Stereotactic Body Radiotherapy in Treating Patients with Oligometastatic Breast Cancer or Metastatic Non-small Cell Lung Cancer

This phase II trial studies how well stereotactic body radiotherapy (SBRT) works in treating patients with triple negative breast cancer that has spread to limited number of other places in the body (oligometastatic) or non-small cell lung cancer that has spread to other places in the body (metastatic). Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue.

Inclusion Criteria

• Metastatic disease detected on imaging and histologically confirmed: * Triple negative breast cancer (TNBC) (estrogen receptor [ER] < 1%, progesterone receptor [PR] < 1%, her-2-neu 0- 1+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH]-negative or as determined by Doctor of Medicine [MD] discretion) * ER positive (+) breast cancer receiving chemotherapy, regardless of HER2 status * Non-small cell lung cancer (NSCLC) without known targetable molecular alterations in EGFR, ALK or ROS1 * NSCLC with EGFR, ALK, or ROS1 targetable molecular alterations who had a history of disease progression on first-line tyrosine kinase inhibitor
• Patient can either have newly diagnosed metastatic disease, or have non-progressive disease on systemic therapy (for at least 3 months on systemic imaging)
• Patients must have measurable disease at baseline (Response Evaluation Criteria in Solid Tumors [RECIST] or Positron Emission Tomography Response Criteria in Solid Tumors [PERCIST] 2.0) and with 5 or fewer discrete disease sites that are technically amendable to SBRT (with the exception that if the primary disease is not amendable to SBRT it is allowed to be treated with conventionally fractionated or hypofractionated radiotherapy) * Two lesions in such close proximity to one another that treatment with one isocenter is more accurate and safer in the liver, lungs, or other similar anatomic locations should be viewed as one site of metastatic disease treatment * Disease in 2 contiguous vertebral bodies (with up to 6 cm of paraspinal extension) can represent one site of disease in the spine; non-contiguous lesions in vertebral bodies separated by one vertebral body free of disease should be viewed as 2 sites of treatment * If the clinical scenario deem that other forms of local therapy may be more suitable for the metastatic disease, such as surgical resection and interventional radiology-guided ablation, patients would be able to undergo other forms of local therapy with discussion with the principal investigator (PI)
• For de novo stage IV patients (patients with metastatic disease at first presentation), primary disease must be treatable with local therapy. If the primary tumor or other locoregional disease has not been definitively treated and is not amenable to SBRT, it must be treated with conventionally fractionated or hypofractionated radiotherapy using a regimen that delivers a minimum biological effective doses (BED) of 48 Gy. If the clinical scenario deem that other forms of local therapy may be more suitable for the primary and locoregional disease, such as surgical resection and interventional radiology-guided ablation, patients would be able to undergo other forms of local therapy with discussion with the PI
• If primary disease was previously treated with local therapy in the form of surgery or radiation, any new local/regional disease recurrence should be technically treatable with SBRT or hypofractionated radiation. If the clinical scenario deem that other forms of local therapy may be more suitable for the local/regional recurrent disease, such as surgical resection and interventional radiology-guided ablation, patients would be able to undergo other forms of local therapy with discussion with the PI
• Patients may receive palliative radiotherapy for symptomatic metastases or primary disease prior to enrollment provided that there is at least one other non-irradiated lesion amenable to SBRT at the time of enrollment
• Patients with brain metastases are eligible if these lesions have been treated prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status 0 – 2
• Able to provide informed consent
• Female subjects must either be of non-reproductive potential (i.e. post-menopausal by history: >= 60 years old or no menses for 1 > year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test within 2 weeks prior to starting treatment
• Adequate baseline organ function to allow SBRT to all relevant targets, as determined by the treating radiation oncologist based on lesion location, lesion size, and proximity to relevant organs at risk

Exclusion Criteria

• Serious medical co-morbidities precluding radiotherapy, determined at the discretion of the treating investigator
• Pregnant or lactating women
• Other active malignancy within the last year, even if without evidence of disease
• Clinical or radiological evidence of spinal cord compression
• Malignant pleural effusion or ascites
• Patients whose entry to the trial will cause unacceptable clinical delays in their planned management

PRIMARY OBJECTIVE:

I. To determine whether stereotactic body radiotherapy to all sites of metastatic disease in patients with oligometastatic non-small cell lung cancer or breast cancer improves progression free survival (PFS), defined as time from randomization to system disease progression (i.e. not intracranial progression) or death, as compared to standard of care therapy alone.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) and new metastasis incidence rate between standard of care and SBRT arms.

II. To assess local progression incidence rate at sites of SBRT and to characterize adverse events related to SBRT.

III. To compare quality of life of between standard of care and SBRT arms, using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core (C)30.

IV. To separately assess the PFS for breast cancer and non-small cell lung cancer (NSCLC) patients with or without SBRT.

CORRELATIVE OBJECTIVE:

I. Blood samples will be analyzed to characterize the tumor genetics, to discover meaningful biomarkers that allow for more effective and efficient use of SBRT for metastatic disease.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive standard of care in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo SBRT and then receive standard of care in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 1 year and then every 6 months for up to 2 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
T. Jonathan Yang

• Primary ID 18-486
• Secondary IDs NCI-2019-00436
• Clinicaltrials.gov ID NCT03808337