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

Ottawa Hospital Research Institute

Status and phase: Completed; Phase 3

Conditions: Adenocarcinoma of the Colon

Treatments: Drug: Tinzaparin

Study type: Interventional

Funder types: Other

Identifiers

NCT01455831

221097

Details and patient eligibility

About

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.

Enrollment: 616 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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616 participants in 2 patient groups

Extended peri-operative thromboprophylaxis

Experimental group

Description:

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.

Treatment:

Drug: Tinzaparin

Drug: Tinzaparin

Standard thromboprophylaxis

Active Comparator group

Description:

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.

Treatment:

Drug: Tinzaparin

Drug: Tinzaparin