A Phase II Clinical Trial of Durvalumab (MEDI4736) and Fractionated Stereotactic Radiotherapy (fSRT) vs. Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR) for the Treatment of Brain Metastases From Non-Small Cell Lung Cancer (NSCLC)
Overview
- Phase
- Phase 2
- Intervention
- Stereotactic Radiation Therapy
- Conditions
- Brain Metastases from Non-small Cell Lung Cancer
- Sponsor
- University of Texas Southwestern Medical Center
- Enrollment
- 46
- Primary Endpoint
- Intercranial clinical benefit
- Status
- Withdrawn
- Last Updated
- last year
Overview
Brief Summary
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).
Investigators
Kiran Kumar
Assistant Professor
University of Texas Southwestern Medical Center
Eligibility Criteria
Inclusion Criteria
- •Biopsy-proven NSCLC primary with PD-L1 expression ≥ 1%
- •At least one previously untreated, asymptomatic brain metastases (\<=10 total) with at least one measurable (0.5 cm diameter or larger) as assessed by MRI
- •No prior systemic treatment for metastatic NSCLC.
- •age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Life expectancy greater than six (6) months
- •Adequate normal organ and marrow function
- •Body weight greater than 30 kg
- •Ability to understand and willingness to sign written informed consent
Exclusion Criteria
- •Brain metastases that are symptomatic and/or with recent (\<10 days) steroid use
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]).
- •Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
- •Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
- •Administration of one or more lines of systemic therapy for the diagnosis of metastatic non-small cell lung cancer
- •Prior receipt of systemic therapy for the management of high-risk early stage or locally advanced non-small cell lung cancer, prior to the development of metastatic disease, would not count towards the number of receipt of systemic therapy
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab or other agents used in study
- •Male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy
- •Participation in another clinical study with an investigational product during the last 1 month
Arms & Interventions
Durvalumab and standard fSRT
Fractionated stereotactic radiotherapy (fSRT) will be delivered to all previously untreated brain metastases noted at the time of treatment (up to 10 max). All brain metastases will be treated concurrently, 3 fractions total, delivered every other day (\~2 times/week) with first cycle of Durvalumab.
Intervention: Stereotactic Radiation Therapy
Durvalumab and standard fSRT
Fractionated stereotactic radiotherapy (fSRT) will be delivered to all previously untreated brain metastases noted at the time of treatment (up to 10 max). All brain metastases will be treated concurrently, 3 fractions total, delivered every other day (\~2 times/week) with first cycle of Durvalumab.
Intervention: Durvalumab
Durvalumab and PULSAR
Personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR), will be delivered to all previously untreated brain metastases noted at the time of treatment (up to 10 max). All brain metastases will be treated concurrently, 3 "pulses" of radiation total, delivered one pulse monthly with each cycle of Durvalumab.
Intervention: Stereotactic Radiation Therapy
Durvalumab and PULSAR
Personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR), will be delivered to all previously untreated brain metastases noted at the time of treatment (up to 10 max). All brain metastases will be treated concurrently, 3 "pulses" of radiation total, delivered one pulse monthly with each cycle of Durvalumab.
Intervention: Durvalumab
Outcomes
Primary Outcomes
Intercranial clinical benefit
Time Frame: 6 months after initiation of treatment
Intracranial clinical benefit (Complete Response, Partial Response, or Stable Disease) assessed per the brain modified (bm) RECIST (response evaluation criteria in solid tumors) criteria
Secondary Outcomes
- Quality of life questionnaire(6- and 12-months after initiation of treatment)
- Acute toxicity(6- and 12-months after initiation of treatment)