Radiotherapy Optimization for Low-Risk HER2-Positive Breast Cancer

What is the Purpose of this Study?

This study focuses on individuals who have low-risk HER2-positive breast cancer, which is a type of breast cancer that tests positive for the human epidermal growth factor receptor 2. The purpose of the study is to compare the usual treatment (breast radiation and HER2-targeted drugs after surgery and chemotherapy) to using HER2-targeted drugs alone after surgery and chemotherapy. Researchers aim to determine whether HER2-targeted therapy alone can help prevent the patient’s breast cancer from returning compared to breast radiation and HER2-targeted therapy. Participants will be randomly assigned to one of two study groups and will join the study after they have undergone chemotherapy, HER2-targeted therapy, and surgery. Patients in Group 1 will receive the usual treatment of breast radiation therapy and HER2-targeted therapy after surgery, chemotherapy, and HER2-targeted therapy. Patients in Group 2 will receive only HER2-targeted therapy after surgery, chemotherapy and HER2-targeted therapy.

Eligibility

* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
* female and male patients who have undergone breast conserving surgery and completed a minimum of 4 cycles (12 weeks) of neoadjuvant or adjuvant chemotherapy in combination with HER2-targeted therapy.
-≥ 40 years of age

Inclusion Criteria:

* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.
* female and male patients who have undergone breast conserving surgery and completed a minimum of 4 cycles (12 weeks) of neoadjuvant or adjuvant chemotherapy in combination with HER2-targeted therapy.
-≥ 40 years of age
* ECOG performance status of 0 ,1, or 2/Karnofsky performance status above 60
* Histologically or cytologically confirmed invasive breast carcinoma.
* tumor must have been determined to be HER2-positive by current ASCO/CAP guidelines based on local testing results.
* Patient must have undergone axillary staging, either sentinel node biopsy (SNB) or axillary lymph nodal dissection (ALND). In neoadjuvant patients, SNB following neoadjuvant therapy is strongly recommended. SNB prior to neoadjuvant therapy is discouraged, but patients are permitted if node negative (pN0).
* The following staging criteria must be met according to AJCC 8th edition criteria:
Adjuvant cohort : By pathologic evaluation, the patient's primary tumor must be \
Neoadjuvant cohort: Prior to neoadjuvant therapy, the patient's primary tumor must be \< 3 cm by imaging studies, with negative axillary nodes (cN0) based on axillary U/S, CT, PET or MRI. Physical examination is not sufficient documentation of cN0 status; • Must be ypT0N0 at surgery (lumpectomy); patients with residual non-invasive disease (DCIS) in the surgical specimen (ypTis), are NOT eligible.
* For the Adjuvant cohort, adjuvant therapy must have consisted of a minimum of 4 cycles (12 weeks) of chemotherapy in combination with HER2-targeted therapy.
* For the Neoadjuvant cohort, neoadjuvant therapy must have consisted of a minimum of 4 cycles (12 weeks) of chemotherapy in combination with HER2-targeted therapy.- ; Patients who did not receive chemotherapy in the neoadjuvant setting are not eligible, even if they achieved pCR with their preoperative treatment; nor would these patients become eligible by receiving chemotherapy after surgery.
* In patients assigned to radiation therapy, treatment should start ≤ 12 weeks from surgery on the Neoadjuvant cohort and ≤ 8 weeks from the completion of chemotherapy on the Adjuvant cohort. Patients should continue HER2-targeted therapy during assigned study treatment (radiation or observation).
* Bilateral mammogram or MRI within 52 weeks prior to randomization.
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.

Exclusion Criteria:

* Definitive clinical or radiologic evidence of metastatic disease.
* On the Adjuvant cohort, patients with a primary tumor \>2 cm on pathologic examination of the surgical specimen. On the Neoadjuvant cohort, patients with a primary tumor \> 3 cm or with abnormal or suspicious ipsilateral axillary nodes by pretreatment imaging, unless demonstrated to be negative by cytologic or histologic examination.
* Pathologically positive axillary nodes at any time including of pN0(i+) or pN0(mol+) ypN0(i+) or ypN0(mol+) disease.
* Patient planning for or status-post mastectomy.
* Radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary lymph nodes, unless there is histological confirmation that these nodes are negative for metastatic disease.
* Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast), or mass or non-mass enhancement on MRI (if performed) aside from the known cancer, unless biopsied and found to be benign.
* Non-epithelial breast malignancies such as sarcoma or lymphoma.
* Multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by \> 4 centimeters. If multifocal, all foci should be confined to a maximum tumor bed of 3 cm determined by pathological assessment.
* Paget's disease of the nipple.
* Synchronous (unilateral or bilateral) invasive breast cancer or DCIS. (Patients with synchronous and/or previous contralateral LCIS are eligible.)
* On the Adjuvant cohort, surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re-excision, the patient is eligible).
* Treatment plan that includes regional nodal irradiation.
* Patients treated for a prior invasive breast malignancy are excluded. Contralateral DCIS ≥ 10 years prior to enrollment is permissible.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible unless discontinued prior to randomization.
* Prior ipsilateral breast or thoracic RT for any condition (contralateral RT for DCIS ≥ 10 years prior to randomization is permitted).
* Active collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active systemic lupus erythematosus, or scleroderma.
* Clinicians should consider whether any conditions would make this protocol unreasonably hazardous for the patient.
* Pregnancy or lactation at the time of randomization or intention to become pregnant during treatment. (Note: Pregnancy testing according to institutional standards for patients of childbearing potential must be performed within 14 days prior to randomization.)
* Use of any investigational product within 30 days prior to randomization.

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Where can I participate?

CS Cancer Tarzana : Nikki Kem-Bernard
CS Cancer at Beverly Hills : Nikki Kem-Bernard
CS Cancer at Cedars-Sinai Medical Center : Nikki Kem-Bernard
Hunt Cancer Institute, an Affiliate of Cedars-Sinai Cancer

More about this Clinical Trial

What is the full name of this clinical trial?

NRG-BR008: A Phase III Randomized Trial of Radiotherapy Optimization for Low-Risk HER2- Positive Breast Cancer

Study Details

Disease Type/Condition

Breast

Principal Investigator

Giuliano, Armando

Co-Investigators

Alice Chung, Amin Mirhadi, Andrew Horodner, Benjamin King, Catherine Dang, David Chan, Dorothy Park, Farin Amersi, Hugo Hool, Jeannie Shen, Jin Sun Bitar, Johnny Chang, Julie Jang, Kjirsten Carlson, Lauren DeStefano, Marc Botnick, Marissa Boyle, Maryliza El-Masry, Michele Burnison, Monica Mita, Natasha Banerjee, Philomena McAndrew, Robert Reznik, Ryan Ponec, Scott Karlan, Stephen Shiao, Swati Sikaria, Syed Jilani, Thomas Lowe, Vanessa Dickey, Yuan Yuan

Age Group

Adult

Phase

III

IRB Number

STUDY00003133

ClinicalTrials.gov ID

NCT05705401

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Nikki Kem-Bernard

Nikki.Bernard@cshs.org