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

This study is currently recruiting participants.
Verified December 2013 by Ottawa Hospital Research Institute
Sponsor:
Information provided by (Responsible Party):
Marc Carrier, MD, Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT01455831
First received: October 18, 2011
Last updated: December 5, 2013
Last verified: December 2013
  Purpose

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 colon 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 colon cancer, it would improve the health and quality of life for these patients.


Condition Intervention Phase
Adenocarcinoma of the Colon
Drug: Tinzaparin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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 Colon Cancer

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Disease Free Survival [ Time Frame: measured at 3 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: measured at 5 years ] [ Designated as safety issue: No ]
    Death from any cause

  • Venous Thromboembolism events [ Time Frame: From randomization until 56 days post-surgery ] [ Designated as safety issue: No ]

    • 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 ] [ Designated as safety issue: Yes ]

    • 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 ] [ Designated as safety issue: Yes ]

    • 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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Other post-operative (day 0 - day 28) complications as defined using the modified Clavien Classification


Estimated Enrollment: 1075
Study Start Date: September 2011
Estimated Study Completion Date: August 2023
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- 1. Diagnosis of pathologically-confirmed invasive adenocarcinoma of the colon 2. Pre-operative work-up that reveals potential resectability (CT scan or MRI of the abdomen and pelvis within 90 days 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 within 90 days of randomization) 4. A planned surgical operation for resection of the colon cancer within 6 weeks from the date of randomization 5. ECOG performance status 0 or 1 6. Age ≥18 years 7. Hemoglobin ≥ 80g/L 8. Able and willing to sign Research Ethics Board (REB)-approved written consent form 9. Able and willing to comply with study procedures and follow-up examinations contained within the written consent form.

Exclusion Criteria:

- 1. Rectal adenocarcinoma (defined as tumour below the peritoneal reflection on imaging or within 15 cm of the anal verge by rigid sigmoidoscopy) 2. Carcinoma only present in a completely excised polyp (i.e. no residual tumour evident in the colon) 3. Prior VTE including deep vein thrombosis (DVT) or pulmonary embolism (PE) 4. Requirement for full dose peri-operative anticoagulation 5. 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. heparin or pork allergy
  9. Other contraindication to anticoagulation 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 sponsor) 8. 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 9. Treatment, including radiation therapy, chemotherapy or targeted therapy, administered for the currently diagnosed colon cancer prior to randomization 10. Pregnant or lactating 11. Unable/unwilling to providing informed consent.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01455831

Contacts
Contact: Penny Phillips, MA 613-737-8899 ext 73440 pphillips@ohri.ca

Locations
Canada, Ontario
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Anne Haspect, RN    613-737-8899 ext 71064    ahaspect@ohri.ca   
Principal Investigator: Rebecca Ann, C Auer, MD, FRCSC, FACS         
Queensway Carleton Hospital Recruiting
Ottawa, Ontario, Canada
Contact: Anne Haspect, RN       ahaspect@ohri.ca   
Principal Investigator: Joel Weaver, MD         
Montfort Hospital Not yet recruiting
Ottawa, Ontario, Canada
Contact: Gregoire Le Gal, MD       gregoirelegal@montfort.on.ca   
Principal Investigator: Gregoire Le Gal, MD         
Sunnybrook Health Science Centre Recruiting
Toronto, Ontario, Canada
Contact: Madeline Lemke, BSc       Madeline.Lemke@Sunnybrook.ca   
Principal Investigator: Paul Karanicolas, MD, PhD         
North York General Hospital Not yet recruiting
Toronto, Ontario, Canada
Contact: Madeline Lemke, BSc.       madeline.lemke@nygh.on.ca   
Principal Investigator: Peter Stotland, MD         
Canada, Quebec
Jewish General Hospital Recruiting
Montreal, Quebec, Canada
Contact: Elena Shulikovsky       eshulikovsky@jgh.mcgill.ca   
Principal Investigator: Vicky Tagalakis, MD         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Investigators
Principal Investigator: Marc Carrier Ottawa Hospital Research Institute
Principal Investigator: Rebecca Ann Auer Ottawa Hospital Research Institute
  More Information

No publications provided

Responsible Party: Marc Carrier, MD, MD, Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT01455831     History of Changes
Other Study ID Numbers: 221097
Study First Received: October 18, 2011
Last Updated: December 5, 2013
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Adenocarcinoma
Colonic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Heparin, Low-Molecular-Weight
Dalteparin
Tinzaparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on April 15, 2014