Brodalumab in the Treatment of Immune-Related Adverse Events
Safety and Efficacy of Brodalumab in the Treatment of Immune-Related Adverse Events: A Pilot Study
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Time periods mentioned: 24 weeks
- Procedures mentioned: Questionnaires
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "Subjects will receive subcutaneous brodalumab for 24 weeks."
- "All patients will have the Columbia Suicide Severity Rating Scale (C-SSRS), and Patient Health Questionnaire-9 (PHQ-9) administered at all visits."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests how safe brodalumab is and how well it controls side effects from cancer immune therapy. It is for adults with advanced cancer whose side effects may involve an immune system protein called IL-17. Brodalumab is not FDA-approved for treating these side effects.
The purpose of this study is to test the safety and effectiveness of using brodalumab in patients who develop side effects from cancer immune therapy. Immune-related side effects are due to activation of the immune system in patients who previously received immunotherapy and the goal of this study is to help better control these side effects. Brodalumab is often used to treat patients with autoimmune diseases (diseases where the immune system is activated against normal organs) and safe doses and treatment schedules have been determined in these patients. Immune-related side effects appear to closely mirror these autoimmune conditions. Brodalumab has not been approved by the United States Food and Drug Administration (FDA) for use in immunotherapy side effects but it has been approved for treatment of autoimmune conditions.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- You must be older than 18. You or your guardian must give written consent.
- You must have side effects from cancer immune therapy that doctors think are linked to IL-17.
- You must have taken, or plan to take, steroids that work throughout the body to treat these side effects.
- A tissue test must confirm a solid-organ cancer that is advanced or has spread. You must have received immune therapy, and your cancer treatment must not aim to cure the cancer.
- You must have a negative tuberculosis (TB) test within 30 days before starting the study, unless you meet one of the exceptions below.
- If you had the BCG vaccine against TB, a positive TB skin test is allowed if your QuantiFERON blood test is negative.
- Certain other positive or unclear TB tests are allowed only if you completed proper TB prevention treatment, have no TB symptoms or known exposure since treatment, and have a chest X-ray showing no active TB within 3 months before your first dose.
Who can't join
- Current thoughts of suicide, severe depression, a past suicide attempt, or a depression survey score above 20. Scores above 5 but below 20 require a mental health provider to confirm that your depression is stable. Drug or alcohol abuse within the past 6 months also rules you out.
- Past brodalumab treatment, an allergy or other reason you cannot take brodalumab or steroids, or a need for other medicines that lower immune system activity. Use of those other medicines within 28 days before starting also rules you out.
- Pregnancy, breastfeeding, plans to become pregnant, or not following the study's birth control rules. Patients assigned female at birth must use highly effective birth control during treatment and for at least 4 weeks afterward, unless they meet the study's exceptions.
- A long-term or current severe infection needing medicine through a vein; active hepatitis B, hepatitis C, or TB; untreated or partly treated inactive TB; or current or past Crohn's disease, which causes swelling in the digestive tract.
- Poor kidney function, serious heart disease, a heart attack, unstable chest pain, or stroke within the past 12 months. Certain abnormal liver tests or low blood cell counts also rule you out.
- Another health problem, heart test finding, or treatment that the study doctor thinks could make the study unsafe or make results hard to judge. A past autoimmune disease, where the immune system attacks healthy tissue, may also rule you out.
- Plans for more cancer treatment aimed at a cure, or participation in another treatment trial with study drugs received within 4 weeks before screening.
- A live-virus vaccine within 4 weeks before the first brodalumab dose.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * Ability to provide written informed consent by subject or guardian * Individuals \>18 years of age * Diagnosis of an irAE clinically suspected to be IL-17 mediated * Intent-to-treat or prior treatment with systemic steroids for irAE management * Histology-proven primary advanced or metastatic solid organ malignancy treated with immunotherapy. Patients being treated with curative intent are not eligible to enroll. * Subject has a negative test for tuberculosis during screening defined as either: negative purified protein derivative (PPD) (\< 5 mm of induration at 48 to 72 hours after test is placed) OR negative QuantiFERON test. Tuberculosis testing must be performed within 30 days prior to trial initiation. * Subjects with a positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative QuantiFERON test. * Subjects with a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or subjects with a positive or indeterminate QuantiFERON test are allowed if they have all of the following: no symptoms of tuberculosis (defined as fever, shortness of breath, cough or night sweats), documented history of a completed course of adequate prophylaxis (per local standard of care), no known exposure to a case of active tuberculosis after most recent prophylaxis, no evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of brodalumab. Exclusion Criteria: * Estimated creatinine clearance \< 40 mg/min * Active suicidal ideation or severe depression (as defined by the Diagnostic and Statistical Manual of Mental Disorders Version IV criteria (DSM-IV)) at the time of enrollment or a PHQ-9 score \> 20 * History of prior suicide attempts * PHQ-9 score greater \>5 and \< 20 without an established mental health provider who verifies stability in their depression * Current or prior drug or alcohol abuse within the past 6 months (as defined by the DSM IV) * In the opinion of the investigator, the patient requires additional immunosuppressive treatment (other than corticosteroids and brodalumab) * Known hypersensitivity or contraindication to brodalumab, corticosteroids or any components of brodalumab * Prior treatment with brodalumab * Pregnancy, breastfeeding, or use of a nonreliable method of contraception * For patients assigned female at birth: lack of willingness to use highly effective methods of birth control during treatment and for at least 4 weeks after the last dose of brodalumab (except if surgically sterile or at least 2 years postmenopausal, with postmenopausal status confirmed by Follicle-Stimulating Hormone (FSH) in the postmenopausal range). * Highly effective methods of birth control include: use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Oral contraceptive pills must be supplemented by a barrier method. * Patients planning to become pregnant while enrolled in the study and within 4 weeks after the last dose of brodalumab will not be permitted to enroll * Chronic or current severe infection requiring IV therapy * Evidence of active hepatitis B, C, or tuberculosis. * History of latent tuberculosis infection which is incompletely treated based upon local standard of care or which was never treated * History of or active Crohn's disease. * Myocardial infarction, unstable angina pectoris or stroke within the past 12 months prior to the first investigational product dose * Any concurrent medical condition or electrocardiogram (ECG) abnormality that, in the opinion of the investigator, could cause this study to be detrimental to the subject. * Any medical condition or treatment for a condition that, in the opinion of the investigator, might interfere with participation in the study or affect the reliability of clinician assessment or patient self-report * Other known clinically significant active medical conditions, such as: * Severe cardiovascular disease, including advanced heart failure (American Heart Association Stage D) * Aspartate aminotransferase (AST) and or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal or greater than 3 times the upper limit of normal in patients with liver metastases measured on at least two separate occasions * Direct bilirubin greater than or equal to 1.5 mg/dL in patients with or without liver metastases * Bone marrow insufficiency unrelated to the irAE (according to investigator judgment) with White Blood Cell (WBC) \<2000/mm3, absolute neutrophil count \<1500/ mm3, thrombocytopenia (platelet count) \<50,000/mm3, hemoglobin \< 8.0 g/dL * Plan to proceed with further curative intent treatment for cancer at the time of enrollment despite the presence of irAE * Participation in another therapeutic clinical trial and receipt of investigational drugs within 4 weeks before the screening visit * Previous diagnosis of an autoimmune disease or administration of immunosuppressants in a time frame that would impede interpretation of brodalumab administration * Planned use of immunosuppressive agents other than steroids (including infliximab, vedolizumab, tocilizumab etc.) or administration of such agents within 28 days of trial initiation * Administration of live-virus vaccines within 4 weeks before the first dose of brodalumab
Study sites (1)
NY
- Columbia University Irving Medical Center · New York, NY 10032Brian Henick, MD · Study contact · 212-305-5098 · bh2682@cumc.columbia.eduMore trials in New York