Clinical trial NCT03480776: ASA in Prevention of Ovarian Cancer (STICs and STONEs)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Ovarian Cancer Prevention
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Apotex Inc.
First posted: 2018-03-29
Enrollment: 117
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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.

Primary outcomes:
measure: Proportion of pre- & malignant lesions found during prophylactic risk reduction surgery using a stratified Cochran-Mantel-Haenszel test
timeFrame: 5 years
Secondary outcomes:
measure: Acceptance of the ASA intervention from the self-report Credibility/Expectancy Questionnaire
timeFrame: 5 years
measure: Compliance of taking ASA by serum monitoring
timeFrame: 5 years
Other outcomes:
measure: Compliance of taking ASA by evaluation of treatment completion rates
timeFrame: 5 years
measure: Compliance of taking ASA by reasons for early discontinuation of protocol intervention.
timeFrame: 5 years
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Peter McCallum Cancer Institute
state: Victoria
city: Subiaco
country: Australia
facility: King Edward Memorial Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St John of God Subiaco
state: Western Australia
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: Clinical Research Unit at Vancouver Coastal
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: St. John's
country: Canada
facility: Dr. H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: North York General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Women's College Hospital
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de l'Est-de-I'lle-de-Montreal
state: Quebec
city: Montreal
country: Canada
facility: CHUM-Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: Hotel-Dieu de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie - Centre hospitalier
state: Quebec
Study officials:
affiliation: Univ. Health Network-OCI/Princess Margaret Hospital, Toronto, ON Canada
name: Amit Oza
role: STUDY_CHAIR
affiliation: Univ. Health Network-OCI/Princess Margaret Hospital, Toronto, ON Canada
name: Stephanie Lheureux
role: STUDY_CHAIR
References: