The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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] 280989 0
nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal cancer 287118 0
Condition category
Condition code
Cancer 287439 287439 0 0
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] 285437 0
Prevention
Intervention code [2] 285443 0
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] 287705 0
Tumor recurrence by abdominal CT scan and colonoscope
Timepoint [1] 287705 0
recurrence survey starts 6 months after surgery and then every 6 months for 2 years
Secondary outcome [1] 298660 0
Distant metastasis by abdominal and Chest CT scan
Timepoint [1] 298660 0
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
Gender
Both males and females
Can healthy volunteers participate?
No
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
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 4464 0
Egypt
State/province [1] 4464 0

Funding & Sponsors
Funding source category [1] 285778 0
Self funded/Unfunded
Name [1] 285778 0
Address [1] 285778 0
Country [1] 285778 0
Egypt
Funding source category [2] 285808 0
Self funded/Unfunded
Name [2] 285808 0
Khaled Madbouly
Address [2] 285808 0
kolyet el teb street, Azarita, faculty of medicine, university of alexandria, Alexandria 21321, Egypt
Country [2] 285808 0
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] 284601 0
None
Name [1] 284601 0
Address [1] 284601 0
Country [1] 284601 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287785 0
Ethics committee , faculty of medicine, university of Alexandria
Ethics committee address [1] 287785 0
kolyet el teb street, Azarita, faculty of medicine, university of alexandria, alexandria, 21321, Egypt
Ethics committee country [1] 287785 0
Egypt
Date submitted for ethics approval [1] 287785 0
Approval date [1] 287785 0
Ethics approval number [1] 287785 0

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 34549 0
Address 34549 0
Country 34549 0
Phone 34549 0
Fax 34549 0
Email 34549 0
Contact person for public queries
Name 17796 0
khaled madbouly
Address 17796 0
kolyet el teb street, Azarita, faculty of medicine, university of alexandria, alexandria, 21321, Egypt
Country 17796 0
Egypt
Phone 17796 0
+20 34802375
Fax 17796 0
Email 17796 0
khaled.madbouly@alexmed.edu.eg
Contact person for scientific queries
Name 8724 0
khaled madbouly
Address 8724 0
kolyet el teb street, Azarita, faculty of medicine, university of alexandria, alexandria, 21321, Egypt
Country 8724 0
Egypt
Phone 8724 0
+20 34802375
Fax 8724 0
Email 8724 0
khaled.madbouly@alexmed.edu.eg

No information has been provided regarding IPD availability
Summary results
No Results