STICk-IM-NSCLC: SRS Timing With Immune Checkpoint Inhibition in Patients With Untreated Brain Metastases From Non-small Cell Lung Cancer
Study Details
Study Description
Brief Summary
This trial is a randomized, 2-arm, phase II study to determine the effect, if any, of the timing of stereotactic radiosurgery (SRS) relative to immune checkpoint inhibitor (IO) therapy in patients with non-small cell lung cancer (NSCLC) that has spread (metastasized) to the brain.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Immediate SRS followed by IO Participants will receive SRS followed by physician's choice of standard of care immunotherapy, given at the FDA-approved dose within 14 days of SRS. |
Radiation: Stereotactic Radiosurgery
Timing of stereotactic radiosurgery relative to immunotherapy
Drug: Immunotherapy
Physician's choice of immunotherapy per standard of care
|
| Experimental: Immediate IO followed by SRS Participants will receive physician's choice of immunotherapy, given at the FDA-approved dose followed by SRS, if deemed appropriate, at the time of intracranial progression. |
Radiation: Stereotactic Radiosurgery
Timing of stereotactic radiosurgery relative to immunotherapy
Drug: Immunotherapy
Physician's choice of immunotherapy per standard of care
|
Outcome Measures
Primary Outcome Measures
- Intracranial progression free-survival [from randomization through study completion, an average of 3 years]
Defined as defined as time to intracranial progression from randomization measured by by RANO-BM criteria for radiographic progression on contrast-enhanced brain MRI
Secondary Outcome Measures
- Assess quality of life in each arm by the Functional Assessment of Cancer Therapy - Brain questionnaire [1 year]
as measured on a 5 point Likert-type scale from 0 (not at all) through 4 (very much) where the higher score reflects better quality of life
- Assess neurocognitive outcome in each arm by the Hopkins Verbal Learning Test - Revised [1 year]
as measured by recall scores with higher values indicating better outcomes
- Assess neurocognitive outcome in each arm by the Trail Making Test Parts A and B [1 year]
scored as average or deficient based on time to complete the activity
- Assess neurocognitive outcome in each arm by the Controlled Oral Word Association test [1 year]
scored as the number of words completed in one minute, with higher score indicating better outcome
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have 1 to 15 newly diagnosed brain metastases, ≤5 cm in the largest dimension, with at least one metastasis measuring ≥0.3 cm.
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Primary tumor histology must be one confirmed as one of the following:
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Squamous NSCLC
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Adenocarcinoma NSCLC
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Not otherwise specified NSCLC
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Patient must have an MRI of the brain within 4 weeks (28 days) of signing the study consent.
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Patient must be planned for immunotherapy treatment as their next systemic therapy, including monotherapy or in combination with chemotherapy.
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Patients previously treated with a tyrosine kinase inhibitor (TKI) may be eligible, if a second line (or later) immunotherapy regimen is planned.
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Patients must be asymptomatic or minimally symptomatic, requiring the equivalent of ≤2 mg dexamethasone/day for at least 7 days prior to enrollment.
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Female and male subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in the Duke Contraception Policy.
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Age ≥18 years of age at the time of entry into the study.
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Karnofsky Performance Score (KPS) ≥70.
Exclusion Criteria:
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Patients on the equivalent of >2 mg of dexamethasone (or prednisone/steroid equivalent) daily ≤ 7 days before receiving study treatment.
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Patients who have previously received whole brain radiation therapy (WBRT).
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Patients must not have ever received immunotherapy in the stage IV setting. Prior immune therapy as part of treatment for stage I-III disease is allowed after an interval of >6 months has passed from the completion of that therapy.
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Patients with leptomeningeal carcinomatosis. However, patients with discrete dural-based lesions may be eligible at the discretion of the treating radiation oncologist.
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Females who are pregnant or breastfeeding.
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Patients with an impending, life-threatening cerebral hemorrhage or herniation, based on the assessment from a brain MRI of the study neurosurgeons or their designee.
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Patients with severe, active co-morbidity, defined as follows:
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Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C)
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Patients with known immunosuppressive disease or known uncontrolled human immunodeficiency virus infection
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Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
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Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used.
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Patients with prior, unrelated malignancy requiring current active treatment in the last 3 years with the exception of cervical carcinoma in situ, prostate cancer at stage I-III and adequately treated basal cell or squamous cell carcinoma of the skin
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Patients with a known history of hypersensitivity to the physician's choice of immune checkpoint inhibitor, or any components of the inhibitor.
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Patients who have any contraindications to immunotherapy.
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Patients with active autoimmune disease requiring systemic immunomodulatory treatment, including steroid of >10 mg prednisone daily or equivalent, within the past 3 months.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Duke Cancer Center | Durham | North Carolina | United States | 27710 |
Sponsors and Collaborators
- Duke University
Investigators
- Principal Investigator: Scott Floyd, MD PhD, Duke Health
- Principal Investigator: Jeffrey Clarke, MD, Duke Health
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Pro00106340