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

Trial Summary

What is the purpose of this trial?

This trial is studying how the timing of precise brain radiation and immune-boosting therapy affects patients with lung cancer that has spread to the brain.

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.

What data supports the effectiveness of the treatment involving Immune Checkpoint Inhibition and Stereotactic Radiosurgery?

Research shows that immune checkpoint inhibitors can be effective in treating solid tumors, even in patients with poor health status, with some patients experiencing improved survival rates. Additionally, patients who developed immune-related side effects while on these inhibitors had better survival outcomes, suggesting a potential link between the treatment and improved prognosis. ^{1 2 3 4 5}

What is the safety profile of immune checkpoint inhibitors?

Immune checkpoint inhibitors can cause unique side effects called immune-related adverse events (irAEs), which may affect the skin, gut, hormones, and liver, and less commonly, other organs like the eyes and lungs. These side effects can be serious and sometimes life-threatening, requiring careful management and sometimes hospitalization. ^{6 7 8 9 10}

How does immune checkpoint inhibition differ from other cancer treatments?

Immune checkpoint inhibition is unique because it works by blocking proteins that prevent the immune system from attacking cancer cells, effectively 'releasing the brakes' on the immune system. This approach can lead to a more durable response compared to traditional treatments, as it helps the body's own immune cells recognize and destroy cancer cells. ^{11 12 13 14 15}

Research Team

Jeffrey Clarke, MD

Principal Investigator

Duke Health

Scott Floyd, MD PhD

Principal Investigator

Duke Health

Eligibility Criteria

Inclusion Criteria

Squamous NSCLC

Adenocarcinoma NSCLC

Not otherwise specified NSCLC

Timeline

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

Treatment Details

Interventions

• Immune Checkpoint Inhibition
• Stereotactic Radiosurgery

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. India pubmed.ncbi.nlm.nih.gov

Association of Immune-Related Adverse Effects and Survival in Solid Tumor Patients Treated with PD1 Inhibitors. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Inpatient utilization of immune checkpoint inhibitors and clinical outcomes. [2023]

4. United States 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. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Prognostic Nutritional Index Predicts Response and Prognosis in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. [2021]

7. England pubmed.ncbi.nlm.nih.gov

A multidisciplinary approach to toxicity management of modern immune checkpoint inhibitors in cancer therapy. [2018]

8. Canada 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. [2020]

9. United States 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. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Tumors attenuating the mitochondrial activity in T cells escape from PD-1 blockade therapy. [2021]

12. England pubmed.ncbi.nlm.nih.gov

The blockade of immune checkpoints in cancer immunotherapy. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab-induced Autoimmune Diabetes in a Patient with Metastatic Breast Cancer: A Case Report. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer. [2022]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Current Progress and Future Perspectives of Immune Checkpoint in Cancer and Infectious Diseases. [2021]