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Trial record 49 of 127 for:    colon cancer | ( Map: Canada )

Extended Peri-operative Tinzaparin to Improve Disease-free Survival in Patients With Resectable Colorectal Cancer (PERIOP-01)

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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01455831
Recruitment Status : Recruiting
First Posted : October 20, 2011
Last Update Posted : July 22, 2019
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Tracking Information
First Submitted Date  ICMJE October 18, 2011
First Posted Date  ICMJE October 20, 2011
Last Update Posted Date July 22, 2019
Study Start Date  ICMJE September 2011
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2011)
Disease Free Survival [ Time Frame: measured at 3 years ]
Disease free survival is measured from the time of randomization until local disease recurrence, distant disease recurrence, a new primary colon cancer malignancy, other second primary cancer or death from any cause.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01455831 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2013)
  • Overall Survival [ Time Frame: measured at 5 years ]
    Death from any cause
  • Venous Thromboembolism events [ Time Frame: From randomization until 56 days post-surgery ]
    • VTE events defined as: a. Deep vein thrombosis: i. non-compressibility of any vein segment from the common femoral vein to the trifurcation of the popliteal vein on compressive ultrasonography ii.persistent intra-luminal filling defect of the iliac, common femoral, superficial femoral, popliteal, posterior tibial or peroneal veins on contrast venography b. Pulmonary embolism: i.high probability V/Q scan ii.positive pulmonary angiogram iii.spiral CT demonstrating intraluminal filling defect in a vessel larger than a segmental artery
  • Major surgical site bleeding events [ Time Frame: From randomization until 56 days post-surgery ]
    • Major surgical site bleeding events defined as bleeding at the surgical site associated with:
    1. requirement for ≥4 units of packed red blood cells
    2. a drop in Hb of >40 g/L during the first post-op week
    3. bleeding requiring re-operation
    4. fatal bleeding
  • Major bleeding events (not including the surgical site) [ Time Frame: From randomization until 56 days post-surgery ]
    • Major bleeding events (not including the surgical site) defined as:
    1. fatal bleeding, and/or
    2. symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or,
    3. bleeding causing a fall in hemoglobin level of ≥20 g/L, or leading to transfusion of ≥2 units of whole blood or red cells.
  • • Clinically relevant bleeding events prior to surgery and during the • Clinically relevant bleeding events [ Time Frame: From randomization to 56 days post-surgery ]
    Clinically relevant bleeding events prior to surgery and during the follow-up period will be defined as overt bleeding episodes not meeting the inclusion for major bleeding but associated with one of the following:
    1. medical intervention;
    2. an unscheduled contact with a physician;
    3. temporary cessation of anticoagulant treatment
  • Transfusion requirements [ Time Frame: From randomization to 56 days post-surgery ]
    Transfusion requirements using the number of units transfused:
    1. Red blood cells
    2. Platelets (Adult dose)
    3. Frozen Plasma
  • Correlative endpoints [ Time Frame: 5 years ]
    The correlative endpoints seek to evaluate the pro-metastatic mechanisms of surgery and the antimetastatic mechanisms of LMWH in subjects undergoing surgical resection for colon cancer.
  • Other post-operative (day 0 - day 28) complications [ Time Frame: Measured from Day 0 until day 28 post-operatively ]
    Other post-operative (day 0 - day 28) complications as defined using the modified Clavien Classification
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2011)
  • Overall Survival [ Time Frame: measured at 5 years ]
    Death from any cause
  • Venous Thromboembolism events [ Time Frame: Measured until 5 years post operatively ]
    • VTE events defined as: a. Deep vein thrombosis: i. non-compressibility of any vein segment from the common femoral vein to the trifurcation of the popliteal vein on compressive ultrsonography ii.persistent intra-luminal filling defect of the iliac, common femoral, superficial femoral, popliteal, posterior tibial or peroneal veins on contrast venography b. Pulmonary embolism: i.high probability V/Q scan ii.positive pulmonary angiogram iii.spiral CT demonstrating intraluminal filling defect in a vessel larger than a segmental artery
  • Major post-operative bleeding events [ Time Frame: Measured until 5 years post operatively ]
    • Major post-operative (during hospitalization) bleeding events defined as:
    1. requirement for ≥4 units of packed red blood cells
    2. a drop in Hb of >40 g/dL during the first post-op week
    3. bleeding requiring re-operation
    4. intracranial bleeding
    5. fatal bleeding
  • Major bleeding events during follow-up [ Time Frame: Measured until 5 years post operatively ]
    Major bleeding events during follow-up defined as:
    1. fatal bleeding, and/or
    2. symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or,
    3. bleeding causing a fall in hemoglobin level of >20 g/L, or leading to transfusion of >2 units of whole blood or red cells
  • Minor bleeding events [ Time Frame: Measured until 5 years post operatively ]
    Minor bleeding events prior to surgery, during surgery and during follow-up period and will be defined as any bleeding not meeting the requirements of a major bleeding event
  • Transfusion requirements [ Time Frame: Measured until 5 years post operatively ]
    Transfusion requirements using the number of units transfused:
    1. Red blood cells
    2. Platelets (Adult dose)
    3. Frozen Plasma
  • Correlative endpoints [ Time Frame: 9 years ]
    The correlative endpoints seek to evaluate the pro-metastatic mechanisms of surgery and the antimetastatic mechanisms of LMWH in subjects undergoing surgical resection for colon cancer.
  • Other post-operative (day 0 - day 28) complications [ Time Frame: Measured from Day 0 until day 28 post-operatively ]
    Other post-operative (day 0 - day 28) complications as defined using the modified Clavien Classification
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Extended Peri-operative Tinzaparin to Improve Disease-free Survival in Patients With Resectable Colorectal Cancer
Official Title  ICMJE A Multicentre Randomized Controlled Trial of the Use of Extended Peri-Operative Low Molecular Weight Heparin to Improve Cancer Specific Survival Following Surgical Resection of Colorectal Cancer
Brief Summary

The human body has a natural stress response to surgery, including the formation of blood clots. This response to surgery has been shown to increase metastases (the spread of cancer cells to other organs in the body). These metastases cannot be seen at the time of surgery but when they grow into new tumors, the cancer has recurred (come back). A blood thinner called "low molecular weight heparin" (LMWH) can suppress the development of metastases after surgery in animal experiments. The investigators want to see if giving patients with colorectal cancer the blood thinner, LMWH, around the time of surgery can decrease the chance of their cancer spreading to other organs (metastases) and coming back (recurrence).

The investigators need 1075 patients to answer our scientific question. Patients who give informed consent will be randomly put into one of two groups, the experimental group and the control group. The patients in the control group will be treated with LMWH starting a few hours after surgery and every day until they leave the hospital. This is how most patients are treated after colon cancer surgery (standard care). The patients in the experimental group will be treated with LMWH for a longer period of time, starting on the day they agree to have surgery and continuing for two months after surgery. All the patients will be followed for at least three years after surgery to find out if their cancer has recurred (come back). If LMWH treatment around the time of surgery reduces the chance of recurrence in patients with colorectal cancer, it would improve the health and quality of life for these patients.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Adenocarcinoma of the Colon
Intervention  ICMJE
  • Drug: Tinzaparin
    The experimental arm will receive a subcutaneous injection of 4,500 IU of tinzaparin daily beginning at randomization and continued for 56 days following resection. There will be a minimum of one dose of pre-operative LMWH since it is not reasonable to delay surgery for the purpose of administering LMWH. The maximum duration of pre-operative LMWH will be 6 weeks.
    Other Name: Innohep
  • Drug: Tinzaparin
    The control arm will receive a daily subcutaneous injection of 4,500 IU of tinzaparin beginning with the first post-operative dose and continued for the duration of hospitalization.
    Other Name: Innohep
Study Arms  ICMJE
  • Experimental: Extended peri-operative thromboprophylaxis
    The experimental arm will receive a subcutaneous injection of 4,500 IU of tinzaparin daily beginning at randomization and continued for 56 days following resection. There will be a minimum of one dose of pre-operative LMWH since it is not reasonable to delay surgery for the purpose of administering LMWH. The maximum duration of pre-operative LMWH will be 6 weeks.
    Intervention: Drug: Tinzaparin
  • Active Comparator: Standard thromboprophylaxis
    The control arm will receive a daily subcutaneous injection of 4,500 IU of tinzaparin beginning with the first post-operative dose and continued for the duration of hospitalization.
    Intervention: Drug: Tinzaparin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 19, 2011)
1075
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosis of pathologically-confirmed invasive adenocarcinoma of the colon or rectum
  2. Pre-operative work-up that reveals potential resectability (CT scan or MRI of the abdomen and pelvis) with resection planned within 6 weeks of date of randomization
  3. Pre-operative work-up that reveals no evidence of metastatic disease (CT scan or MRI of the abdomen and pelvis and chest X-ray (CXR) or CT scan of the chest)
  4. Age ≥18 years
  5. Hemoglobin ≥ 80g/L
  6. Able and willing to comply with study procedures and follow-up examinations contained within the written consent form.

Exclusion Criteria:

  1. Carcinoma only present in a completely excised polyp (i.e. no residual tumour evident in the colon)
  2. Prior VTE including deep vein thrombosis (DVT) or pulmonary embolism (PE)
  3. Requirement for full dose peri-operative anticoagulation
  4. Contraindication to heparin therapy

    1. history of heparin induced thrombocytopenia (HIT)
    2. platelet count of less than 100 x 109/L
    3. actively bleeding
    4. severe hypertension (SBP >200 and/or DBP >120) on more than one reading
    5. documented peptic ulcer within 6 weeks
    6. severe hepatic failure (INR >1.8)
    7. creatinine clearance of < 30 ml/min as calculated by the Cockcroft-Gault formula
    8. Other contraindication to anticoagulation
  5. Participating in another interventional trial that may result in co-intervention or contamination (to be determined by sponsor)
  6. 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
  7. Pregnant or lactating
  8. Unable/unwilling to providing informed consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lesley Yeung, BSc 613-737-8899 ext 72998 lyeung@ohri.ca
Contact: Penny Phillips, MA 613-737-8899 ext 73440 pphillips@ohri.ca
Listed Location Countries  ICMJE Canada,   Belgium,   France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01455831
Other Study ID Numbers  ICMJE 221097
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ottawa Hospital Research Institute
Study Sponsor  ICMJE Ottawa Hospital Research Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marc Carrier, MD Ottawa Hospital Research Institute
Principal Investigator: Rebecca Ann Auer, MD Ottawa Hospital Research Institute
PRS Account Ottawa Hospital Research Institute
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP