β-adrenergic Blocker and a COX2 Inhibitor for Prevention of Colorectal Cancer Recurrence

July 10, 2011 updated by: Sheba Medical Center

Perioperative β-adrenergic Blocker and a COX2 Inhibitor in Patients Undergoing Resection for Primary Colon and Rectal Cancer: Effect on Tumor Recurrence and Postoperative Immune Perturbations. A Multicenter Randomized Prospective Trial.

Colon and rectal cancer is the second most prevalent malignant disease in the western world, causing significant morbidity, mortality, and healthcare sources use. Treating colon and rectal cancer with curative intent generally includes resection of the primary tumor. Despite its crucial role, surgery by itself induce physiological changes resulting in significant immune depression and other physiological perturbations, which may in turn play a significant role in the initiation of new metastases and the progression of pre-existing dormant metastases. The aim of this study is to assess the use of perioperative medical intervention using a combination of a β-adrenergic blocker (Propranolol) and a COX2 inhibitor (Etodolac), in order to attenuate the surgically induced immunosuppression and other physiological perturbations, aiming to reduce the rate of tumor recurrence and distant metastatic disease.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Israel
      • Petah Tikva, Israel
        • Not yet recruiting
        • Rabin- Beilinson Medical Center
        • Contact:
        • Principal Investigator:
          • Nir Wasserberg, M.D.
      • Tal Aviv, Israel
        • Not yet recruiting
        • Tel Aviv-Sourasky Medical Center
        • Contact:
        • Principal Investigator:
          • Hagit Tulchinsky, M.D.
      • Tel Hashomer, Israel, 45858
        • Recruiting
        • Sheba Medical Center
        • Contact:
        • Principal Investigator:
          • Oded Zmora, M.D.
        • Sub-Investigator:
          • Marat Khaikin, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients planned for surgery for primary resection of colon and rectal cancer in curative intent.
  • Single colonic or rectal carcinoma, proofed by full colonoscopy and tumor biopsy. If colonoscopy failed to reach the cecum, proximal colonic investigation will be made using contract enema or CT colonography.
  • No evidence of metastatic disease prior to surgery. Minimal workup would include abdominal CT with IV contrast (or CT+liver US) and chest XR.
  • Age between 18 and 75 year old.
  • ASA score of 1-3
  • The patient is able to understand the study objectives and procedures, able to comply with the protocol, and is capable to sign an informed consent.

Exclusion Criteria:

  • Patients with metastatic disease, known prior to surgery.
  • Patients in whom metastatic disease is found at surgery will complete the intervention phase, followed for additional month for potential complications, and will exit the study to allow potential participation in further clinical trials.
  • Patients in whom surgical resection is planned without curative intent.
  • Patients with renal failure, measured by Creatinine level >1.5
  • Patients with significant heart failure (NYH 3 or higher)
  • Patients with significant liver failure (known cirrhosis, Bilirubin level>2)
  • Patients suffering from asthma
  • Patients with known allergy to one or more of the study medications
  • Patients with known allergy to any medication from the non-steroidal anti-inflammatory drug group.
  • Patients with diabetes (type 1 or 2).
  • Patients treated chronically with one or more of the study medications
  • Patients treated chronically with any type of Beta adrenergic blocker.
  • Patients treated chronically with any type of COX inhibitor.
  • Patients with second or third degree AV block.
  • Patients with sinus bradycardia (patients with heart rate of less than 50).
  • Patients with sick sinus syndrome.
  • Patients with Prinzmetal's angina
  • Patients with right sided heart failure owing to pulmonary hypertension.
  • Patients with significant cardiomegaly
  • Patients with (current) pheochromocytoma
  • Patients with chronic Digoxin treatment
  • Patients with active peptic disease
  • Patients with peripheral vascular disease
  • Patients with history or concomitant malignant disease of any type.
  • Patients who were treated with chemotherapy in the last 10 years for any reason besides neo-adjuvant therapy for rectal cancer within the last six months.
  • Pregnant woman.
  • Patients participating in any other clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 2
Placebo
Drug: Propranolol and Etodolac
Both study medications will be given orally for an intervention phase of 20 days as follows: 5 days prior to surgery, on the day of surgery, and 14 days postoperatively. Etodolac:800 mg PO bid for the entire intervention period,Propranolol:20 mg PO bid for 5 preoperative days, 80 mg PO bid on the day of surgery, 40 mg PO bid for the first postoperative week, 20 mg PO bid for the second postoperative week.
Active Comparator: 1
Perioperative Propranolol and Etodolac
Drug: Propranolol and Etodolac
Both study medications will be given orally for an intervention phase of 20 days as follows: 5 days prior to surgery, on the day of surgery, and 14 days postoperatively. Etodolac:800 mg PO bid for the entire intervention period,Propranolol:20 mg PO bid for 5 preoperative days, 80 mg PO bid on the day of surgery, 40 mg PO bid for the first postoperative week, 20 mg PO bid for the second postoperative week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate of recurrent and metastatic cancer
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
magnitude and duration of surgically induced immune depression, as reflected in the blood samples
Time Frame: early postoperative
early postoperative
Early postoperative morbidity and mortality
Time Frame: 30 days
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sheba Medical Center

Collaborators

Rabin Medical Center
Tel-Aviv Sourasky Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Anticipated)

January 1, 2017

Study Completion (Anticipated)

January 1, 2017

Study Registration Dates

First Submitted

April 26, 2009

First Submitted That Met QC Criteria

April 27, 2009

First Posted (Estimate)

April 28, 2009

Study Record Updates

Last Update Posted (Estimate)

July 12, 2011

Last Update Submitted That Met QC Criteria

July 10, 2011

Last Verified

July 1, 2011

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHEBA-09-6994-OZ-CTIL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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