PERI-OP: Thromboprophylaxis for Patients Undergoing Surgical Resection for Colon Cancer

Sponsor

Ottawa Hospital Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00967148

Collaborator

LEO Pharma (Industry)

Enrollment

Location

Arms

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The blood thinner "tinzaparin" might increase survival in patients with colon cancer undergoing surgical resection. The investigators want to assess if a trial allocating patients to prolonged treatment with tinzaparin versus standard of care is feasible.

Condition or Disease	Intervention/Treatment	Phase
Deep Vein Thrombosis Pulmonary Embolism Cancer	Drug: Tinzaparin	N/A

Detailed Description

Cancer patients are at high risk of postoperative thrombosis and this risk remains elevated beyond the period of hospitalization. Thromboprophylaxis effectively reduces the risk of post operative VTE in cancer patients. Extended thromboprophylaxis beyond hospitalization (up to 30 days) with LMWH has been shown to further reduce the risk of postoperative VTE. Concurrently, there is a growing body of evidence to suggest that LMWH may have anti-cancer effects due to anti-metastatic properties and may improve survival in cancer patients, even in the absence of a documented VTE. Retrospective studies have shown that perioperative thromboprophylaxis (i.e., starting thromboprophylaxis before the surgery) seems to increase survival in cancer patients undergoing abdominal or pelvic cancer surgery with curative intent. The investigators propose to perform an open-label RCT to determine if thromboprophylaxis using tinzaparin 4,500 IU daily, starting from the time of decision to operate through the peri-operative period and extending for 4 weeks postoperatively, is feasible.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

The Use of Extended Perioperative Low Molecular Weight Heparin to Improve Cancer Specific Survival Following Surgical Resection of Colon Cancer: A Pilot Randomized Controlled Trial

Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Sep 1, 2010

Actual Study Completion Date :

Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tinzaparin The treatment arm will receive a subcutaneous injection of tinzaparin (4500U) daily beginning within two days of the decision to operate (within 6 weeks of surgical resection) weeks and continued for 4 weeks following resection.	Drug: Tinzaparin The treatment arm will receive a subcutaneous injection of tinzaparin (4500U) daily beginning within two days of the decision to operate (within 6 weeks of surgical resection) weeks and continued for 4 weeks following resection. Other Names: Innohep
Active Comparator: Standard of care The control arm will receive a subcutaneous injection of 4,500 U of tinzaparin daily beginning with the first postoperative dose and continued for the duration of hospitalization.	Drug: Tinzaparin The treatment arm will receive a subcutaneous injection of tinzaparin (4500U) daily beginning within two days of the decision to operate (within 6 weeks of surgical resection) weeks and continued for 4 weeks following resection. Other Names: Innohep

Arm

Intervention/Treatment

Experimental: Tinzaparin

The treatment arm will receive a subcutaneous injection of tinzaparin (4500U) daily beginning within two days of the decision to operate (within 6 weeks of surgical resection) weeks and continued for 4 weeks following resection.

Drug: Tinzaparin

Other Names:

Innohep

Active Comparator: Standard of care

The control arm will receive a subcutaneous injection of 4,500 U of tinzaparin daily beginning with the first postoperative dose and continued for the duration of hospitalization.

Drug: Tinzaparin

Other Names:

Innohep

Outcome Measures

Primary Outcome Measures

Recruitment rate [3 months]

Secondary Outcome Measures

Refusal rate [3 months]
Rate of non-compliance and lost to follow-up [6 months]
Expression of sialylated fucosylated glycans (including CA19-9, sialyl Lewis X and CD24) in primary tumor specimens by immunohistochemistry (IHC). [postoperative day 0, 1, 4, 7±1, and 28±4]
Expression of TF. VEGF and microvessel density in primary tumor specimens by IHC. [postoperative day 0, 1, 4, 7±1, and 28±4]
Serum soluble TF and TFPI levels pre and postoperatively (postoperative day 0, 1, 4, 7±1, and 28±4) measured by enzyme linked immunosorbent assay (ELISA). [postoperative day 0, 1, 4, 7±1, and 28±4]
Platelet count and serum soluble P-selectin levels pre and postoperatively (postoperative day 0, 1, 4, 7±1, and 28±4) measured by hemocytometer and ELISA. [postoperative day 0, 1, 4, 7±1, and 28±4]
Serum VEGF levels pre and postoperatively (postoperative day 0, 1, 4, 7±1, and 28±4) measured by ELISA [postoperative day 0, 1, 4, 7±1, and 28±4]
Quantification and characterization of VPC pre and postoperatively (postoperative day 0, 1, 4, 7±1, and 28±4) measured by VPC cell culture assay and flow cytometry. [postoperative day 0, 1, 4, 7±1, and 28±4]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males or females aged 18 years or older with a pathologically confirmed localized invasive colorectal cancer and no evidence of metastatic disease who are scheduled to undergo surgical resection will be eligible.
All study patients must be enrolled at least two weeks prior to scheduled surgery and provide written informed consent.
All the following criteria must be met to be eligible:

Pathological confirmation of an invasive adenocarcinoma of the colon;
No evidence of metastatic disease by Computed Tomography (CT) scan of the abdomen and pelvis or chest X-ray (CXR). A Magnetic Resonance Imaging (MRI) of the abdomen and pelvis will be used if the patient has a documented contrast allergy or to verify a questionable finding on the CT scan. Any abnormal findings on CXR will be investigated with a CT scan of the chest. Imaging must be performed within 2 months of randomization;
a scheduled surgical operation for resection of the colon cancer; and
ECOG performance status 0 or 1.

Exclusion Criteria:

Subjects cannot be included in this study if any of the following criteria apply:

rectal adenocarcinoma (defined as tumor below the peritoneal reflection or within 12 cm of the anal verge by rigid sigmoidoscopy);
prior VTE including deep vein thrombosis (DVT) or pulmonary embolism (PE);
requirement for full dose perioperative anticoagulation;
requirement for anti-platelet or anti-inflammatory therapy that cannot be discontinued;
contraindication to heparin therapy **;
geographic inaccessibility (less likely to comply with required follow-up visits and care);
participating in another interventional trial that may result in co-intervention or contamination (to be determined by PI);
< 18 years of age;
history of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years of the colorectal cancer diagnosis;
treatment, including radiation therapy, chemotherapy or targeted therapy, administered for the currently diagnosed colon cancer prior to randomization;
pregnant or lactating; and
unable/unwilling to providing informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ottawa Health Research Institute	Ottawa	Ontario	Canada	K1H 8L6

Sponsors and Collaborators

Ottawa Hospital Research Institute
LEO Pharma

Investigators

Principal Investigator: Marc Carrier, MD MSc, Ottawa Hospital Research Institute
Principal Investigator: Rebecca Auer, MD MSc, Ottawa Hospital Research Institute
Study Chair: Tim Asmis, MD, Ottawa Hospital