Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01455831
Other study ID # 221097
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date September 2011
Est. completion date February 1, 2021

Study information

Verified date May 2021
Source Ottawa Hospital Research Institute
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 616
Est. completion date February 1, 2021
Est. primary completion date December 31, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Intervention

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.
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.

Locations

Country Name City State
Belgium Ghent University Hospital Ghent
Canada Hamilton Health Sciences Corporation Hamilton Ontario
Canada Kingston General Hospital Kingston Ontario
Canada London Health Research Institute London Ontario
Canada Jewish General Hospital Montreal Quebec
Canada Montfort Hospital Ottawa Ontario
Canada Queensway Carleton Hospital Ottawa Ontario
Canada The Ottawa Hospital Ottawa Ontario
Canada Sault Area Hospital Sault Ste. Marie Ontario
Canada Health Sciences North Sudbury Ontario
Canada Humber River Hospital Toronto Ontario
Canada Mount Sinai Hospital Toronto Ontario
Canada North York General Hospital Toronto Ontario
Canada St. Joseph's Health Centre Toronto Ontario
Canada Sunnybrook Health Science Centre Toronto Ontario
France CHRU Brest Brest

Sponsors (1)

Lead Sponsor Collaborator
Ottawa Hospital Research Institute

Countries where clinical trial is conducted

Belgium,  Canada,  France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Disease Free Survival 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. measured at 3 years
Secondary Overall Survival Death from any cause measured at 5 years
Secondary Venous Thromboembolism events • 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
From randomization until 56 days post-surgery
Secondary Major surgical site bleeding events • Major surgical site bleeding events defined as bleeding at the surgical site associated with:
requirement for =4 units of packed red blood cells
a drop in Hb of >40 g/L during the first post-op week
bleeding requiring re-operation
fatal bleeding
From randomization until 56 days post-surgery
Secondary Major bleeding events (not including the surgical site) • Major bleeding events (not including the surgical site) defined as:
fatal bleeding, and/or
symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or,
bleeding causing a fall in hemoglobin level of =20 g/L, or leading to transfusion of =2 units of whole blood or red cells.
From randomization until 56 days post-surgery
Secondary • Clinically relevant bleeding events prior to surgery and during the • Clinically relevant bleeding events 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:
medical intervention;
an unscheduled contact with a physician;
temporary cessation of anticoagulant treatment
From randomization to 56 days post-surgery
Secondary Transfusion requirements Transfusion requirements using the number of units transfused:
Red blood cells
Platelets (Adult dose)
Frozen Plasma
From randomization to 56 days post-surgery
Secondary Correlative endpoints 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. 5 years
Secondary Other post-operative (day 0 - day 28) complications Other post-operative (day 0 - day 28) complications as defined using the modified Clavien Classification Measured from Day 0 until day 28 post-operatively
See also
  Status Clinical Trial Phase
Completed NCT00025337 - Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated Phase 3
Completed NCT03871959 - Pembrolizumab In Combination With Debio 1143 In Pancreatic and Colorectal Advanced/Metastatic Adenocarcinoma Phase 1
Recruiting NCT05080673 - Five or Ten Year Colonoscopy for 1-2 Non-Advanced Adenomatous Polyps N/A
Completed NCT01037790 - Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer Phase 2
Completed NCT00707889 - Phase 2 Study of ABT-869 in Combination With mFOLFOX6 Versus Bevacizumab in Combination With mFOLFOX6 to Treat Advanced Colorectal Cancer Phase 2
Completed NCT00551421 - Pertuzumab and Cetuximab in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer Phase 1/Phase 2
Terminated NCT00052585 - Gefitinib and Combination Chemotherapy in Treating Patients With Advanced or Recurrent Colorectal Cancer Phase 2
Completed NCT00023933 - Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Recurrent or Persistent Metastatic Colorectal Cancer Phase 1
Terminated NCT00397878 - AZD0530 (NSC 735464) in Treating Patients With Previously Treated Metastatic Colon Cancer or Rectal Cancer Phase 2
Completed NCT00028496 - Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer Phase 1
Recruiting NCT04005118 - Human Intestinal Microbiome and Surgical Outcomes in Patients Undergoing Colorectal Cancer Surgery
Completed NCT00003835 - Combination Chemotherapy in Treating Patients With Stage III Colon Cancer Phase 3
Terminated NCT02425683 - Study of Colorectal Cancer Patients (Stage IIIC) With Either Regorafenib or Standard of Care (No Treatment) After Adjuvant FOLFOX Phase 2
Recruiting NCT05669430 - A Study of GV20-0251 in Patients With Solid Tumor Malignancies Phase 1
Completed NCT00005818 - SU5416 and Irinotecan in Treating Patients With Advanced Colorectal Cancer Phase 1/Phase 2
Recruiting NCT04624555 - The Utility and Feasibility of Mt-sDNA as a Surveillance Procedure in Colorectal Cancer Survivors
Terminated NCT01606124 - Polyphenon E in Treating Patients With High-Risk of Colorectal Cancer Phase 2
Completed NCT00942266 - Vorinostat, Fluorouracil, and Leucovorin Calcium in Treating Patients With Metastatic Colorectal Cancer That Has Not Responded to Previous Treatment Phase 2
Recruiting NCT05197322 - NEOadjuvant PembRolizumab In Stratified Medicine - ColoRectal Cancer Phase 2
Completed NCT00397384 - Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer Phase 1