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Aspirin in Preventing Recurrence of Cancer in Patients With HER2 Negative Stage II-III Breast Cancer After Chemotherapy, Surgery, and/or Radiation Therapy

A Randomized Phase III Double Blinded Placebo Controlled Trial of Aspirin as Adjuvant Therapy for HER2 Negative Breast Cancer: The ABC Trial

Status
Terminated
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02927249
Enrollment
3021
Registered
2016-10-07
Start date
2017-01-06
Completion date
2023-02-15
Last updated
2026-09-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Node Positive HER2 Negative Breast Cancer

Brief summary

This randomized phase III trial studies how well aspirin works in preventing the cancer from coming back (recurrence) in patients with human epidermal growth factor receptor 2 (HER2) negative breast cancer after chemotherapy, surgery, and/or radiation therapy. Aspirin is a drug that reduces pain, fever, inflammation, and blood clotting. It is also being studied in cancer prevention. Giving aspirin may reduce the rate of cancer recurrence in patients with breast cancer.

Detailed description

This is a randomized double-blind placebo-controlled phase III trial of aspirin (300 mg daily) in early stage node-positive HER2 negative breast cancer patients. Patients will be randomized 1:1 within stratum defined by: Hormone Receptor status (HR positive vs HR negative), body mass index (\<30 vs ≥ 30 kg/m2) and stage (Stage II vs III). The primary objective of this trial is to compare the effect of aspirin versus placebo upon invasive disease free survival (iDFS). Primary objective To compare the effect of aspirin (300 mg daily) versus placebo upon invasive disease free survival (iDFS) in early stage node-positive HER2 negative breast cancer patients. Secondary objectives 1. To compare the effect of aspirin versus placebo in early stage node-positive HER2 negative breast cancer patients upon: 1. Distant disease-free survival 2. Overall survival 3. Cardiovascular disease (see Section11.3) 2. To compare the toxicity of aspirin versus placebo in early stage node-positive HER2 negative breast cancer patients. 3. To assess adherence to aspirin and placebo among early stage node-positive HER2 negative breast cancer patients. 4. To bank tumor and germline deoxyribonucleic acid (DNA), plasma and urine collected at baseline and sequential plasma and urine collected 2 years later for future measurement of inflammatory markers. 5. To determine if there are subgroups of participants characterized by lifestyle factors associates with greater inflammation for whom there is greater benefit of aspirin versus placebo upon iDFS. Patients are followed up to 10 years after study enrollment.

Interventions

OTHERPlacebo

Given PO

DRUGAspirin

Given PO

Sponsors

Alliance for Clinical Trials in Oncology
Lead SponsorOTHER
National Cancer Institute (NCI)
CollaboratorNIH
United States Department of Defense
CollaboratorFED
Bayer
CollaboratorINDUSTRY
Canadian Cancer Trials Group
CollaboratorNETWORK

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No

Inclusion criteria

* Histologic documentation of women or men with node positive, HER2 negative, anatomic stage II or III breast carcinoma and high risk node negative (defined as estrogen receptor \[ER\] and progesterone receptor \[PR\] negative and tumor size \> 2 cm) within one year of diagnosis and free of recurrence; patients with pN1mic are eligible; if neoadjuvant therapy was received, either initial clinical stage (determined by physical and or radiologic examination) or post-operative pathologic stage can be used for eligibility purposes, with the higher stage determining eligibility; histologic documentation of node positivity is required; bilateral breast cancers are allowed, as long as both cancers are HER2 negative and at least one of the cancers meets eligibility * Any ER/progesterone receptor (PgR) status allowed * Prior adjuvant treatment with chemotherapy and/or endocrine therapy, as determined by the treating physician, is allowed; the last dose of chemotherapy or radiation therapy must be at least 30 days prior to study registration; concurrent hormonal therapy will be allowed * Regular nonsteroidal anti-inflammatory drug (NSAID)/aspirin use at any dose (including baby aspirin) (defined as \>= 5 days per week) is allowed if aspirin and/or NSAIDs are stopped for 30 days prior to study entry and throughout the study period; participants will be encouraged to use acetaminophen for minor pain and fever * Patients must be enrolled within 1 year after diagnosis * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Patients with a prior history of gastric/duodenal ulcers documented on endoscopy can be enrolled as long as the ulcers did not cause bleeding requiring a blood transfusion/major intervention; for patients who are Helicobacter pylori positive, a course of Helicobacter pylori eradication treatment must have been completed * No history of gastrointestinal bleeding (GI) bleeding requiring a blood transfusion, endoscopic or operative intervention * No history of any prior stroke (hemorrhagic or ischemic) * No concurrent anticoagulation with warfarin or heparin/heparin analogues, clopidogrel, oral direct thrombin inhibitors, or direct factor XA inhibitors * No history of atrial fibrillation or myocardial infarction * No history of grade 4 hypertension, defined as hypertension resulting in life-threatening consequences (e.g., malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis) * No chronic (duration \> 30 days) daily use of oral steroids * No known allergy to aspirin * No prior malignancy of any type (including ductal breast carcinoma in situ \[DCIS\]) within the past 5 years except for current diagnosis of breast cancer, and any prior diagnosis of basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; patients with a prior history of breast cancer greater than 5 years from study screening may participate in this study * Concurrent enrollment on a non-chemotherapy treatment trial will be allowed, as long as that trial allows concurrent daily aspirin use

Design outcomes

Primary

MeasureTime frameDescription
Median Invasive Disease-free Survival (iDFS)5 yearsInvasive disease-free survival (iDFS), is defined as time from randomization to the first occurrence of any one of the following events for invasive disease: Distant recurrence, locoregional recurrence, ipsilateral or contralateral breast cancer, second primary (non-breast) invasive cancer or death from any cause. Censoring will occur on the date the patient was last known to be alive and free from all invasive breast cancer and second invasive primaries.

Secondary

MeasureTime frameDescription
Incidence of Toxicities, Graded Using the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.35 yearsThe count of patients that experianced at least one grade 3 or higher adverse event, regardless of the attribution to study drug.
Median Overall Survival (OS)5 yearsOverall survival (OS) is defined as the time from randomization to death from any cause; surviving patients will be censored at the date last known to be alive.
Incidence of Cardiovascular Disease (Including Cerebrovascular Events, Myocardial Infarction, or Coronary Artery Disease Requiring Stent Placement, Angioplasty, or Bypass Surgery)5 yearsThe count of patients with cardiovascular disease by arm.
Median Distant Disease Free Survival (DDFS)5 yearsDDFS is defined as the time from randomization to the first occurrence of any one of the following events for invasive disease: Distant recurrence, second primary (non-breast) invasive cancer or death from any cause; censoring will occur at the date the patient was last known to be alive and free from distant invasive breast cancer and second invasive primaries.

Countries

Canada, Guam, Puerto Rico, United States

Contacts

STUDY_CHAIRWendy Chen, M.D., MPH

Dana-Farber Cancer Institute

Participant flow

Participants by arm

ArmCount
Arm I (Aspirin)
Patients receive aspirin PO QD for five years in the absence of disease progression or unacceptable toxicity.
1,511
Arm II (Placebo)
Patients receive placebo PO QD for five years in the absence of disease progression or unacceptable toxicity.
1,510
Total3,021

Baseline characteristics

CharacteristicArm II (Placebo)TotalArm I (Aspirin)
Age, Continuous52 years53 years53 years
Ethnicity (NIH/OMB)
Hispanic or Latino
113 Participants225 Participants112 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
1351 Participants2719 Participants1368 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
46 Participants77 Participants31 Participants
Race (NIH/OMB)
American Indian or Alaska Native
17 Participants25 Participants8 Participants
Race (NIH/OMB)
Asian
55 Participants121 Participants66 Participants
Race (NIH/OMB)
Black or African American
139 Participants279 Participants140 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
7 Participants13 Participants6 Participants
Race (NIH/OMB)
Unknown or Not Reported
61 Participants112 Participants51 Participants
Race (NIH/OMB)
White
1231 Participants2471 Participants1240 Participants
Sex: Female, Male
Female
1503 Participants3005 Participants1502 Participants
Sex: Female, Male
Male
7 Participants16 Participants9 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
48 / 1,51143 / 1,510
other
Total, other adverse events
621 / 1,393726 / 1,415
serious
Total, serious adverse events
99 / 1,39391 / 1,415

Outcome results

Primary

Median Invasive Disease-free Survival (iDFS)

Invasive disease-free survival (iDFS), is defined as time from randomization to the first occurrence of any one of the following events for invasive disease: Distant recurrence, locoregional recurrence, ipsilateral or contralateral breast cancer, second primary (non-breast) invasive cancer or death from any cause. Censoring will occur on the date the patient was last known to be alive and free from all invasive breast cancer and second invasive primaries.

Time frame: 5 years

ArmMeasureValue (MEDIAN)
Arm I (Aspirin)Median Invasive Disease-free Survival (iDFS)NA Months
Arm II (Placebo)Median Invasive Disease-free Survival (iDFS)NA Months
95% CI: [0.91, 1.56]
Secondary

Incidence of Cardiovascular Disease (Including Cerebrovascular Events, Myocardial Infarction, or Coronary Artery Disease Requiring Stent Placement, Angioplasty, or Bypass Surgery)

Time frame: Up to 5 years

Secondary

Incidence of Toxicities, Graded Using the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.3

Time frame: Up to 5 years

Secondary

Median Distant Disease Free Survival (DDFS)

DDFS is defined as the time from randomization to the first occurrence of any one of the following events for invasive disease: Distant recurrence, second primary (non-breast) invasive cancer or death from any cause; censoring will occur at the date the patient was last known to be alive and free from distant invasive breast cancer and second invasive primaries.

Time frame: 5 years

ArmMeasureValue (MEDIAN)
Arm I (Aspirin)Median Distant Disease Free Survival (DDFS)NA Months
Arm II (Placebo)Median Distant Disease Free Survival (DDFS)NA Months
95% CI: [0.83, 1.52]
Secondary

Median Overall Survival (OS)

Overall survival (OS) is defined as the time from randomization to death from any cause; surviving patients will be censored at the date last known to be alive.

Time frame: 5 years

ArmMeasureValue (MEDIAN)
Arm I (Aspirin)Median Overall Survival (OS)NA Months
Arm II (Placebo)Median Overall Survival (OS)NA Months
95% CI: [0.74, 1.69]

Source: ClinicalTrials.gov · Data processed: Sep 5, 2026