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

NCT04650490 | Withdrawn Phase 2

• 1 other identifier: Pro00106340
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Metastases; Non Small Cell Lung Cancer

Keywords

immunotherapy; Stereotactic radiosurgery

Outcome Measures

Primary Outcomes (1)

• Intracranial progression free-survival

  Defined as defined as time to intracranial progression from randomization measured by by RANO-BM criteria for radiographic progression on contrast-enhanced brain MRI

  from randomization through study completion, an average of 3 years

Secondary Outcomes (4)

• Assess quality of life in each arm by the Functional Assessment of Cancer Therapy - Brain questionnaire

  1 year

• Assess neurocognitive outcome in each arm by the Hopkins Verbal Learning Test - Revised

  1 year

• Assess neurocognitive outcome in each arm by the Trail Making Test Parts A and B

  1 year

• Assess neurocognitive outcome in each arm by the Controlled Oral Word Association test

  1 year

Study Arms (2)

Immediate SRS followed by IO

EXPERIMENTAL

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; Drug: Immunotherapy

Immediate IO followed by SRS

EXPERIMENTAL

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; Drug: Immunotherapy

Interventions

Stereotactic Radiosurgery RADIATION

Timing of stereotactic radiosurgery relative to immunotherapy

Immediate IO followed by SRS; Immediate SRS followed by IO

Immunotherapy DRUG

Physician's choice of immunotherapy per standard of care

Immediate IO followed by SRS; Immediate SRS followed by IO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Primary tumor histology must be one confirmed as one of the following:
• Squamous NSCLC
• Adenocarcinoma NSCLC
• Not otherwise specified NSCLC
• Patient must have an MRI of the brain within 4 weeks (28 days) of signing the study consent.
• 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.

You may not qualify if:

• Patients on the equivalent of \>2 mg of dexamethasone (or prednisone/steroid equivalent) daily ≤ 7 days before receiving study treatment.
• Patients who have previously received 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 after an interval of \>6 months has passed from the completion of that therapy.
• Patients with leptomeningeal carcinomatosis. However, patients with discrete dural-based lesions may be eligible at the discretion of the treating radiation oncologist.
• Females who are pregnant or breastfeeding.
• 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.
• 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, prostate cancer at stage I-III 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, including steroid of \>10 mg prednisone daily or equivalent, within the past 3 months.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Radiosurgery; Immunotherapy

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Immunomodulation; Biological Therapy

Study Officials

• Scott Floyd, MD PhD

  Duke Health

  PRINCIPAL INVESTIGATOR

• Jeffrey Clarke, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: December 2, 2020
• Study Start: March 1, 2023
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: March 2, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)