Colorectal NeoplasmsPhase 3NCT00888797
β-adrenergic Blocker and a COX2 Inhibitor for Prevention of Colorectal Cancer Recurrence
A Phase 3 study testing Propranolol and Etodolac in people with Colorectal Neoplasms, run by Sheba Medical Center at 3 sites in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- Propranolol and Etodolac
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 400 participants
- Where
- 3 sitesIsrael
- Study dates
- Jan 2010to Jan 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 27Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
Israel3 sites, 3 recruiting
- Not yet recruiting
Rabin- Beilinson Medical Center
Petah Tikva
Nir Wasserberg, M.D., nirw@clalit.org.il
Nir Wasserberg, M.D.
- Not yet recruiting
Tel Aviv-Sourasky Medical Center
Tal Aviv
Hagit Tulchinsky, M.D., hagitt@tasmc.health.gov.il
Hagit Tulchinsky, M.D.
- Recruiting
Sheba Medical Center
Tel HaShomer, 45858
Oded Zmora, M.D., 972-3-5302247, ozmora@post.tau.ac.il
Oded Zmora, M.D.
About this study
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.
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
- Being tested
- Propranolol and Etodolac
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Propranolol and EtodolacDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Perioperative Propranolol and Etodolac Receives: Drug: Propranolol and Etodolac |
| 2 | Placebo comparator | Placebo Receives: Drug: Propranolol and Etodolac |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of recurrent and metastatic cancer
Measured: 3 years
Secondary outcomes (2)
magnitude and duration of surgically induced immune depression, as reflected in the blood samples
Measured: early postoperative
Early postoperative morbidity and mortality
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2009 (estimated)
- Study startJan 2010
- Primary completionJan 2017 (estimated)
- Study completionJan 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Collaborators
- Tel-Aviv Sourasky Medical Center, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00888797
- Sponsor's protocol ID
- SHEBA-09-6994-OZ-CTIL
- Status last verified
- Jul 2011
- First submitted
- 26 Apr 2009
- Last updated
- 12 Jul 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Sakis N, Sorski L, Asraf E, Ricon-Becker I, Shaashua L, Haldar R, Shvalbo BB, Shabat-Simon M, Gutman M, Nissan A, Nachmany I, Kent I, Pery R, Pencovich N, Shussman N, Wasserberg N, Reshef A, Quint E, Lishtzinsky YY, Kashtan H, Shabtai M, Brenner B, Sharon E, Allweis T, Shahar N, Eckerling A, Sandbank E, Zmora O, Ben-Eliyahu S. Favorable safety outcomes of a perioperative propranolol and etodolac regimen in cancer patients in four randomized controlled trials. Front Pharmacol. 2026 Apr 20;17:1823113. doi: 10.3389/fphar.2026.1823113. eCollection 2026.
PubMed 42088573Hicks 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.
PubMed 24050955
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00888797
- Acronym / sponsor ID
- SHEBA-09-6994-OZ-CTIL
- Conditions
- Colorectal Neoplasms
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Collaborators
- Tel-Aviv Sourasky Medical Center, Rabin Medical Center
- Study start
- Jan 2010
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Jan 2017 (estimated)
- First posted
- 28 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Propranolol and EtodolacPerioperative Propranolol and Etodolac |
| 2 | Placebo comparator | Drug: Propranolol and EtodolacPlacebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (27 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Propranolol and EtodolacBoth 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. | Drug | 1, 2 |
Primary outcome
Rate of recurrent and metastatic cancer
Time frame: 3 years
2 secondary outcomes
magnitude and duration of surgically induced immune depression, as reflected in the blood samples
Time frame: early postoperative
Early postoperative morbidity and mortality
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2011.
- Derived from this study: PubMed 42088573Sakis N, Sorski L, Asraf E, Ricon-Becker I, Shaashua L, Haldar R, Shvalbo BB, Shabat-Simon M, Gutman M, Nissan A, Nachmany I, Kent I, Pery R, Pencovich N, Shussman N, Wasserberg N, Reshef A, Quint E, Lishtzinsky YY, Kashtan H, Shabtai M, Brenner B, Sharon E, Allweis T, Shahar N, Eckerling A, Sandbank E, Zmora O, Ben-Eliyahu S. Favorable safety outcomes of a perioperative propranolol and etodolac regimen in cancer patients in four randomized controlled trials. Front Pharmacol. 2026 Apr 20;17:1823113. doi: 10.3389/fphar.2026.1823113. eCollection 2026.
- Derived from this study: PubMed 24050955Hicks 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Propranolol and Etodolac in people with Colorectal Neoplasms, run by Sheba Medical Center at 3 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jul 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Oded Zmora, M.D. (972-3-5302247, ozmora@post.post.tau.ac.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of recurrent and metastatic cancer (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00888797, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2011.