20 Participants Needed

Immunotherapy with Steroids for Brain Metastases

(ACT-FAST Trial)

JW
Overseen ByJohn Walker
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: AHS Cancer Control Alberta
Must be taking: Corticosteroids
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 4 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

Immunotherapy treatments are intended to boost a person's immune system to fight their cancer. Treatment with immunotherapy has been shown to be effective in a wide range of cancers, including melanoma skin cancer, lung cancer and kidney cancer, among others. Steroids are anti-inflammatory medications which may suppress the immune system. For this reason, persons requiring treatment with steroids have not previously been allowed to participate in immunotherapy clinical trials. Therefore, we do not know whether or not immunotherapy treatments are effective in patients who are also receiving treatment with steroids. When cancer has spread to the brain swelling may occur around the tumors, and headache, nausea, seizures or stroke-like symptoms may occur. In this instance, steroids are important to reduce swelling within the brain, thus alleviating these symptoms. Because patients requiring treatment with steroids have not previously been allowed to participate in immunotherapy clinical trials, we do not know whether treatment with immunotherapy is effective when steroid treatments are also used. This study will investigate this question, and also attempt to determine whether treatment with one steroid versus another results in a better response to immunotherapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you are already on corticosteroid therapy. If you are taking non-steroid immunosuppressive agents, you will not be eligible for this study.

What data supports the effectiveness of the drug combination Nivolumab and Ipilimumab for treating brain metastases?

Research shows that the combination of Nivolumab and Ipilimumab can lead to significant responses in brain metastases, particularly in patients with melanoma, with over 50% of asymptomatic patients showing an intracranial response. Additionally, a case study reported an exceptional response in a patient with brain metastases from lung cancer using Nivolumab while on high-dose steroids.12345

Is the combination of Nivolumab and Ipilimumab safe for humans?

The combination of Nivolumab and Ipilimumab has been used in patients with advanced melanoma and non-small-cell lung cancer, but it can cause serious side effects. In a study, about half of the patients experienced severe side effects, and many needed hospital care. While it can help some patients live longer, the treatment comes with significant risks.14678

How is the drug combination of Nivolumab and Ipilimumab unique for treating brain metastases?

The combination of Nivolumab and Ipilimumab is unique because it can induce significant responses in brain metastases, even in patients who are symptomatic or on steroids, which is challenging for other treatments. This drug combination works by enhancing the immune system's ability to fight cancer cells in the brain, offering a novel approach compared to traditional therapies.12349

Eligibility Criteria

This trial is for adults with brain tumors who need steroids to reduce swelling and have started steroid therapy. They must be eligible for standard immunotherapy, have measurable brain disease, stable thyroid issues on hormones if present, and use birth control if applicable. Excluded are those with HIV, hepatitis B/C, recent autoimmune treatments or severe drug allergies.

Inclusion Criteria

I am able to get out of my bed or chair and move around.
My thyroid condition is stable with medication.
I have been diagnosed with melanoma, lung, kidney, or genitourinary cancer.
See 10 more

Exclusion Criteria

I have a history of HIV, Hepatitis B, or Hepatitis C.
I have been treated for an autoimmune disease in the last 2 years.
I am taking medication that suppresses my immune system, but it's not a steroid.
See 1 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immunotherapy while on corticosteroid therapy to assess efficacy and safety

24 weeks
Baseline imaging, followed by assessments every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months
Regular follow-up visits as part of standard care

Treatment Details

Interventions

  • Accelerated Checkpoint Therapy
  • Glucocorticoid therapy
Trial OverviewThe study tests whether immunotherapy can still work effectively in patients who also require steroids due to brain metastases from cancers like melanoma or lung cancer. It compares the effects of different steroids alongside standard immune checkpoint inhibitors.
Participant Groups
2Treatment groups
Active Control
Group I: PrednisoneActive Control1 Intervention
Dose starting at 25 mg/day (a calculation of equipotent steroid equivalencies will be used).
Group II: DexamethasoneActive Control1 Intervention
Dose starting at 4 mg daily (for patients randomized to the Dexamethasone arm).

Accelerated Checkpoint Therapy is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Opdivo + Yervoy for:
  • Melanoma
  • Renal cell carcinoma
  • Colorectal cancer
  • Hepatocellular carcinoma
  • Non-small cell lung cancer
🇺🇸
Approved in United States as Opdivo + Yervoy for:
  • Melanoma
  • Renal cell carcinoma
  • Colorectal cancer
  • Hepatocellular carcinoma
  • Non-small cell lung cancer
🇨🇦
Approved in Canada as Opdivo + Yervoy for:
  • Melanoma
  • Renal cell carcinoma
  • Colorectal cancer
🇯🇵
Approved in Japan as Opdivo + Yervoy for:
  • Melanoma
  • Renal cell carcinoma
  • Non-small cell lung cancer

Find a Clinic Near You

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials
188
Recruited
26,900+

Findings from Research

Nivolumab plus ipilimumab significantly improved overall survival in patients with metastatic non-small cell lung cancer (NSCLC), including those with baseline brain metastases, compared to chemotherapy, with a hazard ratio of 0.63 for those with brain metastases and 0.76 for those without.
At 5 years, patients with baseline brain metastases treated with nivolumab plus ipilimumab had higher rates of systemic (12%) and intracranial (16%) progression-free survival compared to chemotherapy (0% and 6%, respectively), and fewer developed new brain lesions (4% vs. 20%).
Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1.Reck, M., Ciuleanu, TE., Lee, JS., et al.[2023]
A patient with lung cancer brain metastases showed an exceptional and lasting response to short-term nivolumab immunotherapy, despite being on high-dose steroids and having low PDL1 expression, which are typically poor indicators for treatment success.
This case highlights the potential for immunotherapy to yield significant benefits even in challenging circumstances and emphasizes the need for ongoing follow-up after treatment, regardless of initial prognosis.
Exceptional response of brain metastases to short course nivolumab while on high-dose steroids.de Jong, WK., Mulders, ACM., Westendorp, W., et al.[2020]
Immunotherapy, particularly with anti-CTLA4 and anti-PD-1 antibodies, shows promising efficacy in treating brain metastases from melanoma, achieving durable responses in 15%-20% of asymptomatic patients and over 50% when combined, but effectiveness drops significantly in symptomatic patients or those on corticosteroids.
The study highlights the need for further research to enhance response rates and reduce toxicity in immunotherapy for brain metastases, suggesting that understanding resistance mechanisms and exploring novel agents could improve treatment outcomes.
Emergent immunotherapy approaches for brain metastases.Wang, J., Tawbi, HA.[2021]

References

Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1. [2023]
Exceptional response of brain metastases to short course nivolumab while on high-dose steroids. [2020]
Emergent immunotherapy approaches for brain metastases. [2021]
Intracranial antitumor responses of nivolumab and ipilimumab: a pharmacodynamic and pharmacokinetic perspective, a scoping systematic review. [2020]
Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. [2022]
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. [2022]
Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands. [2023]
Unmasking of intracranial metastatic melanoma during ipilimumab/nivolumab therapy: case report and literature review. [2018]
Ipilimumab plus nivolumab in patients with symptomatic melanoma brain metastasis requiring corticosteroids. [2023]