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

Plain English Summary

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 is a Phase 3 clinical trial sponsored by Alliance for Clinical Trials in Oncology studying Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Early Stage Breast Carcinoma. This trial compares 6 months vs. 12 months of HER2-targeted therapy for HER2+ breast cancer patients who achieved a pathologic complete response after neoadjuvant chemotherapy with trastuzumab. Eligible patients must have early-stage HER2+ breast cancer, achieved a pathologic complete response after neoadjuvant chemotherapy, and are at least 18 years old. Participants will receive either 6 or 12 months of HER2-targeted therapy, with regular check-ups and tests to monitor their health. Alternative treatments include standard 12 months of HER2-targeted therapy or other adjuvant therapies as recommended by their oncologist. The trial aims to enroll 1524 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible patients must have early-stage HER2+ breast cancer, achieved a pathologic complete response after neoadjuvant chemotherapy, and are at least 18 years old. Patients must have no residual invasive disease in the breast or lymph nodes after neoadjuvant therapy, and must have received at least 12 weeks of trastuzumab and a maximum of 24 weeks of combined neoadjuvant and adjuvant therapy. Participants must not be pregnant, have stage IV breast cancer, or have a prior or concurrent malignancy. Patients must have adequate hepatic, renal, and bone marrow function and must not be using investigational anti-cancer agents. This trial is studying Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Early Stage Breast Carcinoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures, such as recurrence-free survival, will provide valuable insights into the effectiveness of shorter treatment durations, which could impact patient care and treatment guid The specific primary outcome measures are: Recurrence-free survival (RFS) (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) (At 12 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill the treatment gap by potentially reducing the duration of HER2-targeted therapy for HER2+ breast cancer patients who have achieved a pathologic complete response, which could l As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Early Stage Breast Carcinoma, where improved treatment options are needed.

Investor Insight

The market for HER2+ breast cancer treatments is substantial, with a competitive landscape that includes various targeted therapies. The approval probability is high given the clear clinical need and Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1524 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have early-stage HER2+ breast cancer and achieved a pathologic complete response after neoadjuvant chemotherapy with trastuzumab. Participation involves receiving either 6 or 12 months of HER2-targeted therapy, with regular check-ups and tests to monitor your health. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 1,524 participants

Interventions

• BIOLOGICAL: Trastuzumab (Herceptin) — Given IV or SC
• BIOLOGICAL: Pertuzumab — Given IV or SC
• PROCEDURE: Echocardiography — Undergo ECHO
• PROCEDURE: Multigated Acquisition Scan — Undergo MUGA
• PROCEDURE: Mammography — Undergo mammography

Primary Outcomes

• Recurrence-free survival (RFS) (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) (At 12 months)

Secondary Outcomes

• 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)

Full Eligibility Criteria

Inclusion Criteria:

* Patients (females and males) with clinical stage T1c-T3 (or Tx) and nodal stage N0-N1 (except T3N1 tumors, which are not eligible)
* Patients must have no residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy. Residual ductal carcinoma in situ (DCIS) is allowed. Patients with residual isolated tumor cells at surgery are considered node-positive and are not eligible
* HER2+ by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Central pathology review is not required. In cases where there were multiple tumor sites in breast/nodes that had HER2 testing at diagnosis, at least one site must have been HER2+ AND the treating investigator must feel it is in the patient's best interest to be treated as having HER2+ breast cancer
* Known hormone receptor status as defined by ASCO/CAP guidelines. Estrogen receptor (ER) and progesterone receptor (PR) of any values are allowed. Hormone receptor positive status can be determined by either known positive ER or known positive PR status; hormone receptor negative status must be determined by both known negative ER and known negative PR
* If invasive disease was present in both breasts, participation in the study is permitted as long as the eligibility criteria are met for both tumors/breasts (including the requirement that at least one biopsied site on each side must have been HER2+)
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Patients must have received neoadjuvant chemotherapy in combination with trastuzumab with or without pertuzumab for a minimum of 12 weeks. All chemotherapy must have been completed preoperatively

  * Patient must complete a minimum of 12 weeks of coverage with trastuzumab and a maximum of 24 weeks in the combined neoadjuvant and adjuvant setting prior to trial registration. Trastuzumab may have been administered either weekly or once every 3 weeks (q3weeks). (For purposes of this eligibility criterion, a single dose of q3week trastuzumab would provide 3 weeks of coverage; a single dose of once a week (q1week) trastuzumab would provide 1 week of coverage. If a q3week dose of trastuzumab were administered and then the subsequent dose was delayed for any period of time, that would still count as 3 weeks of coverage.)
  * Administration of endocrine therapy for treatment of this breast cancer is allowed prior to trial registration. If a patient received prior breast cancer endocrine therapy (eg tamoxifen or aromatase inhibitor) for DCIS or preventive indication, and endocrine therapy is indicated for treatment of their current breast cancer, then prior endocrine therapy must have been stopped \> 12 months prior to registration on this protocol
  * No use of investigational anti-cancer agents at time of registration
* Patient must register within 14 weeks of final surgery
* Adequate excision: Surgical removal of all clinically evident disease in the breast and lymph nodes as follows:

  * Breast surgery: Total mastectomy with grossly negative margins (in the opinion of the surgeon there is no disease grossly at the margins) or breast-conserving surgery with histologically negative margins (no ink on tumor, including DCIS) unless those margins are anterior at the skin or posterior at the chest wall and no additional margin re-excision can be performed
  * Lymph node surgery: Lymph node surgery must have been performed and can include sentinel lymph node biopsy, targeted axillary dissection, or axillary dissection, at the discretion of the breast surgeon
* Adequate radiation: Patients who completed breast-conserving surgery (i.e. lumpectomy) must have received or plan to receive adjuvant radiation. If breast-conserving surgery was performed but patient will not be receiving breast radiation, the patient is not eligible. Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation) are not eligible

  * Adjuvant radiation can be given on study, and in this case is encouraged to be given concurrently with adjuvant HER2-directed therapy, per investigator discretion
  * Targeting of the regional nodal basins will be at treating investigator discretion
* Not pregnant and not nursing, because this study involves agents with known teratogenic potential. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test should be performed prior to receiving HER2-directed therapy according to local standard practice
* Adequate hepatic, renal and bone marrow function to receive adjuvant HER2-directed therapy in the opinion of the treating investigator. There are no specific required laboratory values for eligibility
* No stage IV (metastatic) breast cancer
* Patients with a prior or concurrent malignancy whose natural history or treatme

Trial Locations

• Cancer Center at Saint Joseph's, Phoenix, Arizona, United States
• Mercy Hospital Fort Smith, Fort Smith, Arkansas, United States
• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro, Jonesboro, Arkansas, United States
• CARTI Cancer Center, Little Rock, Arkansas, United States
• Mission Hope Medical Oncology - Arroyo Grande, Arroyo Grande, California, United States
• Tower Cancer Research Foundation, Beverly Hills, California, United States
• Mercy Cancer Center - Carmichael, Carmichael, California, United States
• Mercy San Juan Medical Center, Carmichael, California, United States
• Enloe Medical Center, Chico, California, United States
• Kaiser Permanente Dublin, Dublin, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Anatomic Stage I Breast Cancer AJCC v8
• Anatomic Stage II Breast Cancer AJCC v8
• Early Stage Breast Carcinoma
• HER2+ Breast Cancer
• Pathologic Complete Response
• Neoadjuvant Chemotherapy
• Trastuzumab
• Pertuzumab
• Pathologic Complete Response (pCR)

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