Radiosurgery + Immunotherapy for Brain Metastases from Lung Cancer

(STICk-IM-NSCLC Trial)

Overseen By Joan Cahill, BNS OCN CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must be taking: Immunotherapy

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Pregnancy, Severe heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days for initial treatment phase

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the timing of two treatments—stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (a type of immunotherapy)—affects patients with non-small cell lung cancer that has spread to the brain. Researchers aim to determine if altering the order of these treatments impacts their effectiveness. Individuals with 1 to 15 newly diagnosed brain spots from this lung cancer may be suitable candidates, particularly if they plan to start immunotherapy soon. Participants should have minimal symptoms and manage well on a small dose of steroids, such as dexamethasone. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on more than 2 mg of dexamethasone or similar steroids daily, you may need to adjust your dosage before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that immune checkpoint inhibitors, a type of cancer treatment, can cause some side effects. For instance, liver problems have been reported in 2% to 10% of patients using drugs like ipilimumab, nivolumab, and pembrolizumab. Although serious lung issues have also been noted, they are rare.

In contrast, stereotactic radiosurgery (SRS) is generally considered safe and effective. It precisely targets brain tumors, affecting only the tumor and not the surrounding healthy tissue. This approach reduces side effects for most patients.

These treatments have shown promise when used together, but awareness of potential risks is important. Always consult healthcare professionals to understand what this means for your specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of SRS (stereotactic radiosurgery) and immune checkpoint inhibitors for treating brain metastases from non-small cell lung cancer because it's an innovative approach that optimizes the timing and sequence of treatments. Unlike traditional treatments, which may involve separate radiotherapy and immunotherapy schedules, this approach tests whether immediate SRS followed by immunotherapy or vice versa can improve patient outcomes. This trial is particularly promising because it aims to harness the immune system's power to attack cancer cells more effectively when combined with precise radiation therapy, potentially leading to better control of brain metastases and improved survival rates.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer with brain metastases?

Research has shown that combining immune checkpoint inhibitors with stereotactic radiosurgery (SRS) can improve outcomes for patients with brain metastases from non-small cell lung cancer (NSCLC). In this trial, participants will be assigned to different treatment arms to evaluate these combinations. One study found a 13% higher one-year survival rate when these treatments were combined, compared to their separate use. Another analysis indicated a 38% reduction in the risk of death for patients receiving both treatments compared to those receiving only SRS. These findings suggest that using these treatments together might more effectively control the disease in the brain and improve overall survival chances. ^{6 7 8 9 10}

Who Is on the Research Team?

Jeffrey Clarke, MD

Principal Investigator

Duke Health

Scott Floyd, MD PhD

Principal Investigator

Duke Health

Are You a Good Fit for This Trial?

Inclusion Criteria

Squamous NSCLC

Adenocarcinoma NSCLC

Not otherwise specified NSCLC

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either immediate SRS followed by immunotherapy or immediate immunotherapy followed by SRS

14 days for initial treatment phase

Follow-up

Participants are monitored for intracranial progression and quality of life

3 years

Long-term follow-up

Participants' neurocognitive outcomes are assessed over time

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Immune Checkpoint Inhibition
• Stereotactic Radiosurgery

How Is the Trial Designed?

Group I: Immediate SRS followed by IO Experimental Treatment 2 Interventions

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.

Group II: Immediate IO followed by SRS Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

In a study of 155 patients with advanced solid tumors, those with a better performance status (ECOG PS 0-1) had a median overall survival (OS) of 9.1 months, compared to only 2.9 months for those with poorer performance status (ECOG PS 2-4), indicating that performance status significantly impacts treatment outcomes with immune checkpoint inhibitors (ICIs).

Despite having a poor performance status, 27.3% of patients in the study were still alive after one year, and the treatment was generally well-tolerated, with 84.6% of patients experiencing no severe toxicities, suggesting that ICIs can be a safe and effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings. Kapoor, A., Noronha, V., Patil, VM., et al.[2023]

Chemotherapy following immune checkpoint inhibitors (ICI) shows high effectiveness in patients with recurrent or metastatic head and neck squamous cell carcinoma, with a median overall survival of 20 months and a 12-month overall survival rate of 63.3%.

Inflammatory and nutritional factors, such as the Neutrophil-to-Lymphocyte Ratio (NLR) and the Prognostic Nutrition Index (PNI), are significantly correlated with patient prognosis, indicating that these factors may help predict outcomes after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy following immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma: clinical effectiveness and influence of inflammatory and nutritional factors. Sakai, A., Ebisumoto, K., Iijima, H., et al.[2023]

The study developed a framework using real-world data from the FDA's Adverse Event Reporting System to detect and filter immune-related adverse events (irAEs) associated with six FDA-approved immune checkpoint inhibitors, identifying 94 positive signals.

Out of these signals, 31 (33%) were classified as potentially new irAEs, highlighting the framework's effectiveness in discovering novel safety concerns that may not be documented in existing drug labels or literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detecting and Filtering Immune-Related Adverse Events Signal Based on Text Mining and Observational Health Data Sciences and Informatics Common Data Model: Framework Development Study. Yu, Y., Ruddy, K., Mansfield, A., et al.[2020]

A systematic review identified 265 types of rare adverse events associated with immune checkpoint inhibitors, with the most common being autoimmune type I diabetes, pneumonitis, myocarditis, and colitis, highlighting the diverse side effects of these cancer treatments.

This review emphasizes the importance of using peer-reviewed literature to compile adverse event data, providing a reliable resource for clinicians to better understand and manage the potential risks of checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rare Adverse Events with Programmed Death-1 and Programmed Death-1 Ligand Inhibitors: Justification and Rationale for a Systematic Review. Smith, CJ., Almodallal, Y., Jatoi, A.[2023]

In a study analyzing 2,088 individual case safety reports (ICSRs) related to immune checkpoint inhibitors (ICIs) in Italy, 801 reports documented serious immune-related adverse drug reactions (irADRs), primarily affecting male patients with gastrointestinal and skin toxicities.

Among the ICIs, nivolumab and pembrolizumab were most frequently associated with irADRs, with significant risks identified for pembrolizumab and ipilimumab, highlighting the need for oncologists to recognize and manage these serious side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. Ruggiero, R., Fraenza, F., Scavone, C., et al.[2022]

In a study of 52 hospitalized cancer patients treated with immune checkpoint inhibitors, 68.2% either died or were admitted to hospice within 90 days, indicating a high rate of poor outcomes in this population.

Patients who had not previously received immune checkpoint inhibitors before hospitalization had a significantly shorter time to death or hospice (29 days) compared to those who had prior treatment (242 days), suggesting that prior exposure to these therapies may influence survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inpatient utilization of immune checkpoint inhibitors and clinical outcomes. Wang, J., Lee, CS., Attarian, S., et al.[2023]

Immune checkpoint inhibitors are promising immunomodulatory agents that help reactivate immune cells to fight tumors, showing significant effectiveness in treating solid cancers like melanoma and non-small cell lung cancer.

Numerous clinical studies are currently investigating the benefits of these inhibitors across various cancer types, with a particular focus on their application in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer. Gaynor, N., Crown, J., Collins, DM.[2022]

A review of 2217 adverse drug reaction reports related to immune checkpoint inhibitors (ICIs) from 2011 to 2018 revealed that these drugs, particularly nivolumab, are associated with a higher frequency of serious immune-related adverse events, including gastrointestinal and respiratory disorders.

Emerging safety signals, such as ischaemic heart disease and cardiac failure, were identified, indicating the need for further investigation into the long-term safety profile of ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. Cutroneo, PM., Isgrò, V., Ientile, V., et al.[2021]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK594965/

Combined Stereotactic Radiosurgery and Immune Checkpoint ... The one-year overall survival rate was 13% higher in the concurrent SRS and ICIs group than in the non-concurrent treatment group (51.6% versus 64.6%); Q < ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1015958422013331

Stereotactic radiosurgery combined with immune ... Our analyses indicate that the risk of death of patients receiving SRS + ICI is reduced by 38% compared to patients receiving SRS alone. A few studies suggested ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2806787

Checkpoint Inhibitors in Combination With Stereotactic ... This randomized clinical trial assesses the addition of radiotherapy to immune checkpoint inhibitors compared with immune checkpoint ...

4. thejns.org thejns.org/view/journals/j-neurosurg/138/6/article-p1591.pdf

Effectiveness of immune checkpoint inhibitors in Thus, we investigated differences in patient survival, intracranial disease control, and toxicity between SRS alone and SRS combined with ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT227255

A meta-analysis of patient-level data. At 1-year, OS for all studies was 58% (95% confidence interval [CI]: 51.9-63.8%) with improved survival for concurrent versus non-concurrent (p < .01) therapy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10247998/

Immune-related adverse events of immune checkpoint ... Hepatotoxicity has been reported in 2% to 10% of patients receiving monotherapy with ipilimumab, nivolumab, and pembrolizumab. Combination ...

7. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1665716/full

Safety of immune checkpoint inhibitors for cancer treatment The most common fatal irAEs was pneumonitis (n=5; 25%) with median time to death of 6 days. Cardiac, hepatic, and renal systems were equally affected (n=4; 20%) ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e24104

Real world data of safety of immune-checkpoint inhibitors ... This retrospective cohort study investigated the use of immune checkpoint inhibitor (ICI) therapy in an oncology and hematology patients treated at King Fahad ...

9. jitc.bmj.com jitc.bmj.com/content/12/3/e008724

Clinical outcomes and safety of immune checkpoint ... Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns.

10. nature.com nature.com/articles/s41571-022-00600-w

Immune-checkpoint inhibitors: long-term implications of ... In this Review, we describe the current evidence for chronic immune toxicities and the long-term implications of these effects for patients receiving ICIs.