Clinical Trials /

SRS Timing With Immune Checkpoint Inhibition in Patients With Untreated Brain Metastases From Non-small Cell Lung Cancer

NCT04650490

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: Pro00106340
  • NCT ID: NCT04650490

Conditions

  • Brain Metastases
  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
ImmunotherapyImmediate IO followed by SRS

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Immediate SRS followed by IOExperimentalParticipants will receive SRS followed by physician's choice of standard of care immunotherapy, given at the FDA-approved dose within 14 days of SRS.
  • Immunotherapy
Immediate IO followed by SRSExperimentalParticipants 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.
  • Immunotherapy

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have 1 to 15 newly diagnosed brain metastases, ≤3 cm in the largest
             dimension, with at least one metastasis measuring ≥0.5 cm.

          -  Primary tumor histology must be one confirmed as one of the following:

               -  Squamous NSCLC

               -  Adenocarcinoma NSCLC

               -  Not otherwise specified NSCLC

          -  Patient must be able and willing to undergo a thin cut MRI at Duke, which is required
             for study entry.

          -  Patient must be planned for immunotherapy treatment as their next systemic therapy,
             including monotherapy or in combination with chemotherapy.

          -  Patients previously treated with a tyrosine kinase inhibitor (TKI) may be eligible, if
             a second line (or later) immunotherapy regimen is planned.

          -  Patients must be asymptomatic or minimally symptomatic, requiring the equivalent of ≤2
             mg dexamethasone/day for at least 7 days prior to enrollment.

          -  Female and male subjects of childbearing potential must be willing to use an adequate
             method of contraception as outlined in the Duke Contraception Policy.

          -  Age ≥18 years of age at the time of entry into the study.

          -  Karnofsky Performance Score (KPS) ≥70.

          -  Prothrombin and Partial Thromboplastin Times ≤1.2 x normal

          -  Neutrophil count ≥1000

          -  Hemoglobin ≥9 g/dl

          -  Platelet count ≥100,000/µl

          -  Creatinine ≤1.2 x normal range.

        Exclusion Criteria:

          -  Patients on the equivalent of >2 mg of dexamethasone daily ≤ 7 days before receiving
             study treatment

          -  Patients who have previously receive whole brain radiation therapy (WBRT).

          -  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 assuming an
             interval >6 months has passed from the completion of that therapy.

          -  Patients with leptomeningeal disease. However, patients with discrete dural-based
             lesions may be eligible.

          -  Females who are pregnant or breast-feeding.

          -  Patients with an impending, life-threatening cerebral hemorrhage or herniation, based
             on the assessment from a brain MRI of the study neurosurgeons or their designate.

          -  Patients with severe, active co-morbidity, defined as follows:

               -  Patients with an active infection requiring intravenous treatment or having an
                  unexplained febrile illness (Tmax > 99.5°F/37.5°C)

               -  Patients with known immunosuppressive disease or known uncontrolled human
                  immunodeficiency virus infection

               -  Patients with unstable or severe intercurrent medical conditions such as severe
                  heart disease (New York Heart Association Class 3 or 4)

          -  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:

          -  Patients with prior, unrelated malignancy requiring current active treatment in the
             last 3 years with the exception of cervical carcinoma in situ and adequately treated
             basal cell or squamous cell carcinoma of the skin

          -  Patients with a known history of hypersensitivity to the physician's choice of immune
             checkpoint inhibitor, or any components of the inhibitor.

          -  Patients who have any contraindications to immunotherapy.

          -  Patients with active autoimmune disease requiring systemic immunomodulatory treatment
             within the past 3 months.

          -  History and/or confirmed pneumonitis, or extensive bilateral lung disease on high
             resolution/spiral CT scan.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Intracranial progression free-survival
Time Frame:from randomization through study completion, an average of 3 years
Safety Issue:
Description: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

Measure:Assess quality of life in each arm by the FACT-BR questionnaire
Time Frame:1 year
Safety Issue:
Description:as measured from 0 (not at all) through 4 (very much)
Measure:Assess neurocognitive outcome in each arm by the Hopkins Verbal Learning Test - Revised
Time Frame:1 year
Safety Issue:
Description:as measured by recall scores with higher values indicating better outcomes
Measure:Assess neurocognitive outcome in each arm by the Trail Making Test Parts A and B
Time Frame:1 year
Safety Issue:
Description:scored as average or deficient based on time to complete the activity
Measure:Assess neurocognitive outcome in each arm by the Controlled Oral Word Association test
Time Frame:1 year
Safety Issue:
Description:scored as the number of words completed in one minute, with higher score indicating better outcome

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Duke University

Trial Keywords

  • immunotherapy
  • Stereotactic radiosurgery

Last Updated

December 2, 2020