Clinical trial NCT03147768: Laser Tissue Welding - Distal Pancreatectomy Sealing Study
Official title: Phase I Feasibility Trial To Study The Safety Of Sealing Resected Pancreatic Surfaces After Partial Distal Pancreatectomy Using Laser Tissue Welding
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Tumor, Benign
Pancreatic Neoplasms
Pancreatic Adenocarcinoma
Pancreatic Pseudocyst
Pancreatic Neuroendocrine Tumor
Pancreas; Insulinoma
Pancreatic Cyst
Pancreatic Teratoma
Pancreatic Polypeptide Tumor
Pancreatic Vipoma
Pancreatic Cystadenoma
Pancreas Injury
Pancreatic Gastrinoma
Pancreatic Glucagonoma
Keywords: Laser Tissue Welding
Pancreatic Sealing
Hemostasis
Pancreatic Tumors
Pancreatic Resection
Pancreatic leakage
LTW
Lead sponsor: Laser Tissue Welding, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
name: CHI St. Luke's Health, Texas
First posted: 2017-05-10
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open Label Combination Product (Laser + Biologic + Drug) regulated as a device
Primary purpose: DEVICE_FEASIBILITY

Brief summary: The laser tissue welding device is intended for use in patients requiring sealing of the pancreas after partial pancreatectomy, and including those patients who are fully heparinized or have hemodilutional coagulation failure.

The hypothesis is that the laser tissue welding device is safe and effective in sealing the pancreas, thereby decreasing the blood loss (operative and post-operative), and pancreatic juice leakage for patients when the Laser Tissue Welding device is used after pancreatic resection.

Detailed description: UNMET CLINICAL NEED

In the United States, pancreatic cancer is the fourth leading cause of cancer-related death in both men and women and will be the second leading case by 2030. Pancreatoduodenectomy (Whipple procedure) and distal partial pancreatectomy is used to treat pancreatic tumors, and these procedures are associated with a high rate of morbidity due to pancreatic fistulae.

As per the Surveillance, Epidemiology and End Results (SEER) Program: It is estimated that 41,609 men and women (21,370 men and 21,770 women) will be diagnosed with and 38,460 men and women will die of cancer of the pancreas in 2013. The five-year survival is dismal, 24.1% for localized malignancy, and drops to 6% if there is regional spread. There are 45,220 new cases in 2013 and 38,460 deaths.

Distal Pancreatectomy may be indicated for malignant exocrine tumors of the body and tail of pancreas (62%), insulinomas, chronic pancreatitis (12%), pancreatic pseudocysts, non pancreatic tumors (23%) and injury due to trauma.

Due to heighten awareness and preventative care, there has been an increase in detection of incidental small pancreatic mass cases due to widespread use of abdominal cross sectional imaging and thus an increase in the amount of pancreatic surgery performed. This is the stage when curative resections may be possible.

1. Surgical removal of the tumor is the only chance of a cure at T1A.
2. All pancreatic tumors at any stage require bulk reduction by a surgical procedure.

For patients undergoing distal pancreatectomy, pancreatic fistulas occurred post-operatively in 31% of patients. Over the long-term Kazanjian et al analyzed, 182 patients from 1996-2005 who underwent Pancreatoduodenectomy to treat ductal adenocarcinoma, concluded that the principal factor influencing long-term survival was operative blood loss. Pancreatic fistula is a main cause of postoperative morbidity, and is associated with numerous further complications, such as intra-abdominal abscesses, wound infection, sepsis, electrolyte imbalance, malabsorption, and hemorrhage, and with a dramatically increase in healthcare resource utilization.

The current state-of-art pancreatic surgical resections have an unacceptable pancreatic leak rate of 30-50%. This is because there are no FDA cleared or approved sealants or devices found to be safe or effective for sealing this organ. The current standard of care is anything but standard because of the use of off-label devices and sealants.

* Endo GIA Staplers: 510 (k) k111825 Cleared on basis of "literature review" without animal or human safety or efficacy data.
* Gore SeamGuard staple/suture reinforcement material 510 (k) k043056 Synthetic bio absorbable glycolide and trimethylene carbonate copolymer. Cleared on basis of in-vivo studies done "without performance standards" under section 514.
* Surgical Sealants: All used "off label": None are FDA cleared or approved for pancreatic surgery. These are Floseal, TachoSil, Tisseel, BioGlue, and CoSeal.

Jörg Kleeff et al reviewed the factors for surgical failure of distal pancreatectomy in 302 consecutive patients from 1993 to 2006 using four different surgical closures (gut anastomosis, seromuscular patch, suture and stapling device). Although distal pancreatectomy is less moribund as compared to Whipple procedure, morbidity was 32-52%, pancreatic fistulas occurred in 20-33% and mortality in 2% of cases. Pancreatic fistulas contributed significantly to morbidity, sepsis, length of stay and overall costs. Stapler closure of the pancreatic remnant is associated with a significantly higher fistula rate.

Laser Tissue Welding is the first combination (laser and biologic) class III surgical device intended to join and seal tissues accurately and instantly. The treatment process uses thermal energy created when a laser excites photosensitive dye molecules, to coagulate the protein albumin which transforms from a liquid to a solid instantly. Laser tissue welding creates a non-compressive, non-ablative sealing of tissues with microscopic thermal damage. This combination of a laser with albumin biologics stops bleeding and fluid leaks in nanoseconds without using sutures, hemostatic clotting factors (platelets/thrombin/fibrin), thermal or cryoablation.

Eligibility criteria: Inclusion Criteria:

Eligible participants will be 18 years and older of both genders.

1. T1a (≤ 4 cm, as measured by the maximal dimension by CT or MRI). Final determination of disease stage is made during the operation by the investigator. All resectable cystic, benign, primary or secondary malignant tumors.
2. Serum creatinine: ≤ 2.5 mg/dL
3. Glomerular filtration rate greater than ≥ 50 ml/min/m2
4. Platelet count ≥ 50,000/mm3
5. Prothrombin time \< 18 seconds
6. PTT not \>1.5 times control (except for therapeutically; anticoagulated nonrelated medical conditions \[e.g., atrial fibrillation\]);
7. Serum albumin levels \> 3g/dL (Normal range 3.5 to 5 g/dL)

Exclusion Criteria:

1. Age younger than 18 years' old
2. Severe uncorrected hypertension (\> 180 systolic and \>110 diastolic)
3. Uncorrectable coagulopathies (on Plavix, Aspirin or Lovanox)
4. Pregnancy
5. Females who are breast feeding who do not switch the infant to formula prior to surgery
6. Active urinary tract infection
7. T1b (\>4 cm) lesion and above
8. Systemic or local infection.
9. Subject has known allergy or intolerance to iodine or human serum albumin.
10. Recent febrile illness that precludes or delays participation preoperatively.
11. Treatment with another investigational drug or other intervention during the study and follow-up period.
12. Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study.

Primary outcomes:
measure: PRIMARY EFFICACY AS A SEALANT: Intra-operative blood loss
timeFrame: Intra-operative
Secondary outcomes:
measure: SECONDARY SAFETY: Post-operative blood loss requiring return to the operating room
timeFrame: 30 days
measure: SECONDARY SAFETY: Prolonged post-operative pancreatic leakage
timeFrame: 30 days
measure: SECONDARY SAFETY: Surgical space abscess
timeFrame: 30 days
Other outcomes:
measure: SECONDARY EFFICACY: Total operating time (minutes)
timeFrame: Intra-operative assessment
measure: SECONDARY EFFICACY: Pancreas clamp time (minutes)
timeFrame: Intra-operative assessment
measure: SECONDARY EFFICACY: Laser tissue welding time or time to hemostasis (Duration Metric)
timeFrame: Intra-operative assessment
measure: SECONDARY EFFICACY: Length of ICU stays (Duration and cost Metric )
timeFrame: 30 days
measure: SECONDARY EFFICACY: Total hospital stay (Duration and cost Metric )
timeFrame: 3 months
Locations:
city: Houston
country: United States
facility: Baylor CHI St. Luke's Medical Center
state: Texas
Study officials:
affiliation: Baylor CHI St. Luke's Medical Center, Houston, Texas
name: OMAR BARAKAT, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor CHI St. Luke's Medical Center, Houston, Texas
name: STEPHEN HAROLD, M.D.; MPH; CCRC
role: STUDY_DIRECTOR
References:
citation: Kleeff J, Diener MK, Z'graggen K, Hinz U, Wagner M, Bachmann J, Zehetner J, Muller MW, Friess H, Buchler MW. Distal pancreatectomy: risk factors for surgical failure in 302 consecutive cases. Ann Surg. 2007 Apr;245(4):573-82. doi: 10.1097/01.sla.0000251438.43135.fb.
citation: Goh BK. Re: Distal pancreatectomy: risk factors for surgical failure in 302 consecutive cases. Ann Surg. 2008 Feb;247(2):392-3; author reply 393. doi: 10.1097/SLA.0b013e318164022d. No abstract available.
citation: Kazanjian KK, Hines OJ, Duffy JP, Yoon DY, Cortina G, Reber HA. Improved survival following pancreaticoduodenectomy to treat adenocarcinoma of the pancreas: the influence of operative blood loss. Arch Surg. 2008 Dec;143(12):1166-71. doi: 10.1001/archsurg.143.12.1166.
citation: Shrikhande SV, D'Souza MA. Pancreatic fistula after pancreatectomy: evolving definitions, preventive strategies and modern management. World J Gastroenterol. 2008 Oct 14;14(38):5789-96. doi: 10.3748/wjg.14.5789.