Placebo Controlled Trial of SOM230 for the Reduction of Post-Pancreatectomy Fistula, Leak, and Abscess

Prospective Randomized, Double Blind, Placebo Controlled Trial of SOM230 for the Reduction of Post-Pancreatectomy Fistula, Leak, and Abscess

The purpose of this study is to help us learn more about how to lower the patient's risk of the most common complications after their pancreas operation. After tumors are removed and the remaining part of the pancreas is connected to the intestine or closed, a leakage of pancreatic fluid may occur. This fluid may form an "abscess" (collection of pus) or "fistula" that would need to be drained. A fistula is a persistent leakage of pancreatic fluid that sometimes occurs after pancreatic surgery. Fistulas, leaks, and abscesses are complications that are seen in roughly every 15-20 patients out of every 100 that have pancreas surgeries. Complications like these extend the patient's stay in the hospital after surgery. These complications may require the patient's doctor to perform additional tests or procedures to treat them.

The physical and emotional burden these complications place upon patients, as well as the financial cost to the health care system, can be great. The surgeons at Memorial Sloan-Kettering Cancer Center are conducting a study to determine if a drug, SOM230, can help reduce the rate of these complications. SOM230, also known as Pasireotide, is a drug that has been observed to reduce the rate of similar complications in other studies.

The surgeon would like to compare the effects, good and/or bad, of SOM230 with "placebo" (solution without medication) to see if SOM230 reduces the rate of fistulas, leaks and abscesses.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Pasireotide (SOM230); Other: placebo

• Study Type: Interventional
• Enrollment (Actual): 439
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female patients aged 18 years or greater.
• Signed informed consent
• Candidate for pancreaticoduodenectomy or distal pancreatectomy with or without splenectomy.

Exclusion Criteria:

• Pregnancy
• Patients with malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means.
• Patients with uncontrolled diabetes mellitus or a fasting plasma glucose > 250mg/dl.

Note: At the principle investigator's discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted.

• Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment.
• Patients who are at risk for QT prolongation. Risk factors include: patients with electrolyte disturbances such as hypokalemia, hypomagnesemia, and hypocalcemia; patients with a family history of long QT syndrome. syncope, and idiopathic sudden death; patients with concomitant diseases that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism, bradycardia, high-grade AV block, significant cardiac arrhythmias, or cardiac failure; patients using concomitant medications known to prolong the QT interval while receiving protocol treatment. These medications include selected antiarrhythmics, antihistamines, macrolide antibiotics, and /or tricyclic antidepressants as follows:

Albuterol Alfuzosin Amantadine Amiodarone Amitriptyline Amphetamine Arsenic Trioxide Astemizole Atazanavir Atomoxetine Azithromycin Chloroquine Clomipramine Dolasetron Metaproterenol Moxifloxacin Phenermine Phenylpropanolamine

• Those drugs not specifically listed above but possibly suspected of causing QT prolongation would not necessarily preclude patient registration, but would be discussed with the attending physician prior to initiation of protocol therapy.
• Patients with QTc >450 msec.
• Patients with liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
• Patients with acute cholecystitis
• Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (ELISA and Western blot).
• Patients with abnormal coagulation (INR>1.5) or patients receiving anticoagulants that affect PT (prothrombin time) or APTT ( activated thromboplastin time)
• Patients with WBC <3 K/mcL; PLT < 100 K/mcL
• Patients who have any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the Investigator.
• Patients who have participated in any clinical investigation with an investigational drug (other then pasireotide) within 30 days prior to dosing.
• Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR or s.c. formulations
• Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOM230; This is a randomized, double-blind, placebo controlled phase III trial of SOM230 vs. saline placebo in patients undergoing pancreaticoduodenectomy or distal pancreatectomy with or without splenectomy at Memorial Sloan-Kettering Cancer Center.	Drug: Pasireotide (SOM230); Patients will receive subcutaneous injection of SOM230 or placebo (NS, equivalent volume) on the day of operation prior to resection in the pre-surgical center. The initial subcutaneous injection of drug or placebo will be given at least one hour prior but no longer than 8 hours prior to transection of the pancreas. Patients will be continuously monitored in the OR following this dose administration, and both their cardiac and respiratory status will be closely followed. Postoperatively patients will receive study drug or placebo every 12 hours. Subcutaneous injections will continue until postoperative day 7, with the last dose administered in the evening on postoperative day 6, or until a pancreatic complication has been identified.
Placebo Comparator: placebo; This is a randomized, double-blind, placebo controlled phase III trial of SOM230 vs. saline placebo in patients undergoing pancreaticoduodenectomy or distal pancreatectomy with or without splenectomy at Memorial Sloan-Kettering Cancer Center.	Other: placebo; Patients will receive subcutaneous injection of SOM230 or placebo (NS, equivalent volume) on the day of operation prior to resection in the pre-surgical center. The initial subcutaneous injection of drug or placebo will be given at least one hour prior but no longer than 8 hours prior to transection of the pancreas. Patients will be continuously monitored in the OR following this dose administration, and both their cardiac and respiratory status will be closely followed. Postoperatively patients will receive study drug or placebo every 12 hours. Subcutaneous injections will continue until postoperative day 7, with the last dose administered in the evening on postoperative day 6, or until a pancreatic complication has been identified.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To Compare 60-day ≥Grade 3 Pancreatic Complication Rates (Fistula, Leak, and Abscess) as Defined by the MSKCC Surgical Secondary Events System Between Patients Who Receive Perioperative SOM230 and Saline Placebo.	60 days

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Peter Allen, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Allen PJ, Gonen M, Brennan MF, Bucknor AA, Robinson LM, Pappas MM, Carlucci KE, D'Angelica MI, DeMatteo RP, Kingham TP, Fong Y, Jarnagin WR. Pasireotide for postoperative pancreatic fistula. N Engl J Med. 2014 May 22;370(21):2014-22. doi: 10.1056/NEJMoa1313688. Erratum In: N Engl J Med. 2014 Jul 3; 371(1):94.

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: October 13, 2009
• First Submitted That Met QC Criteria: October 13, 2009
• First Posted (Estimate): October 14, 2009

Study Record Updates

• Last Update Posted (Estimate): February 1, 2016
• Last Update Submitted That Met QC Criteria: December 22, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: SOM230; Pasireotide; PANCREAS; saline placebo; 09-039
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Fistula; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pasireotide
• Other Study ID Numbers: 09-039