Accelerated Checkpoint Therapy for Any Steroid Dependent Patient With Brain Metastases

NCT04461418 | Terminated Phase 2 DMC

• 1 other identifier: IIT-0003
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain Metastases, Adult

Outcome Measures

Primary Outcomes (2)

• Intracranial and extracranial objective response rate

  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.

  24 weeks following enrolment of the last participant to study

• Time to initiation of therapy

  Defined as the time interval between first radiographic documentation of intracranial metastatic disease and initiation of systemic immunotherapy.

  24 weeks following enrolment of the last participant to study

Secondary Outcomes (3)

• Mortality analyses

  Upon completion of 12 month follow-up period for the final participant enrolled to the study.

• Patient-reported quality of life analysis

  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.

Study Arms (2)

Dexamethasone

ACTIVE COMPARATOR

Dose starting at 4 mg daily (for patients randomized to the Dexamethasone arm).

Drug: Glucocorticoid therapy

Prednisone

ACTIVE COMPARATOR

Dose starting at 25 mg/day (a calculation of equipotent steroid equivalencies will be used).

Drug: Glucocorticoid therapy

Interventions

Glucocorticoid therapy DRUG

The study intervention is defined as treatment with either prednisone or dexamethasone as palliative therapy for the control of neurological symptoms; patients with symptomatic brain metastases with a requirement for glucocorticoid therapy will be treated with an available, standard-of-care immune checkpoint inhibitor regimen.

Dexamethasone; Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• The following adequate organ function laboratory values must be met:
• Hematological:
• Absolute neutrophil count (ANC) \>1.0

You may not qualify if:

• 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.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead

Study Sites (1)

Cross Cancer Institute

Edmonton, Alberta, T6G1Z2, Canada

Location

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label, two cohort, permuted block randomization phase II study.

Study Record Dates

• First Submitted: July 3, 2020
• First Posted: July 8, 2020
• Study Start: March 30, 2021
• Primary Completion: September 23, 2023
• Study Completion: September 23, 2023
• Last Updated: June 27, 2025

Record last verified: 2025-06

Locations

CA (1)