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

NCT01455831 | Completed Phase 3 DMC

• 1 other identifier: 221097
• Study Type: interventional
• Target: 616
• Locations: 3 countries
• Sites: 16

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.

Conditions

Adenocarcinoma of the Colon

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Overall Survival

  measured at 5 years

• Venous Thromboembolism events

  From randomization until 56 days post-surgery

• Major surgical site bleeding events

  From randomization until 56 days post-surgery

• Major bleeding events (not including the surgical site)

  From randomization until 56 days post-surgery

• • Clinically relevant bleeding events prior to surgery and during the • Clinically relevant bleeding events

  From randomization to 56 days post-surgery

Study Arms (2)

Extended peri-operative thromboprophylaxis

EXPERIMENTAL

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

Standard thromboprophylaxis

ACTIVE COMPARATOR

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

Interventions

Tinzaparin DRUG

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.

Also known as: Innohep

Extended peri-operative thromboprophylaxis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of pathologically-confirmed invasive adenocarcinoma of the colon or rectum
• 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
• 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)
• Age ≥18 years
• Hemoglobin ≥ 80g/L
• Able and willing to comply with study procedures and follow-up examinations contained within the written consent form.

You may not qualify if:

• Carcinoma only present in a completely excised polyp (i.e. no residual tumour evident in the colon)
• Prior VTE including deep vein thrombosis (DVT) or pulmonary embolism (PE)
• Requirement for full dose peri-operative anticoagulation
• Contraindication to heparin therapy
• history of heparin induced thrombocytopenia (HIT)
• platelet count of less than 100 x 109/L
• actively bleeding
• severe hypertension (SBP \>200 and/or DBP \>120) on more than one reading
• documented peptic ulcer within 6 weeks
• severe hepatic failure (INR \>1.8)
• creatinine clearance of \< 30 ml/min as calculated by the Cockcroft-Gault formula
• Other contraindication to anticoagulation
• Participating in another interventional trial that may result in co-intervention or contamination (to be determined by sponsor)
• 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
• Pregnant or lactating

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (16)

Ghent University Hospital

Ghent, Belgium

Location

Health Sciences North

Greater Sudbury, Ontario, Canada

Location

Hamilton Health Sciences Corporation

Hamilton, Ontario, L8L 8E7, Canada

Location

Kingston General Hospital

Kingston, Ontario, Canada

Location

London Health Research Institute

London, Ontario, N6C 2R5, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Montfort Hospital

Ottawa, Ontario, Canada

Location

Queensway Carleton Hospital

Ottawa, Ontario, Canada

Location

Sault Area Hospital

Sault Ste. Marie, Ontario, Canada

Location

Humber River Hospital

Toronto, Ontario, M3M 0B2, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

North York General Hospital

Toronto, Ontario, Canada

Location

St. Joseph's Health Centre

Toronto, Ontario, Canada

Location

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

Location

Jewish General Hospital

Montreal, Quebec, Canada

Location

CHRU Brest

Brest, France

Location

Related Publications (1)

• 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.

  PMID: 36100263 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Tinzaparin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Marc Carrier, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Rebecca Ann Auer, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2011
• First Posted: October 20, 2011
• Study Start: September 1, 2011
• Primary Completion: December 31, 2020
• Study Completion: February 1, 2021
• Last Updated: May 17, 2021

Record last verified: 2021-05

Locations

BE (1); FR (1); CA (14)