Improved Therapy Response Assessment in Metastatic Brain Tumors

Active, not recruiting

• Conditions: Brain Metastases
• Interventions: Diagnostic Test: Magnetic Resonance Imaging; Radiation: Stereotactic Radiosurgery; Drug: Ipilimumab, nivolumab or pembrolizumab

• Registration Number: NCT03458455
• Lead Sponsor: Oslo University Hospital

Brief Summary

TREATMENT is an observational study addressing the need for knowledge and adequate diagnostic biomarkers in the response assessment of patients with brain metastasis. Reliable response assessment will be highly relevant in the coming years given the introduction of next-generation cancer drugs, including immunotherapy. This project uses advanced Magnetic Resonance Imaging (MRI) and Vessel Architecture Imaging (VAI) to better understand the response to traditional stereotactic radiosurgery (SRS) and immunotherapy.

Secondary objectives include:

In patients with brain metastases, use advanced MRI and Vessel Architectural Imaging methods to reveal parameters of traditional, immunotherapeutic, and anti-angiogenic therapy response.

In patients with brain metastases, use advanced MRI and Vessel Architectural Imaging methods to compare results with traditional biomarkers.

Use existing infrastructure at Oslo University Hospital to standardize therapy monitoring.

In patients with brain metastases, use advanced MRI and Vessel Architectural Imaging methods to separate real tumor progression from treatment-induced pseudoprogression or radionecrosis

In patients with brain metastases, use advanced MRI and Vessel Architectural Imaging methods to assess whether anti-angiogenic drugs improve delivery of chemotherapy.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03-01
• Study First Submitted: 2018-03-02
• Study First Submitted QC: 2018-03-02
• Study First Posted: 2018-03-08
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-31
• Last Update Posted: 2023-11-01
• Primary Completion: 2024-07-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Participants must have histologically - or - radiographically confirmed metastatic disease from a primary non-small-cell lung cancer - or - metastatic melanoma.

• Participants must have measurable disease in the central nervous system (CNS), defined as at least one lesion that can be accurately measured in at least one dimension as ≥5 mm with MRI - or - compromise more than 30 image voxels on perfusion MRI to ensure adequate parametric statistical assessments. For a perfusion MRI resolution of 1.2x1.2x5mm, this equals a tumor volume of 0.2cubic centimeters (cc).

• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (Karnofsky ≥60%)

• Life expectancy of greater than 6 weeks

• Eligible for stereotactic radiosurgery

• Have normal organ functions per clinical guidelines

• Ability to understand and the willingness to sign a written informed consent document.

• Previously untreated asymptomatic brain metastases - or - progressive brain metastases after systemic therapy or prior local therapy such as radiation or surgery as defined by:

  1. Untreated measurable lesions in patients that have received surgery and/or SRS to one or more other lesions
  2. Residual or progressive lesions after surgery if asymptomatic
  3. Patients who have had prior whole-brain radiation therapy (WBRT) and/or SRS and then whose lesions have progressed are eligible. Lesions treated with SRS may be eligible if there is unequivocal evidence of progression
  4. Progression after prior systemic therapy.

Exclusion Criteria

• Participants who received major surgery must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a diagnosis of immunodeficiency or hypersensitivity to ipilimumab or any of its excipients (Cohorts C and D).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has a known additional malignancy that is progressing or requires active treatment.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Unable to undergo brain MRI

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
A	Magnetic Resonance Imaging	Patients with brain metastases from non-small cell lung cancer receiving stereotactic radiosurgery to selected lesions
C	Magnetic Resonance Imaging	Patients with brain metastases from non-small cell lung cancer receiving stereotactic radiosurgery to selected lesions + nivolumab or pembrolizumab
A	Stereotactic Radiosurgery	Patients with brain metastases from non-small cell lung cancer receiving stereotactic radiosurgery to selected lesions
D	Ipilimumab, nivolumab or pembrolizumab	Patients with brain metastases from malignant melanoma receiving stereotactic radiosurgery to selected lesions + ipilimumab, nivolumab or pembrolizumab
D	Stereotactic Radiosurgery	Patients with brain metastases from malignant melanoma receiving stereotactic radiosurgery to selected lesions + ipilimumab, nivolumab or pembrolizumab
E	Magnetic Resonance Imaging	Patients with brain metastases from non-small cell lung cancer receiving stereotactic radiosurgery to selected lesions + epidermal growth factor receptor (EGFR) inhibitors
B	Magnetic Resonance Imaging	Patients with brain metastases from malignant melanoma receiving stereotactic radiosurgery to selected lesions
C	Ipilimumab, nivolumab or pembrolizumab	Patients with brain metastases from non-small cell lung cancer receiving stereotactic radiosurgery to selected lesions + nivolumab or pembrolizumab
D	Magnetic Resonance Imaging	Patients with brain metastases from malignant melanoma receiving stereotactic radiosurgery to selected lesions + ipilimumab, nivolumab or pembrolizumab
B	Stereotactic Radiosurgery	Patients with brain metastases from malignant melanoma receiving stereotactic radiosurgery to selected lesions
C	Stereotactic Radiosurgery	Patients with brain metastases from non-small cell lung cancer receiving stereotactic radiosurgery to selected lesions + nivolumab or pembrolizumab
E	Stereotactic Radiosurgery	Patients with brain metastases from non-small cell lung cancer receiving stereotactic radiosurgery to selected lesions + epidermal growth factor receptor (EGFR) inhibitors

Primary Outcome Measures

Name	Time	Method
Treatment Response	18 months	Radionecrosis, pseudoprogression or tumor progression by Response Assessment in Neuro-Oncology Criteria (RANO) or histology, or radiographic/clinical progression free survival

Secondary Outcome Measures

Name	Time	Method
Overall survival	5 years	Overall survival

Trial Locations

Locations (1)

Oslo University Hospital; 🇳🇴 Oslo, Norway