Clinical trial NCT04650490: SRS Timing With Immune Checkpoint Inhibition in Patients With Untreated Brain Metastases From Non-small Cell Lung Cancer
Official title: A Randomized, Phase II Trial of SRS Timing With Immune Checkpoint Inhibition in Patients With Untreated Brain Metastases From Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Brain Metastases
Non Small Cell Lung Cancer
Keywords: immunotherapy
Stereotactic radiosurgery
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2020-12-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Primary tumor histology must be one confirmed as one of the following:

   1. Squamous NSCLC
   2. Adenocarcinoma NSCLC
   3. Not otherwise specified NSCLC
3. Patient must have an MRI of the brain within 4 weeks (28 days) of signing the study consent.
4. Patient must be planned for immunotherapy treatment as their next systemic therapy, including monotherapy or in combination with chemotherapy.
5. Patients previously treated with a tyrosine kinase inhibitor (TKI) may be eligible, if a second line (or later) immunotherapy regimen is planned.
6. Patients must be asymptomatic or minimally symptomatic, requiring the equivalent of ≤2 mg dexamethasone/day for at least 7 days prior to enrollment.
7. Female and male subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in the Duke Contraception Policy.
8. Age ≥18 years of age at the time of entry into the study.
9. Karnofsky Performance Score (KPS) ≥70.

Exclusion Criteria:

1. Patients on the equivalent of \>2 mg of dexamethasone (or prednisone/steroid equivalent) daily ≤ 7 days before receiving study treatment.
2. Patients who have previously received whole brain radiation therapy (WBRT).
3. 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.
4. Patients with leptomeningeal carcinomatosis. However, patients with discrete dural-based lesions may be eligible at the discretion of the treating radiation oncologist.
5. Females who are pregnant or breastfeeding.
6. 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.
7. Patients with severe, active co-morbidity, defined as follows:

   1. Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax \> 99.5°F/37.5°C)
   2. Patients with known immunosuppressive disease or known uncontrolled human immunodeficiency virus infection
   3. Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
8. 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.
9. 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
10. Patients with a known history of hypersensitivity to the physician's choice of immune checkpoint inhibitor, or any components of the inhibitor.
11. Patients who have any contraindications to immunotherapy.
12. Patients with active autoimmune disease requiring systemic immunomodulatory treatment, including steroid of \>10 mg prednisone daily or equivalent, within the past 3 months.

Primary outcomes:
measure: Intracranial progression free-survival
timeFrame: from randomization through study completion, an average of 3 years
Secondary outcomes:
measure: Assess quality of life in each arm by the Functional Assessment of Cancer Therapy - Brain questionnaire
timeFrame: 1 year
measure: Assess neurocognitive outcome in each arm by the Hopkins Verbal Learning Test - Revised
timeFrame: 1 year
measure: Assess neurocognitive outcome in each arm by the Trail Making Test Parts A and B
timeFrame: 1 year
measure: Assess neurocognitive outcome in each arm by the Controlled Oral Word Association test
timeFrame: 1 year
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
Study officials:
affiliation: Duke Health
name: Scott Floyd, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke Health
name: Jeffrey Clarke, MD
role: PRINCIPAL_INVESTIGATOR
References: