ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12612000852853

Ethics application status

Approved

Date submitted

8/08/2012

Date registered

14/08/2012

Date last updated

17/08/2012

Type of registration

Prospectively registered

Titles & IDs

Public title

Preventing Colorectal Cancer Metastases following Surgical Removal of a Primary Tumor

Scientific title

Preventing Colorectal Cancer Metastases in adults following Surgical Removal of a Primary Tumor by using a cocktail of a B-blocker and a COX2 inhibitor

Secondary ID [1]

nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Colorectal cancer

Condition category

Condition code

Cancer

Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

In the current study we aim at testing the safety and efficacy of our drug cocktail in patients undergoing excision of colorectal cancer. Both short-term outcomes (immune and endocrine indices), as well as 3-year recurrence rates will be assessed within patients. Specifically, we propose a double blind clinical trial with two major arms: (I) placebo treatment, and (II) treatment with a cocktail of a B-blocker (propranolol – to block catecholamines, oral tablet 40 mg , 3 times daily) and a COX2 inhibitor (etodolac – to block prostaglandin receptors, 200 mg oral tablets every 6 hours ). A total of 206 patients will be recruited. The drug treatment will be given for a total of 20-day period, commencing five days before surgery, with no time overlap with adjuvant therapy, and independently of any other routine therapy. The drug treatment is planned for only 15 post-operative days to reduce potential side effects, and because most immunological and endocrine perturbations induced by surgery dissipate during this period. Immune and endocrine baseline levels will be established in a group of thirty healthy matched control subjects.
Short-term endocrine and immune measures will include: serum levels of various cytokines; serum cortisol, C-reactive protien, Vascular endothelial growth factor, leukocyte subpopulations and their functional markers; and Natural killar cells activity. All indices will be assessed repeatedly within subjects, using freshly drawn blood samples that will be collected twice before surgery (days -5 and on the morning of surgery), and on post-operative days 1 and 3. Resected malignant tumors and normal colonic tissue will be tested for catecolamines (CA) and prostaglandines (PG) receptor expression. Clinical outcomes will include perioperative complication rate and narcotic use, and 2-year recurrence rate.

Intervention code [1]

Prevention

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

Control group receive placebo which are tablets with the same shape and form of the original drug given in the study group

Control group

Placebo

Outcomes

Primary outcome [1]

Tumor recurrence by abdominal CT scan and colonoscope

Timepoint [1]

recurrence survey starts 6 months after surgery and then every 6 months for 2 years

Secondary outcome [1]

Distant metastasis by abdominal and Chest CT scan

Timepoint [1]

metastasis survey starts 6 months after surgery and then every 6 months for at least 2 years

Eligibility

Key inclusion criteria

Adult patient with colorectal cancer, stage II or III

Minimum age

18 Years

Maximum age

70 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Stage IV cancer, liver or renal (kidney) failure , glaucoma, history of immediate allergic reaction (known as anaphylaxis) to a beta blocker of any kind and pheocromocytoma

Study design

Purpose of the study

Prevention

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Double blind clinical trial with two major arms: (I) placebo treatment, and (II) treatment with a cocktail of a beta-blocker (propranolol – to block Catecolamines) and a COX2 inhibitor (etodolac – to block prostaglandines). A total of 206 patients will be recruited.Choice of patients will be done by a person unaware of the study, randomization will be done before surgery by computer randomization. Allocation of a patient to a the treatment or placebo will be concealed by . sealed opaque envelopes

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

computer based randomization

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 2

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

15/08/2012

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

200

Accrual to date

Final

Recruitment outside Australia

Country [1]

Egypt

State/province [1]

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

Egypt

Funding source category [2]

Self funded/Unfunded

Name [2]

Khaled Madbouly

Address [2]

kolyet el teb street, Azarita, faculty of medicine, university of alexandria, Alexandria 21321, Egypt

Country [2]

Egypt

Primary sponsor type

Individual

Name

Khaled Madbouly

Address

kolyet el teb street, Azarita, faculty of medicine, university of alexandria, Alexandria 21321, Egypt

Country

Egypt

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Ethics committee , faculty of medicine, university of Alexandria

Ethics committee address [1]

kolyet el teb street, Azarita, faculty of medicine, university of alexandria, alexandria, 21321, Egypt

Ethics committee country [1]

Egypt

Date submitted for ethics approval [1]

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

: In the current study we aim at testing the safety and efficacy of our drug cocktail in patients undergoing excision of colorectal cancer.  Both short-term outcomes (immune and endocrine indices), as well as 2-year recurrence rates will be assessed within patients. Specifically, we propose a phase II double blind clinical trial with two major arms: (I) placebo treatment, and (II) treatment with a cocktail of a B-blocker (propranolol – to block CAs) and a COX2 inhibitor (etodolac – to block PGs). A total of 206 patients will be recruited along a two year. The drug treatment will be given for a total of 20-day period, commencing five days before surgery, with no time overlap with adjuvant therapy, and independently of any other routine therapy. The drug treatment is planned for only 15 post-operative days to reduce potential side effects, and because most immunological and endocrine perturbations induced by surgery dissipate during this period. Immune and endocrine baseline levels will be established in a group of thirty healthy matched control subjects.
Short-term endocrine and immune measures will include: serum levels of various cytokines; serum cortisol, CRP, VEGF levels; leukocyte subpopulations and their functional markers; and NK number and activity. All indices will be assessed repeatedly within subjects, using freshly drawn blood samples that will be collected twice before surgery (days -5 and on the morning of surgery), and on post-operative days 1 and 3. Resected malignant tumors and normal colonic tissue will be tested for CA and PG receptor expression. Clinical outcomes will include perioperative complication rate and narcotic use, and 2-year recurrence rate. 

We hypothesize that our 20-day pharmacological treatment will: (i) significantly improve the status of the endocrine factors before surgery (e.g., VEGF, CRP, MMP2, MMP9 & cortisol) and enhance CMI competence, (ii) significantly attenuate the profound postoperative suppression of CMI and improve the postoperative endocrine status, and (iii) increase the 3-year recurrence-free survival rate. We further hypothesize that the peri-operative status of some endocrine/immunological indices will predict the 3-year recurrence rate, and that the within-subject alterations in these indices, caused by surgery and/or our drug intervention, will further predict recurrence-free survival rate. Provided that this study will indicate promising outcomes, our long-term plan is to employ this intervention in a larger sample of cancer patients and assess overall long-term survival rates. Such a larger study, powered to exhibit 5-10% improved survival rates, would be justified provided significant improvements in CMI/endocrine indices and/or a trend toward improved 3-year recurrence-free survival rates.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

khaled madbouly

Address

kolyet el teb street, Azarita, faculty of medicine, university of alexandria, alexandria, 21321, Egypt

Country

Egypt

Phone

+20 34802375

Fax

khaled.madbouly@alexmed.edu.eg

Contact person for scientific queries

Name

khaled madbouly

Address

kolyet el teb street, Azarita, faculty of medicine, university of alexandria, alexandria, 21321, Egypt

Country

Egypt

Phone

+20 34802375

Fax

khaled.madbouly@alexmed.edu.eg

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Repurposing drugs in oncology (ReDO) - Propranolol as an anti-cancer agent.	2016	https://dx.doi.org/10.3332/ecancer.2016.680

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added automatically