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

Primary Purpose

Colorectal Neoplasms

Status
Unknown status
Phase
Phase 3
Locations
Israel
Study Type
Interventional
Intervention
Propranolol and Etodolac
Sponsored by
Sheba Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Colorectal Neoplasms

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rabin- Beilinson Medical Center
  • Tel Aviv-Sourasky Medical Center
  • Sheba Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

1

2

Arm Description

Perioperative Propranolol and Etodolac

Placebo

Outcomes

Primary Outcome Measures

Rate of recurrent and metastatic cancer

Secondary Outcome Measures

magnitude and duration of surgically induced immune depression, as reflected in the blood samples
Early postoperative morbidity and mortality

Full Information

First Posted
April 26, 2009
Last Updated
July 10, 2011
Sponsor
Sheba Medical Center
Collaborators
Tel-Aviv Sourasky Medical Center, Rabin Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00888797
Brief Title
β-adrenergic Blocker and a COX2 Inhibitor for Prevention of Colorectal Cancer Recurrence
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2011
Overall Recruitment Status
Unknown status
Study Start Date
January 2010 (undefined)
Primary Completion Date
January 2017 (Anticipated)
Study Completion Date
January 2017 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Sheba Medical Center
Collaborators
Tel-Aviv Sourasky Medical Center, Rabin Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Perioperative Propranolol and Etodolac
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Propranolol and Etodolac
Intervention Description
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.
Primary Outcome Measure Information:
Title
Rate of recurrent and metastatic cancer
Time Frame
3 years
Secondary Outcome Measure Information:
Title
magnitude and duration of surgically induced immune depression, as reflected in the blood samples
Time Frame
early postoperative
Title
Early postoperative morbidity and mortality
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Oded Zmora, M.D.
Phone
972-3-5302247
Email
ozmora@post.post.tau.ac.il
Facility Information:
Facility Name
Rabin- Beilinson Medical Center
City
Petah Tikva
Country
Israel
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nir Wasserberg, M.D.
Email
nirw@clalit.org.il
First Name & Middle Initial & Last Name & Degree
Nir Wasserberg, M.D.
Facility Name
Tel Aviv-Sourasky Medical Center
City
Tal Aviv
Country
Israel
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hagit Tulchinsky, M.D.
Email
hagitt@tasmc.health.gov.il
First Name & Middle Initial & Last Name & Degree
Hagit Tulchinsky, M.D.
Facility Name
Sheba Medical Center
City
Tel Hashomer
ZIP/Postal Code
45858
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Oded Zmora, M.D.
Phone
972-3-5302247
Email
ozmora@post.tau.ac.il
First Name & Middle Initial & Last Name & Degree
Oded Zmora, M.D.
First Name & Middle Initial & Last Name & Degree
Marat Khaikin, M.D.

12. IPD Sharing Statement

Citations:
PubMed Identifier
24050955
Citation
Hicks BM, Murray LJ, Powe DG, Hughes CM, Cardwell CR. beta-Blocker usage and colorectal cancer mortality: a nested case-control study in the UK Clinical Practice Research Datalink cohort. Ann Oncol. 2013 Dec;24(12):3100-6. doi: 10.1093/annonc/mdt381. Epub 2013 Sep 19.
Results Reference
derived

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

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