An Interventional, Randomized Phase II Study Investigating the Efficacy of Immune Checkpoint Inhibitors While Corticosteroid Therapy is Required for Patients With Symptomatic Brain Metastases.
Overview
- Phase
- Phase 2
- Intervention
- Glucocorticoid therapy
- Conditions
- Brain Metastases, Adult
- Sponsor
- AHS Cancer Control Alberta
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Intracranial and extracranial objective response rate
- Status
- Terminated
- Last Updated
- 10 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with the following histologically confirmed diagnoses will be eligible for enrolment: malignant melanoma, non-small cell lung cancer and renal cell carcinoma and genitourinary carcinoma not-otherwise specified.
- •At the time of enrolment patients must have central nervous system metastases requiring corticosteroid therapy and have already started corticosteroid therapy.
- •Patients eligible for treatment with an available, standard-of-care immune checkpoint inhibitor regimen.
- •Patients with extracranial disease will be eligible for enrolment, however the presence of extracranial measurable disease is not a requirement for enrolment.
- •Patients must be 18 years of age or older.
- •Patients must be capable of providing consent to enrolment and willing to comply with study treatment and follow-up.
- •Patients with a performance status of ECOG 0-2 will be eligible for enrolment.
- •Measurable intracranial disease must be present according to RECIST 1.1 criteria.
- •Patients with hyperthyroidism or hypothyroidism but that are stable on hormone replacement will not be excluded.
- •Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes.
Exclusion Criteria
- •Known history of human immunodeficiency virus (HIV), active Hepatitis B or Hepatitis C. Testing for HIV, HBV or HCV is not mandatory for enrolment to study, but may occur at the discretion of the investigator.
- •Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- •Patients receiving non-steroid immunosuppressive agents (examples may include anti-TNF biologic agents, methotrexate, mycophenylate mofetil, tacrolimus) will be excluded from this study.
- •Known prior severe hypersensitivity to study drugs or any component in its formulations.
Arms & Interventions
Dexamethasone
Dose starting at 4 mg daily (for patients randomized to the Dexamethasone arm).
Intervention: Glucocorticoid therapy
Prednisone
Dose starting at 25 mg/day (a calculation of equipotent steroid equivalencies will be used).
Intervention: Glucocorticoid therapy
Outcomes
Primary Outcomes
Intracranial and extracranial objective response rate
Time Frame: 24 weeks following enrolment of the last participant to study
Objective response rate will be determined utilizing RECIST 1.1 criteria. Baseline staging diagnostic imaging (CT and/or MRI studies) will be performed in advance of beginning treatment and repeated 6 weeks following treatment initiation and at 12 week intervals thereafter.
Time to initiation of therapy
Time Frame: 24 weeks following enrolment of the last participant to study
Defined as the time interval between first radiographic documentation of intracranial metastatic disease and initiation of systemic immunotherapy.
Secondary Outcomes
- Patient-reported quality of life analysis(Upon completion of 12 month follow-up period for the final participant enrolled to the study.)
- Mortality analyses(Upon completion of 12 month follow-up period for the final participant enrolled to the study.)
- Assessment of treatment safety(Upon completion of 12 month follow-up period for the final participant enrolled to the study.)