ASA in Prevention of Ovarian Cancer (STICs and STONEs)

Study Overview
=================
Brief Summary
-----------------
While ASA is not a cancer medication, research suggests that taking ASA reduces the probability of getting many types of cancer because of its anti-inflammatory action. Inflammation in the ovaries during ovulation is thought to contribute to the development of ovarian cancer, and, because ASA is an anti-inflammatory medication, it may help to prevent it.

Detailed Description
-----------------
The standard or usual treatment for women with a high risk gene mutation, BRCA1 or BRCA2, is to have risk-reducing surgery to remove the fallopian tubes and ovaries (bilateral salpingo-oophorectomy or bilateral salpingectomy inclusive of fimbria) after they have decided not to have more children naturally. Acetylsalicylic Acid (ASA) is a safe, well tolerated drug taken by mouth. ASA has been available for over 100 years and has been used mainly to relieve fever and pain, but also as an anti-inflammatory medication in order to reduce inflammation (swelling).

Official Title
-----------------
A Randomized Phase II Double-Blind Placebo-Controlled Trial of Acetylsalicylic Acid (ASA) in Prevention of Ovarian Cancer in Women With BRCA 1/2 Mutations (STICs and STONEs)

Conditions
-----------------
Ovarian Cancer Prevention

Intervention / Treatment
-----------------
* Drug: Acetylsalicylic acid
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Previously documented germline BRCA1/2 pathogenic mutation or likely pathogenic variant based on the ACMG 2015 guidelines Risk-reducing surgery (bilateral salpingo-oophorectomy or bilateral salpingectomy inclusive of fimbria) scheduled for within 6 months to 2 years after the date of randomization as standard of care, for women who have completed their families ECOG performance status 0 or 1 Age ≥ 18 years old Subject is able (i.e. sufficiently literate) and willing to complete the Credibility/Expectancy questionnaire in English or French. Subject consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each subject must sign a consent form prior to enrollment in the trial to document their willingness to participate Subjects must be accessible for treatment and follow up. Subjects randomized on this trial must be treated and followed at the participating centre. In accordance with CCTG policy, protocol treatment is to begin within 2 working days after subject randomization Women of childbearing potential must have agreed to use a highly effective contraceptive method for the duration of the study treatment and for 30 days post last dose of study medication Exclusion Criteria: Subjects with history of other malignancies, except: adequately treated non-melanoma skin cancer; curatively treated in-situ cancer of the cervix; previously diagnosed (at any point) breast cancer, treated with curative intent; prior chemotherapy is allowed and the last dose must be ≥ 12 months prior to randomization; endocrine therapy for breast cancer is allowed at any time. other solid tumours curatively treated with no evidence of disease for > 5 years. Subjects who have been treated with any PARP-inhibitors (e.g. olaparib) at any time. Subjects with active bleeding or bleeding diathesis. Subjects with active peptic ulcer. Subjects with renal, hepatic or congestive heart failure. Subjects with concurrent use of anti-coagulants and/or anti-platelet agents. Subjects with prior bilateral salpingectomy. Subjects with history of chronic daily use of ASA or NSAIDs. Subjects with intolerance of ASA including subjects with a history of asthma induced by salicylates or substances with a similar action, notably non-steroidal-anti-inflammatory drugs. Ongoing or planned pregnancy. Subjects who are breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acetylsalicylic Acid (ASA)<br> | Drug: Acetylsalicylic acid<br>* 81 mg PO daily or 325 mg PO daily<br>* Other names: ASA;|
| Sham Comparator: Placebo<br> | Other: Placebo<br>* One tablet PO daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of pre- & malignant lesions found during prophylactic risk reduction surgery using a stratified Cochran-Mantel-Haenszel test |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptance of the ASA intervention from the self-report Credibility/Expectancy Questionnaire |  | 5 years | 
| Compliance of taking ASA by serum monitoring |  | 5 years |