Placebo Controlled Trial of SOM230 for the Reduction of Post-Pancreatectomy Fistula, Leak, and Abscess
Condition: Pancreatic Cancer
MeSH terms: Fistula
Intervention: Pasireotide (SOM230); placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Pasireotide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 439.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PANCREAS; Pasireotide; SOM230; saline placebo; 09-039

Summary:

      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.
    

Eligibility criteria:

        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.