PROTOCOL: SWOG-S1703

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department at (810)762-8181, (810)762-8079 or (810)762-8038 to discuss full eligibility requirements.

ELIGIBILITY:

SCHEMA  S1703

Step 1 Registration:

1. Patients must have a diagnosis of hormone receptor positive (ER+ and/or PR+), HER-2 negative, metastatic (M1) breast cancer and must be receiving or plan to receive first line systemic treatment for metastatic disease. (Systemic treatment is any treatment meant to treat the whole body such as endocrine therapy +/- targeted therapy +/- chemotherapy).  Note: Participants are eligible if they have either de-nevo metastatic breast cancer and/or recurrent breast cancer from an earlier stage that is now metastatic.
2. Patients must be registered to Step 1 between 14 days prior to and 60 days after start of first line systemic treatment for metastatic disease.
3. Men or women at least 18 years of age.
4. Patients must have been tested for the following breast cancer specific STMs after diagnosis of metastatic disease and within 14 days initiation of first-line systemic treatment for metastatic disease: 1. CEA (must be tested. 2. CA 15-3 or CA27.29 (at least one of these must be tested).
5. Patients must have systemic radiographic imaging at any time prior to initiation of systemic therapy or within 30 days after initiation of systemic therapy. Imaging must be done prior to Step 1 registration. Modality of imaging is at the discretion of the treating physician.  Note: As this is a pragmatic trial, there is no limit on how long imaging may be done prior to Step 1 registration. Note: The treating physician may order additional imaging tests at any point prior to randomization at their discretion.
6. Patients must not be currently enrolled or plan to participate in a first-line treatment trial for metastatic breast cancer with a defined monitoring schedule.
7. Except for breast cancer (and previous history of breast cancer), no other prior malignancy is allowed with the following exceptions: 1. Adequately treated basal (or squamous cell) skin cancer. 2. Any cancer from which the patient has been disease free for five years. 3. Prior Stage 0 or pre-cancerous lesions that have been removed with clear margins.

Step 2 Registration:

1. Patients must be tested for the breast cancer specific STMs that were tested prior to Step 1 registration between 56 and 140 days after initiation of first-line systemic therapy for metastatic disease. 1. CEA (must be tested). 2. CA15-3 or CA 27.29 (whichever was tested prior to Step 1)  Testing all three STMs is encouraged but only two are required. Patients must plan to have the same two STMs tested for the duration that the patient is on protocol specified disease monitoring. At least one of the STMs that was previously elevated must have decreased from the assessment at Step 1 by greater than or equal to 10% at the time of Step 2 registration.

PROTOCOL: NRG-BR004

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department at (810)762-8181, (810)762-8079 or (810)762-8038  to discuss full eligibility requirements.

ELIGIBILITY:

SCHEMA  NRG-BR004

1. The study is open to male and female but must be at least 18 years of age.
2. ECOG Performance Status 0-1.
3. Histologically confirmed adenocarcinoma of the breast with locally recurrent, unresectable disease or metastatic disease outside the CNS.  Eligible patients include those with either: 1. De novo metastatic disease presenting without prior history of HER-2 positive breast cancer. Diagnosis should have been made from a biopsy of a metastatic disease site, but biopsy from the breast primary or involved regional lymph nodes is acceptable if biopsy of the metastatic sites was thought to carry excessive risk for the patient.  2. Locally recurrent or metastatic disease following prior therapy for early breast cancer. Diagnosis must have been made from the biopsy of the locally recurrent or metastatic disease. There must be an interval of equal to or greater than 6 months between completion of neo-adjuvant/adjuvant HER-2 targeted therapy and documentation of locally recurrent or metastatic HER-2 positive disease by biopsy.
4. Patients must have measurable disease as determine by the site, which has not been irradiated to be eligible.
5. Patients with brain metastases are eligible if they meet ALL the following criteria:

• Four or fewer metastatic sites to CNS
• Largest unexcised tumor does not exceed 3 cm
• No metastases to brain stem, midbrain, pons, medulla or the optic nerves and chiasm
• Must have measurable disease outside the CNS, based on RECIST 1.1, as determined by the
site, which has not been irradiated.
• If patient presented with symptoms from CNS metastases, the symptoms must have resolved
with initiation of steroids and initial local therapy (surgery, radiation therapy, or both).
• Must have been evaluated by Medical Oncologist and plan is to administer trastuzumab,
pertuzumab, and a taxane as first-line systemic therapy.
• May have received administration of trastuzumab OR lapatinib concurrently with radiation
therapy for brain metastases. Toxicities related to lapatinib if administered, should be
≤ grade 1 per the CTCAE v5.0, and the lapatinib must have been completed at least 2 weeks
prior to study entry.
• No history of intracranial hemorrhage or spinal cord hemorrhage.
• No neurosurgical resection or brain biopsy within 10 days prior to study entry.

6. Localized palliative radiation therapy to sites of non-measurable disease is allowed for symptom management and may begin prior to study entry and continue following study entry while receiving study therapy.

7. Patients must have imaging of the chest/abdomen/pelvis, preferably with a CT scan, and a bone scan within 5 weeks prior to study entry.

8. MRI of the brain must be obtained in patients with symptoms suggesting possible central nervous system metastatic disease. Neuroimaging is recommended but not required in asymptomatic patients.

INELIGIBILITY:

1. Patients with brain metastases are excluded if they meet ANY of the following criteria:

• Symptoms from brain metastases have not resolved prior to study entry
• Five or more clearly identified foci of metastases to the brain
• Largest unexcised tumor exceeds 3 cm
• Spinal cord metastases
• Medical Oncologist plans to employ HER2-directed tyrosine kinase inhibitor as component
of systemic therapy
• Metastatic disease limited to CNS

2. History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to study entry.