Ovarian Cancer, Venous Thromboembolism
Conditions
Brief summary
This is a pilot study to determine the safety and efficacy of low dose aspirin for the prevention of venous thromboembolism among women with advanced ovarian cancer receiving neoadjuvant chemotherapy.
Detailed description
Subjects who are receiving neoadjuvant chemotherapy for advanced epithelial ovarian cancer, including primaries of mullerian, peritoneal, or fallopian tube origin, with a Khorana score of 1 will be recruited from the Duke Gynecology Oncology clinic at Duke Cancer Institute. After discussion of the risks and benefits, written informed consent will be obtained for initiation of prophylactic, daily low dose aspirin (81 mg) therapy. Subjects will receive aspirin tablets in medication vials obtained from the Duke pharmacy supply and will be instructed to take one tablet daily until the day of their interval debulking surgery. The primary outcomes will be safety and medication adherence. Secondary outcome will be rate of VTE. We hypothesize that daily low dose aspirin will be safe with acceptable medication adherence and may reduce the incidence of venous thromboembolic events during neoadjuvant chemotherapy for low risk patients when compared to a historical control. Adverse safety events and medication adherence will be evaluated using descriptive statistics using a validated questionnaire. We will calculate the incidence of venous thromboembolism among the study cohort and estimate a 95% exact binomial confidence interval. A drop greater than 20% (from 8% in the historical control to 6.4%) in the venous thromboembolism rate would be considered clinically meaningful. We will also monitor for adverse safety events related to low dose aspirin use, including major or minor bleeding events, clinically significant thrombocytopenia (resulting in treatment delay), and gastrointestinal complications. Of note, low dose aspirin for venous thromboembolism prevention is already considered an acceptable option for standard of care for patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone as well as for postoperative thromboprophylaxis for some orthopedic procedures; we therefore believe the potential benefit outweighs any clinically significant risks. Subjects will be recruited from patients at the Duke Gynecology Oncology clinics at the Duke Cancer Center or Macon Pond (Duke Women's Cancer Care Raleigh) with advanced epithelial ovarian cancer, including primaries of mullerian, peritoneal, or fallopian tube origin, who are going to initiate neoadjuvant chemotherapy. A provider will approach the patient and inquire about interest in participating in the study. If the patient desires to receive more information about participating, clinical research personnel will discuss the study with patient and obtain informed consent if all selection criteria are met (detailed in a prior section). If the patient consents, they will then be considered an enrolled study subject. We will use the Duke hosted REDCap platform for collecting eConsent. If the patient is willing to hear about the study but a member of the research team is unable to be physically present in clinic, the research team will contact the patient via phone to perform the same recruitment, eligibility screening, and consent process that would typically be completed in person. An estimated 120 patients will receive neoadjuvant chemotherapy for advanced ovarian cancer at Duke Gynecology Oncology clinics for the designated study recruitment period of 07/01/2020 to 12/30/2021 with an estimated 50% accrual rate for a total of 60 enrolled patients. Currently there is no established practice guideline for venous thromboembolism prophylaxis for these high risk patients. There will be no direct cost to subjects for participation in the study. They will not incur any costs for travel as they will already be presenting to Duke Gynecology Oncology clinic for their scheduled clinic visit. The study drug will be provided without cost. There will be additional time (10 minutes) incurred with study participation for informed consent and explanation of the study design and medication adherence diary. Subjects will not be compensated.
Interventions
DRUGAspirin
81 mg aspirin daily
Sponsors
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Khorana score = 1 * Over age 18 * English-speaking female patients * Able to consent * Receiving neoadjuvant chemotherapy Cancer of primary ovarian, fallopian tube, mullerian, or peritoneal origin
Exclusion criteria
* Allergy or intolerance to study medication * Indication for a non-aspirin form of antiplatelet (i.e. cardiac stent) * Already on alternative form of anticoagulation * Active bleeding * High risk for active bleeding (i.e. recent intracranial bleed or gastrointestinal bleed, known brain metastases) * Thrombocytopenia (platelets \<50,000) * Unable to complete medication adherence diary * Unable to take oral medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing a Venous Thromboembolism | Up to six months | — |
| Number of Participants With at Least One Adverse Event | Up to six months | Adverse events will only include those that are determined to be related to the study drug. |
| Medication Adherence | Up to six months | Patient adherence to aspirin as defined by percent of pills used. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aspirin Patients with a Khorana risk score of 1 receive 81 mg aspirin daily while receiving neoadjuvant chemotherapy for ovarian cancer.
Aspirin: 81 mg aspirin daily | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Aspirin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 70 years STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 19 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 19 |
| other Total, other adverse events | 0 / 19 |
| serious Total, serious adverse events | 6 / 19 |
Outcome results
Primary
Medication Adherence
Patient adherence to aspirin as defined by percent of pills used.
Time frame: Up to six months
Population: Data not collected.
Primary
Number of Participants Experiencing a Venous Thromboembolism
Time frame: Up to six months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants Experiencing a Venous Thromboembolism | 4 Participants |
Primary
Number of Participants With at Least One Adverse Event
Adverse events will only include those that are determined to be related to the study drug.
Time frame: Up to six months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With at Least One Adverse Event | 0 Participants |