Time Frame: At six months post surgery ]
  Continence will be evaluated using the International Consultation of Incontinence Questionnaire - Short Form (ICIQ-SF)
• Return to continence [ Time Frame: At twelve months post surgery ]
  Continence will be evaluated using the International Consultation of Incontinence Questionnaire - Short Form (ICIQ-SF)
• Sexual encounter [ Time Frame: At three months post surgery ]
  Patients will be asked to complete the Sexual Encounter Profile (SEP) Diary to document after each sexual attempt
• Sexual encounter [ Time Frame: At six months post surgery ]
  Patients will be asked to complete the Sexual Encounter Profile (SEP) Diary to document after each sexual attempt
• Sexual encounter [ Time Frame: At twelve months post surgery ]
  Patients will be asked to complete the Sexual Encounter Profile (SEP) Diary to document after each sexual attempt

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: AMNIOX CORD Study - Radical Prostatectomy With and Without Cryopreserved Umbilical Cord Allograft
• Official Title: Prospective, Controlled Study Evaluating Recovery of Potency and Continence Following Robot-Assisted Radical Prostatectomy With and Without Cryopreserved Umbilical Cord Allograft
• Brief Summary: This study aims at evaluating if placement of CLARIX® CORD 1K during robotic prostatectomy decreases the time to achieve complete erectile and urinary function after the surgery. As part of the study, the patient will be asked to answer various questions after the surgery regarding sexual and urinary function.

Detailed Description

One hundred male patients who are scheduled for bilateral, nerve-sparing RARP that meet the eligibility criteria will be enrolled. These patients will be equally randomized (1:1) into two groups (n=50/group): one group will receive adjunctive CLARIX® CORD 1K (Amniox Medical, Inc., Miami, FL) during RARP, while the other group will undergo RARP without adjunctive CLARIX® CORD 1K. Subject stratification will be performed based on the surgeon that will be performing the RARP. All patients will be given the same routine preoperative, perioperative and postoperative evaluation and care aside from the CLARIX CORD 1K placement in the treatment group during RARP. RARP will be performed at Hackensack University Medical Center (30 Prospect Ave, Hackensack, NJ 07601) and follow up visits performed at Hackensack University Medical Group Urology (360 Essex Street, Suite 403, Hackensack, NJ 07601) or New Jersey Urology (255 W. Spring Valley Avenue Suite 101, Maywood, NJ 07607).

Two weeks prior to the RARP surgery, subjects are instructed to take low-dose oral phosphodiesterase type 5 inhibitors (i.e. 20 mg q.d. sildenafil citrate or 5 mg q.d. tadalafil) and perform standardized Kegel exercises (3x/day) which is our current standard care protocol. RARP surgery will be performed at Hackensack University Medical Center (Hackensack, NJ). The following are the key aspects of the RARP surgical technique which will be adhered to by all surgeons: 1) dissection of the bladder neck, seminal vesicles and vasa deferentia; 2) dissection of the neuroplexus from the posterior Denonvilliers' fascia and lateral prostatic fascia leaving the nerves intact; 3) division of the prostatic pedicles without cautery; 4) transection of the dorsal venous complex; and 5) urethrovesical anastomosis. More specifically, surgical technique includes exposing the prostate in the space of Retzius with the traditional anterior approach.

The prostatovesical tissue is dissected with monopolar electrocautery scissors with entry into the bladder proximal to the prostatovesical junction. The bladder neck is transected in the standard fashion followed by posterior dissection of the seminal vesicles and vasa deferentia.

Electrocautery is kept to a minimum when dissecting the seminal vesicles to avoid damage to the neuroplexus. (Note: each step hereafter must be performed by the PI or Sub-investigators, e.g. not a Resident Physician). A posterior surgical plane is then created between the rectum and prostate dorsally working from a medial to lateral direction and maintaining at least 1 layer of Denonvilliers' fascia on the rectal wall. The endopelvic fascia is then excised from lateral prostate and carried to capsule to create a plane of dissection immediately alongside the prostatic capsule and keeping the nerves attached laterally to the endopelvic fascia. Athermal division of each prostatic pedicle will be performed. Clips or suture may be placed on each pedicle at the discretion of the surgeon. The apex of the prostate is then dissected athermally sparing the neuroplexus. The dorsal vein complex is proximally transected with electrocautery while using the fourth arm to place traction on the prostate to define the space between the dorsal vein complex and the apex of the prostate. Apically, the prostate is divided from the urethra (paying special attention to the sphincter muscle and posterior lateral nerve bundle on each side) allowing the prostate to be removed. Once free, the prostate is placed in a collection bag and a drain is used for a certain period at the discretion of the surgeon.

Surgical site bleeding is managed using standard surgical techniques with sutures or cellulose polymer. If the patient is randomized to the treatment group, CLARIX CORD 1K is placed flat over the neuroplexis at the 5 and 7 clock position where the largest concentration of nerves exist. Sutures may be used to secure the CLARIX in place if necessary and cellulose polymer (Surgicel, Ethicon, Somerville, NJ) can be placed over the CLARIX CORD at the discretion of the physician.

At this point the bladder neck will be reconstructed as necessary to maintain a lumen of approximately 30 french. The vesicourethral anastomosis is performed using a V-lock barbed suture. The anastomosis will be tested by filling bladder to confirm the absence of leakage. If indicated, a bilateral pelvic lymph node dissection is performed (with clips at the discretion of the physician) using standard (borders along the external iliac artery and vein, obturator fossa, obturator nerve and pubic bone) or extended (borders additionally include internal iliac artery) technique at the discretion of the physician. Bleeding will be adequately managed. Postoperatively, all subjects are instructed to take low-dose oral phosphodiesterase type 5 inhibitors (i.e. 20 mg q.d. sildenafil citrate or 5 mg q.d. tadalafil) and perform standardized Kegel exercises (3x/day) following urethral catheter removal. When patients are sexually active, they may increase to full dosage of oral phosphodiesterase type 5 inhibitors up to twice a week. At 3 months after RARP, and if patients have severe or worse incontinence (defined as ICIQ score of >12) and desire additional treatment for urinary incontinence,[42] they will undergo pelvic floor therapy. Subjects will return for follow up visits at 6 weeks (±1 week), 3 months (±2 weeks), 6 months (±3 weeks) and 12 months (±4 weeks) when data will be collected.

Patient reported outcomes will be assessed including continence, potency, and satisfaction. Occurrence of adverse events, number of readmissions, and need for reintervention will also be recorded. Measurement of serum PSA levels will also be performed.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description:

Participant will be Blinded

Primary Purpose: Treatment

• Condition: Prostate Cancer

Intervention

• Biological: Cryopreserved Umbilical Cord Allograft
  CLARIX® CORD 1K (Amniox Medical, Miami, FL) is an umbilical cord allograft processed using the patented CRYOTEK™ process by TissueTech Inc. to devitalize all living cells but retain the natural structural and biological characteristics relevant to this tissue [43]. CLARIX® CORD 1K (6x3 cm in size) will be cut into two longitudinal pieces (1.5 cm in width) and placed circumferentially around each NVB as a nerve wrap during RARP. CLARIX® CORD 1K has been in market since 2013 in the United States as a "361 human cell and tissue-based product (HCT/P)" and is aseptically processed in compliance with current Good Tissue Practices (cGTP) as outlined in 21 CFR Part 1271.
• Procedure: Robot-Assisted Radical Prostatectomy
  Robot-Assisted Radical Prostatectomy (RARP) is the most common surgical technique used to treat clinically localized prostate cancer however robot-assisted radical prostatectomy

Study Arms

• Experimental: CLARIX CORD 1K
  They will receive adjunctive CLARIX® CORD 1K (Amniox Medical, Inc., Miami, FL) during Robot-Assisted Radical Prostatectomy (RARP).
  Interventions:

  • Biological: Cryopreserved Umbilical Cord Allograft
  • Procedure: Robot-Assisted Radical Prostatectomy
• Active Comparator: Controls
  They will undergo RARP without adjunctive CLARIX® CORD 1K.
  Intervention: Procedure: Robot-Assisted Radical Prostatectomy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 7, 2020): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 1, 2025
• Estimated Primary Completion Date: October 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male aged between 30 and 70 years old
2. Primary diagnosis of organ confined prostate cancer
3. Scheduled to undergo bilateral, nerve-sparing RARP
4. Patient has ICIQ-SF score <6
5. Patient has no erectile dysfunction (defined as IIEF-6 score ≥ 26)
6. Patient is willing to return for all visits as defined in the protocol
7. Patient is willing to follow the instruction of the Investigator
8. Patient has provided written informed consent

Exclusion Criteria:

1. Previous history of pelvic radiation
2. Previous history of simple prostatectomy or transurethral prostate surgery
3. Previous history of systemic therapy for prostate cancer
4. Patient has neurogenic bladder
5. Body weight less than 50 kg (110 pounds) or a body mass index greater than 40 kg/m2
6. History of open pelvic surgery within 5 years except for hernia repair
7. Scheduled at the time of screening to undergo chemotherapy, radiation, hormone therapy, or open surgery during the study period.
8. Any neurologic disorder or psychiatric disorder (e.g., Parkinson's Multiple Sclerosis, etc.) that might confound postsurgical assessments
9. Received administration of an investigational drug within 30 days prior to study, and/or has planned administration of another investigational product or procedure during participation in this study
10. Previous history of anaphylaxis or hypersensitivity to liposomal amphotericin- B

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Only male patients will be recruited as we are studying prostate cancer.

• Ages: 30 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sharon Seidman, RN; 5519963749; Sharon.Seidman@hmhn.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04263025
• Other Study ID Numbers: Pro2019-0452
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Hackensack Meridian Health
• Original Responsible Party: Same as current
• Current Study Sponsor: Hackensack Meridian Health
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michael Stifelman, MD; Chair of Urology Department

• PRS Account: Hackensack Meridian Health
• Verification Date: December 2023