Accelerated Checkpoint Therapy for Any Steroid Dependent Patient With Brain Metastases
Keywords
Abstract
Dates
Last Verified: | 06/30/2020 |
First Submitted: | 07/02/2020 |
Estimated Enrollment Submitted: | 07/02/2020 |
First Posted: | 07/07/2020 |
Last Update Submitted: | 07/02/2020 |
Last Update Posted: | 07/07/2020 |
Actual Study Start Date: | 08/31/2020 |
Estimated Primary Completion Date: | 08/31/2024 |
Estimated Study Completion Date: | 08/31/2025 |
Condition or disease
Intervention/treatment
Drug: Glucocorticoid therapy
Phase
Arm Groups
Arm | Intervention/treatment |
---|---|
Active Comparator: Dexamethasone Dose starting at 4 mg daily (for patients randomized to the Dexamethasone arm). | |
Active Comparator: Prednisone Dose starting at 25 mg/day (a calculation of equipotent steroid equivalencies will be used). |
Eligibility Criteria
Ages Eligible for Study | 18 Years To 18 Years |
Sexes Eligible for Study | All |
Accepts Healthy Volunteers | Yes |
Criteria | Inclusion Criteria: 1. 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. 2. At the time of enrolment patients must have central nervous system metastases requiring corticosteroid therapy and have already started corticosteroid therapy. 3. Patients eligible for treatment with an available, standard-of-care immune checkpoint inhibitor regimen. 4. Patients with extracranial disease will be eligible for enrolment, however the presence of extracranial measurable disease is not a requirement for enrolment. 5. Patients must be 18 years of age or older. 6. Patients must be capable of providing consent to enrolment and willing to comply with study treatment and follow-up. 7. Patients with a performance status of ECOG 0-2 will be eligible for enrolment. 8. Measurable intracranial disease must be present according to RECIST 1.1 criteria. 9. Patients with hyperthyroidism or hypothyroidism but that are stable on hormone replacement will not be excluded. 10. 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. 11. Patients of childbearing / reproductive potential should use adequate birth control methods, as defined by the investigator, during the study treatment period and for a period of 30 days after the last dose of study drug. 12. Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial. 13. The following adequate organ function laboratory values must be met: Hematological: - Absolute neutrophil count (ANC) >1.0 - Platelet count >100 - Hemoglobin >90 mg/dL Renal: - Serum creatinine <2x ULN Hepatic: - Total serum bilirubin <1.5x ULN - AST and ALT <3x ULN Coagulation: - International Normalized Ratio (INR) <1.5x ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants) - Activated Partial Thromboplastin Time (aPTT) <1.5x ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants) Exclusion Criteria: 1. 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. 2. 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. 3. Patients receiving non-steroid immunosuppressive agents (examples may include anti-TNF biologic agents, methotrexate, mycophenylate mofetil, tacrolimus) will be excluded from this study. 4. Known prior severe hypersensitivity to study drugs or any component in its formulations. |
Outcome
Primary Outcome Measures
1. Intracranial and extracranial objective response rate [24 weeks following enrolment of the last participant to study]
2. Time to initiation of therapy [24 weeks following enrolment of the last participant to study]
Secondary Outcome Measures
1. Mortality analyses [Upon completion of 12 month follow-up period for the final participant enrolled to the study.]
2. Patient-reported quality of life analysis [Upon completion of 12 month follow-up period for the final participant enrolled to the study.]
3. Assessment of treatment safety [Upon completion of 12 month follow-up period for the final participant enrolled to the study.]