NCT06876714|RecruitingPhase 3

ShortStop-HER2: 12 Months vs. 6 Months of HER2-targeted Medications for People With HER2+ Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Trastuzumab

ShortStop-HER2: Shortened Duration of Adjuvant Therapy in Patients With Early-Stage HER2+ Breast Cancer Who Achieve pCR After Neoadjuvant Chemotherapy With HER2 Blockade

Alliance for Clinical Trials in Oncology ClinicalTrials.gov

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2 other identifiers

A012303NCI-2024-10478

Study Type

interventional

Target

1,524

Locations

2 countries

Sites

487

Timeline

RegisteredMar 2025

StartedSep 2025

CompletionMar 2037

Brief Summary

This phase III trial compares 6 months of human epidermal growth factor receptor 2 (HER2)-targeted therapy to 12 months of HER2-targeted therapy for the treatment of HER2-positive (+) breast cancer in patients that had a pathologic complete response (pCR) after preoperative (neoadjuvant) chemotherapy with trastuzumab. Trastuzumab and pertuzumab are monoclonal antibodies and forms of targeted therapy that attach to a receptor protein called HER2. HER2 is found on some cancer cells. When trastuzumab or pertuzumab attach to HER2, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving 6 months of HER2-targeted therapy may work better than giving 12 months for the treatment of HER2+ breast cancer in patients that had a pCR after neoadjuvant chemotherapy with trastuzumab.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

1,524

participants targeted

Target at P75+ for phase_3

Timeline

133mo left

Started Sep 2025

Longer than P75 for phase_3

Geographic Reach

2 countries

487 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

11.5 years study duration

Study Progress5%

Sep 2025Mar 2037

First Submitted

Initial submission to the registry

March 10, 2025

Completed

4 days until next milestone

First Posted

Study publicly available on registry

March 14, 2025

Completed

6 months until next milestone

Study Start

First participant enrolled

September 17, 2025

Completed

2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 13, 2028

Expected

9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 13, 2037

Last Updated

February 4, 2026

Status Verified

February 1, 2026

Enrollment Period

2.5 years

First QC Date

March 10, 2025

Last Update Submit

February 3, 2026

Conditions

Anatomic Stage I Breast Cancer AJCC v8 Anatomic Stage II Breast Cancer AJCC v8 Early Stage Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

Recurrence-free survival (RFS)
The Kaplan-Meier method will be used to estimate the distribution of RFS times and a stratified log-rank test for non-inferiority will be used to assess whether RFS with 6 total months of human epidermal growth factor receptor 2 (HER2)-blockade is non-inferior to standard-of-care 12 total months of HER2-blockade in this patient population. Stratified Cox modeling will be used to estimate the hazard ratio and corresponding one-sided 95% confidence interval (CI).
From randomization to invasive local, regional or distant breast cancer recurrence, or death from any cause prior to a documented disease recurrence, assessed up to 10 years
Functional Assessment of Cancer Therapy-Breast (FACT-B) total score (Quality of life)
Will compare the FACT-B total score between patients randomized to receive 6 months versus 12 months of combined neoadjuvant/adjuvant HER2 blockade. All questionnaires will be scored according to published scoring algorithms, including recommendations for addressing missing items within a scale. An intention-to-treat (ITT) approach will be used for all analyses. All statistical tests will be 2-sided, and p-values \< 0.05 will be considered statistically significant. To evaluate the between-arm mean difference in scores, a repeated measures mixed model will be estimated based on FACT-B total scores at all time points.
At 12 months

Secondary Outcomes (8)

Incidence of grade 3 or higher adverse events (AE)
Baseline to 30 days after last dose of study treatment
Locoregional recurrence (LRR)
From randomization until invasive tumor recurs in the ipsilateral breast or chest wall, axillary, supraclavicular, or internal mammary nodes (if before or synchronous with a systemic recurrence), whichever comes first, assessed up to 10 years
Overall survival
From randomization until death due to any cause, assessed up to 10 years
RFS for key subgroups
From randomization to invasive local, regional or distant breast cancer recurrence, or death from any cause prior to a documented disease recurrence, assessed up to 10 years
Time to central nervous system (CNS) recurrence
up to 10 years
+3 more secondary outcomes

Study Arms (2)

Arm 1 (12-month adjuvant therapy)

ACTIVE COMPARATOR

Patients receive trastuzumab IV or SC on day 1 of each cycle. Patients may also receive pertuzumab IV or SC, at the discretion of the treating investigator, on day 1 of each cycle. Cycles repeat every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA as well as mammography, ultrasound, or MRI throughout the trial. Patients may also optionally undergo blood and tissue sample collection throughout the trial.

Biological: Trastuzumab (Herceptin)Biological: PertuzumabProcedure: EchocardiographyProcedure: Multigated Acquisition ScanProcedure: MammographyProcedure: UltrasoundProcedure: Magnetic Resonance ImagingProcedure: Biospecimen CollectionOther: Questionnaire Administration

Arm 2 (6-month adjuvant therapy)

EXPERIMENTAL

Patients receive trastuzumab IV or SC on day 1 of each cycle. Patients may also receive pertuzumab IV or SC, at the discretion of the treating investigator, on day 1 of each cycle. Cycles repeat every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA as well as mammography, ultrasound, or MRI throughout the trial. Patients may also optionally undergo blood and tissue sample collection throughout the trial.