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

NCT00888797 | Unknown Phase 3

• 1 other identifier: SHEBA-09-6994-OZ-CTIL
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 3

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.

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Rate of recurrent and metastatic cancer

  3 years

Secondary Outcomes (2)

• magnitude and duration of surgically induced immune depression, as reflected in the blood samples

  early postoperative

• Early postoperative morbidity and mortality

  30 days

Study Arms (2)

1

ACTIVE COMPARATOR

Perioperative Propranolol and Etodolac

Drug: Propranolol and Etodolac

2

PLACEBO COMPARATOR

Placebo

Drug: Propranolol and Etodolac

Interventions

Propranolol and Etodolac DRUG

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.

1; 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Sheba Medical Center: lead
• Tel-Aviv Sourasky Medical Center: collaborator
• Rabin Medical Center: collaborator

Study Sites (3)

Rabin- Beilinson Medical Center

Petah Tikva, Israel

NOT YET RECRUITING

Tel Aviv-Sourasky Medical Center

Tal Aviv, Israel

NOT YET RECRUITING

Sheba Medical Center

Tel Litwinsky, 45858, Israel

RECRUITING

Related Publications (1)

• 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.

  PMID: 24050955 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Propranolol; Etodolac

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Indoleacetic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Oded Zmora, M.D.

CONTACT

972-3-5302247; ozmora@post.post.tau.ac.il

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: April 26, 2009
• First Posted: April 28, 2009
• Study Start: January 1, 2010
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: July 12, 2011

Record last verified: 2011-07

Locations

IL (3)