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Thromboprophylaxis for Patients Undergoing Surgical Resection for Colon Cancer

Not Applicable
Completed
Conditions
Pulmonary Embolism
Deep Vein Thrombosis
Cancer
Interventions
Registration Number
NCT00967148
Lead Sponsor
Ottawa Hospital Research Institute
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
18
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:

    1. Pathological confirmation of an invasive adenocarcinoma of the colon;
    2. 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;
    3. a scheduled surgical operation for resection of the colon cancer; and
    4. ECOG performance status 0 or 1.
Exclusion Criteria
  • Subjects cannot be included in this study if any of the following criteria apply:

    1. rectal adenocarcinoma (defined as tumor below the peritoneal reflection or within 12 cm of the anal verge by rigid sigmoidoscopy);
    2. prior VTE including deep vein thrombosis (DVT) or pulmonary embolism (PE);
    3. requirement for full dose perioperative anticoagulation;
    4. requirement for anti-platelet or anti-inflammatory therapy that cannot be discontinued;
    5. contraindication to heparin therapy **;
    6. geographic inaccessibility (less likely to comply with required follow-up visits and care);
    7. participating in another interventional trial that may result in co-intervention or contamination (to be determined by PI);
    8. < 18 years of age;
    9. 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;
    10. treatment, including radiation therapy, chemotherapy or targeted therapy, administered for the currently diagnosed colon cancer prior to randomization;
    11. pregnant or lactating; and
    12. unable/unwilling to providing informed consent.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Standard of careTinzaparinThe 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.
TinzaparinTinzaparinThe 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.
Primary Outcome Measures
NameTimeMethod
Recruitment rate3 months
Secondary Outcome Measures
NameTimeMethod
Serum VEGF levels pre and postoperatively (postoperative day 0, 1, 4, 7±1, and 28±4) measured by ELISApostoperative day 0, 1, 4, 7±1, and 28±4
Rate of non-compliance and lost to follow-up6 months
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 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
Refusal rate3 months
Expression of TF. VEGF and microvessel density in primary tumor specimens by IHC.postoperative day 0, 1, 4, 7±1, and 28±4
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
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

Trial Locations

Locations (1)

Ottawa Health Research Institute

🇨🇦

Ottawa, Ontario, Canada

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