Pancreatic Cancer, Venous Thromboembolism
Conditions
Keywords
Pancreas, Primary venous thromboembolism, VTE, Chemotherapy, Deep venous thrombosis, Pulmonary embolism, Dalteparin, Fragmin, Thromboprophylaxis
Brief summary
The goal of this clinical research study is to learn if dalteparin can lower the risk of VTE occurring in the legs and lungs. This will be tested in patients with pancreatic cancer who are going to receive chemotherapy. Some patients will receive dalteparin and some will receive no study drug. The safety of dalteparin will also be studied.
Detailed description
Study Drug: Dalteparin is designed to thin the blood and block blood from clotting. This may lower the risk of VTE. Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) into 1 of 2 groups. There is an equal chance of being assigned to either group. Group 1 will receive dalteparin. Group 2 will not receive a study drug. During this study, all study participants will be routinely checked for VTE by ultrasounds and CT scans. You may also receive standard therapies for preventing VTE. This may include blood-thinning drugs while you are in the hospital, getting up and moving around at least 5 times per day, and/or wearing special stockings or boot-like devices designed to put pressure on the feet. Genetic Research Testing: Before starting your therapy (at baseline), blood (about 1 teaspoon) will be drawn and stored for genetic testing. Researchers want to use DNA (the genetic material in cells) to look for markers that may be related to having a high risk for developing blood clots. The samples will be processed and stored at MD Anderson. Once this study ends, the DNA will be tested further in Dr. Futreal's laboratory and/or may be shipped outside to Illumina Sequencing Services (San Diego, CA) for genetic research. The samples will be deidentified before shipping. Before your samples are sent to the outside laboratory for banking, your name and any personal identifying information will be coded to protect your privacy. The outside researchers will not have access to the codes that link the samples to your identity. Study Drug Administration: If you are in Group 1, you will receive dalteparin by injection under your skin, once a day for 16 weeks. You and/or your caregiver will be taught how to perform injections. Study Visits: At every study visit, the following tests and procedures will be performed: * You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature and breathing rate). * Your medical history will be recorded. About every 2 weeks after chemotherapy starts until Week 16, blood (about 2 teaspoons) will be drawn for routine tests. This test may be repeated more often if the doctor decides it is needed. Before each new cycle of chemotherapy during Weeks 1-16, blood (about 2 teaspoons) will be drawn for routine tests to check the function of your liver and kidneys. At Weeks 8 and 16 (+/- 7 days), the following procedures will be performed: * You will have an ultrasound of your legs to check for blood clots. * If the doctor decides it is needed, you will have CT scans to check the status of the cancer. Researchers will also check your chest CT scans to look for blood clots in the lungs. Length of Study Participation: You may remain on study for up to 16 weeks. You will be taken off study early if blood clots occur or you experience intolerable side effects. Follow-Up Phone Calls: This study has a 3-year follow-up period. In Year 1, you will receive a follow-up phone call from the study staff in the first month and then at Months 3, 6, 9, and 12. In Years 2 and 3, you will be called every 6 months. The study staff will ask about your overall health. In the first phone call, you will also be asked about any side effects that may have occurred. This is an investigational study. Dalteparin is commercially available and FDA approved for use in preventing VTE that may occur for other reasons. Those reasons include abdominal surgery; surgery for a hip fracture, hip replacement, or knee replacement; and illnesses causing patients to be unable to move around. Dalteparin is also commercially available and FDA approved to treat VTE in cancer patients. However, it is investigational to use dalteparin to prevent VTE in cancer patients receiving chemotherapy. Up to 87 patients will take part in this study. All will be enrolled at MD Anderson.
Interventions
DRUGDalteparin
5000 units subcutaneous, by injection under the skin, daily for 16 weeks
Sponsors
Eisai Inc.
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with the diagnosis of advanced stage (unresectable or metastatic) adenocarinoma of the pancreas. Patients with borderline resectable will also be eligible if they are starting chemotherapy and/or chemo/radiation therapy (RT) prior to attempting resection. 2. Patients must be planning to initiate systemic chemotherapy within 2 weeks. Chemotherapy that is being given concurrently with radiation is allowed. 3. Age \>/= 18 years old 4. Adequate renal function defined as a calculated creatinine clearance of \> 50 mL/min (as reported by the MDACC laboratory using MDRD method or using Cockroft and Gault formula). 5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. 6. Negative urine or serum pregnancy test in women with childbearing potential, within one week prior to initiation of treatment. 7. Patients must sign an Informed Consent. 8. Patient must agree to transfusion of blood products, when indicated. 9. Ability to administer subcutaneous injections of the study drug by the patient and/or care giver.
Exclusion criteria
1. Patients with evidence of venous thrombosis on the initial lower extremity screening ultrasound or incidental VTE of other sites (e.g. PE, Abdominal/pelvic vein thrombosis, etc.). 2. Patients already taking prophylactic or full dose anticoagulation (eg. heparin, low-molecular weight heparin, fondaparinux, or coumadin). 3. Patients with currently active bleeding. 4. The presence of a condition with a high risk for bleeding, including but not limited to active peptic ulcer, recent neurosurgery, or cirrhosis with esophageal varices. 5. Patients with known brain metastases. 6. Patients with a known bleeding diathesis. 7. Patients with a platelet count \< 50,000. 8. Patients with known hypersensitivity to dalteparin. 9. Patients who regularly use medications known to increase the risk of bleeding such as \>/= 325 mg of aspirin daily, or daily clopidogrel, or daily non-steroidal antiinflammatory medications (eg., ibuprofen, naproxen).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Venous Thromboembolic Events (VTE) | 16 weeks of treatment | Venous thromboembolism (VTE) defined by both symptomatic and asymptomatic VTE which includes deep venous thrombosis (DVT) and pulmonary embolism (PE) through clinical assessments and radiologic studies. All patients undergo bilateral lower extremity ultrasound every 2 months while on study (total of 3 exams including pre-randomization). VTE requires imaging documentation to evaluate use of prophylactic anticoagulation in reducing the occurrence of VTE in a patient population with a known high risk of VTE. |
Countries
United States
Participant flow
Recruitment details
Recruitment period: April 06, 2010 to August 23, 2012. All recruitment done at the University of Texas (UT) MD Anderson Cancer Center.
Pre-assignment details
Of the 87 participants enrolled on the study, only 75 were randomized. Twelve enrolling participants were screen failures or withdrew before randomization thus were excluded before assignments to groups.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Dalteparin Dalteparin 5000 units subcutaneous, by injection under the skin, daily for 16 weeks. | 38 |
| Group 2: Control No Dalteparin study drug. | 37 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Ineligible | 1 | 3 |
| Overall Study | Treatment Plan Changed | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Group 1: Dalteparin | Group 2: Control | Total |
|---|---|---|---|
| Age, Continuous | 59 years | 64 years | 61.5 years |
| Age, Customized <60 | 21 years | 10 years | 31 years |
| Age, Customized >=60 | 17 years | 27 years | 44 years |
| Race/Ethnicity, Customized Black or African American | 3 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized Causacian | 31 participants | 31 participants | 62 participants |
| Race/Ethnicity, Customized Hispanic | 2 participants | 3 participants | 5 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Unknown or Unreported | 1 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 38 participants | 37 participants | 75 participants |
| Sex: Female, Male Female | 18 Participants | 16 Participants | 34 Participants |
| Sex: Female, Male Male | 20 Participants | 21 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 34 | 33 / 33 |
| serious Total, serious adverse events | 34 / 34 | 33 / 33 |
Outcome results
Primary
Number of Participants With Venous Thromboembolic Events (VTE)
Venous thromboembolism (VTE) defined by both symptomatic and asymptomatic VTE which includes deep venous thrombosis (DVT) and pulmonary embolism (PE) through clinical assessments and radiologic studies. All patients undergo bilateral lower extremity ultrasound every 2 months while on study (total of 3 exams including pre-randomization). VTE requires imaging documentation to evaluate use of prophylactic anticoagulation in reducing the occurrence of VTE in a patient population with a known high risk of VTE.
Time frame: 16 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Dalteparin | Number of Participants With Venous Thromboembolic Events (VTE) | 2 participants |
| Group 2: Control | Number of Participants With Venous Thromboembolic Events (VTE) | 9 participants |