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

NCT ID: NCT00994110

Last Updated: 2016-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 439 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2014-09-30

Brief 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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Pasireotide (SOM230)

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Allen, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24849084 (View on PubMed)

Related Links

http://www.mskcc.org

Memorial Sloan-Kettering Cancer Center

Other Identifiers

09-039

Identifier Type: -

Identifier Source: org_study_id