Clinical trial NCT01455831: Extended Peri-operative Tinzaparin to Improve Disease-free Survival in Patients With Resectable Colorectal Cancer
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 Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Adenocarcinoma of the Colon
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2011-10-20
Enrollment: 616
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Disease Free Survival
timeFrame: measured at 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: measured at 5 years
measure: Venous Thromboembolism events
timeFrame: From randomization until 56 days post-surgery
measure: Major surgical site bleeding events
timeFrame: From randomization until 56 days post-surgery
measure: Major bleeding events (not including the surgical site)
timeFrame: From randomization until 56 days post-surgery
measure: • Clinically relevant bleeding events prior to surgery and during the • Clinically relevant bleeding events
timeFrame: From randomization to 56 days post-surgery
measure: Transfusion requirements
timeFrame: From randomization to 56 days post-surgery
measure: Correlative endpoints
timeFrame: 5 years
measure: Other post-operative (day 0 - day 28) complications
timeFrame: Measured from Day 0 until day 28 post-operatively
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Research Institute
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Montfort Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Queensway Carleton Hospital
state: Ontario
city: Sault Ste. Marie
country: Canada
facility: Sault Area Hospital
state: Ontario
city: Sudbury
country: Canada
facility: Health Sciences North
state: Ontario
city: Toronto
country: Canada
facility: Humber River Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: North York General Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Joseph's Health Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Brest
country: France
facility: CHRU Brest
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Marc Carrier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Hospital Research Institute
name: Rebecca Ann Auer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Auer RC, Ott M, Karanicolas P, Brackstone MR, Ashamalla S, Weaver J, Tagalakis V, Boutros M, Stotland P, Marulanda AC, Moloo H, Jayaraman S, Patel S, Le Gal G, Spadafora S, MacLellan S, Trottier D, Jonker D, Asmis T, Mallick R, Pecarskie A, Ramsay T, Carrier M; PERIOP-01 investigators. Efficacy and safety of extended duration to perioperative thromboprophylaxis with low molecular weight heparin on disease-free survival after surgical resection of colorectal cancer (PERIOP-01): multicentre, open label, randomised controlled trial. BMJ. 2022 Sep 13;378:e071375. doi: 10.1136/bmj-2022-071375.