This is a research study to find out if the new anti-cancer drug Durvalumab combined with radiation therapy to the brain will work in treating brain metastases from non-small cell lung cancer (NSCLC). Focused, highly precise radiation therapy to the brain, known as stereotactic radiosurgery (SRS), is a standard of care treatment that is commonly used for patients with metastatic lung cancer to the brain. It is standardly used as an alternative to surgery to eradicate the targeted tumours in the brain and prevent them from growing and causing symptoms. This study will look at the combination of the novel immunotherapy Durvalumab with two different ways of delivering SRS: 1) with each radiation treatment given every other day for 3 treatments with the first dose of Durvalumab (fSRT), or 2) with each radiation treatment, referred to as a "pulse," given every 4 weeks with each dose of Durvalumab for 3 treatments (PULSAR).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
24-27 Gy in 3 fractions- one plan, given once every other day with first cycle of Durvalumab for comparator arm. 24-27 Gy in 3 "pulses"- each pulse of radiation re-planned, given once every 4 weeks with each Durvalumab for experimental arm.
Durvalumab (initially developed as MEDI4736) is a human monoclonal antibody of the immunoglobulin (Ig) G1 kappa subclass that inhibits binding of PD-L1 (B7-H1, CD274) to PD-1 (CD279) and CD80 (B7-1). MEDI4736 is composed of 2 identical heavy chains and 2 identical light chains, with an overall molecular weight of approximately 149 kDa. MEDI4736 contains a triple mutation in the constant domain of the Ig G1 heavy chain that reduces binding to complement protein C1q and the fragment crystallizable gamma receptors involved in triggering effector function.
Intercranial clinical benefit
Intracranial clinical benefit (Complete Response, Partial Response, or Stable Disease) assessed per the brain modified (bm) RECIST (response evaluation criteria in solid tumors) criteria
Time frame: 6 months after initiation of treatment
Acute toxicity
All acute toxicities (CNS and non-CNS) will be evaluated using the NCI Common Terminology Criteria of Adverse Events (CTCAE) version 5.0, with results tabulated to examine frequency, severity, organs affected, and relationship to study treatment.
Time frame: 6- and 12-months after initiation of treatment
Quality of life questionnaire
Functional Assessment of Cancer Therapy brain (FACT-Br) questionnaires. scoring range 0-200. Higher the score, the better the QOL
Time frame: 6- and 12-months after initiation of treatment
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