Accelerated immunotherapy for patients with brain metastases on steroids

An Interventional, Randomized Phase II Study Investigating the Efficacy of Immune Checkpoint Inhibitors While Corticosteroid Therapy is Required for Patients With Symptomatic Brain Metastases.

This study is testing if immunotherapy can help people with brain metastases who are also taking steroids for their cancer treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AHS Cancer Control Alberta (Academic / other)
• Drugs / interventions: methotrexate, Immunotherapy
• Locations: 1 site (Edmonton, Alberta)
• Trial ID: NCT04461418 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of immunotherapy in patients with brain metastases who are also receiving corticosteroid therapy. Traditionally, patients on steroids have been excluded from immunotherapy trials due to concerns about immune suppression. The study aims to determine if immunotherapy can still be effective in this population, potentially providing a new treatment avenue for those with advanced cancer. Participants will receive glucocorticoid therapy alongside standard immune checkpoint inhibitors, with careful monitoring of their response.

Who should consider this trial

Good fit: Ideal candidates include adults with confirmed malignant melanoma, non-small cell lung cancer, or renal cell carcinoma who have brain metastases requiring corticosteroid treatment.

Not a fit: Patients with conditions not specified in the inclusion criteria or those unable to provide consent may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with brain metastases who require steroid therapy.

How similar studies have performed: While immunotherapy has shown success in various cancers, this specific approach for steroid-dependent patients with brain metastases is novel and has not been extensively tested.

Eligibility 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.

Where this trial is running

Edmonton, Alberta

• Cross Cancer Institute — Edmonton, Alberta, Canada (Recruiting)

Study contacts

• Study coordinator: John Walker

Conditions Brain Metastases, Adult