Clinical Trial Information
PROTOCOL: NRG-BR004
SCHEMA NRG BR004
Please. Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.
ELIGIBILITY:
- The trial is open to female and male patients, must be ≥ 18 years old.
- Patient must have an ECOG Performance Status of 0 or 1.
- Histologically confirmed adenocarcinoma of the breast with locally recurrent, unresectable disease or metastatic disease confirmed as described below. Eligible patients include those with either:
- De novo metastatic disease presenting without prior history of HER2-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.
- 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 ≥ 6 months between completion of neoadjuvant/adjuvant HER2-targeted therapy and documentation of locally recurrent or metastatic HER2- positive disease by biopsy.
- Patients must have measurable disease.
- The tumor specimen obtained at the time of diagnosis of locally recurrent or metastatic disease must have been determined to be HER2-positive.
- The tumor specimen obtained at the time of diagnosis used for HER2 testing must also have central testing for PD-L1 status. Patients will be eligible irrespective of PD-L1 testing result including PD-L1 indeterminant.
- The tumor specimen obtained at the time of diagnosis used for HER2 and PD-L1 testing should also have central testing for ER and PgR. Patients with < 1% ER and PgR staining by IHC will be classified as negative. If sufficient material for central confirmation of ER and PgR is unavailable, local testing results for ER and PgR may be used for eligibility.
- Localized palliative radiation therapy is allowed for symptom management if completed ≥ 14 days prior to randomization.
- Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
- Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
− Evaluable or measurable disease outside the CNS
− No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of
the optic apparatus (optic nerves and chiasm)
− No history of intracranial hemorrhage or spinal cord hemorrhage
− No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of
anticonvulsants are permitted.
− No neurosurgical resection or brain biopsy within 28 days prior to randomization.
- Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
− Radiographic demonstration of improvement upon the completion of CNS directed
therapy and no evidence of interim progression between the completion of CNS directed
therapy and the screening radiographic study
− No stereotactic radiation or whole-brain radiation within 4 weeks prior to randomization.
− Screening CNS radiographic study at least 4 weeks from completion of radiotherapy and
at least 2 weeks from discontinuation of corticosteroids.
- N0 history of systemic anti-cancer therapy (e.g., chemotherapy, targeted therapy) for MBC with the exception of administration of trastuzumab or lapatinib concurrently with radiation therapy for brain metastases. Toxicities related to lapatinib should be ≤ grade 1, and must have been completed at least 2 weeks prior to randomization.
- No history of exposure to cumulative doses of doxorubicin greater than 360 mg per square meter of body-surface area or its equivalent.
- No prior treatment with mTOR inhibitors or CDK 4/6 inhibitors in combination with endocrine therapy for treatment of metastatic disease.
- No prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including antiCD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
- No 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 randomization.
