Clinical Research Directory

Reducing the Incidence of Symptomatic Brain Metastases With MRI Surveillance

The purpose of this research is to see if monitoring the brain using magnetic resonance imaging (MRI) after radiation therapy will allow investigators to find cancer that has spread to the brain (brain metastases) before it causes symptoms.

A Phase II Study of Tucatinib and Ado-trastuzumab Emtansine (T-DM1) in Patients With HER2-positive Metastatic Solid Tumors and Metastases to Brain (TUCATEMEB)

To learn if the study drugs, tucatinib and adotrastuzumab emtansine (T-DM1), can help to control solid tumors that have spread to the brain.

Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases

This research study is studying stereotactic radiation (focused/pinpoint radiation that targets each individual tumor but not the surrounding brain) instead of whole-brain radiation (radiation targeting the entire brain) as a possible treatment for patients with small cell lung cancer and 1-10 brain metastases. The intervention involved in this study is: -Stereotactic (focused, pinpoint) radiation

Phase I Study of Fractionated Stereotactic Radiation Therapy

There is a lack of prospective trial data and consensus guidelines describing the use of Fractionated Stereotactic Radiation Therapy (FSRT) in the treatment of brain metastases. There has been no prospective dose escalation study performed to date to determine the maximum tolerated dose (MTD) in patients treated with FSRT. Prescription doses in the series described above ranged from 18 Gy to 42 Gy, delivered in 3 to 12 fractions. The results of this study will be used to plan future Phase II/III studies to determine the efficacy of different dose fractionation schedules of FSRT. The investigator team thus proposes a Phase I study to determine the feasibility and safety of FSRT in patients with brain metastases.

ctDNA-Guided Intraventricular Therapy for CNS Malignancies

This prospective, single-center study will evaluate whether cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) testing using the Belay Summit assay can improve the clinical management of patients with malignant gliomas or brain metastases from non-small cell lung cancer (NSCLC) or breast cancer who are suspected of having central nervous system (CNS) disease. Patients undergoing clinically indicated CSF evaluation will receive standard clinical testing, including CSF cytology and the Belay Summit ctDNA assay. Treatment decisions will remain at the discretion of the treating multidisciplinary neuro-oncology team. The primary objective is to evaluate 6-month clinical CNS progression-free survival (cCNS-PFS), with secondary objectives assessing safety and the association between CSF ctDNA dynamics and clinical outcomes. Exploratory proteogenomic analyses will be performed on residual CSF specimens when sufficient sample is available.

Stereotactic Radiosurgery Dose Escalation for Brain Metastases

This is a Phase I dose escalation and expansion trial. The purpose of this study is to determine the maximum tolerated dose of radiation received during stereotactic radiosurgery in patients with brain metastases who have never received radiation to the brain before.

Neurocognitive Functioning With Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases

This is a trial that evaluates the preservation of cognition and neuropsychiatric function following genu-sparing whole brain radiation in patients with brain metastases.

Ex Vivo Drug Response Evaluation for Next Generation Care of Brain Metastases

Pharmacoscopy refers to an ex vivo real-time drug sensitivity profiling platform that has been shown to be of value in the treatment of leukemia (Snijder et al. 2017) (Kornauth et al. 2022) and may help to identify novel treatment opportunities for brain tumors as well (Lee et al. 2022). The rationale for pharmacoscopy-based drug sensitivity testing on real-time patient biopsies or surgery material is multiple: measuring drug response and sensitivity directly in real-time patient material, overcomes the problem of limited molecular biomarkers for established targeted therapeutic options and can identify effective drugs even for non-targeted therapies such as chemotherapy. It can also identify hitherto unknown specific vulnerabilities of cancer cells. Furthermore, testing directly on patient material overcomes the limitations of patient-derived cell cultures, organoids, and patient xenografts, as their prolonged culture times risk cellular adaptations and clonal selection that alter drug sensitivity. Pharmacoscopy maintains the tumor cell composition, including bystander cells or tumor microenvironment, and limits cell culture to max 48 hours. Furthermore, pharmacoscopy measures drug responses on a single-cell and on a high-content level, uniquely allowing to measure the drug sensitivity of tumor cells, and allowing to compare it to the drug cytotoxicity on healthy cells from the same patient. This relative readout has previously been shown to be essential for the correct prediction of a clinical response in haematological malignancies (Snijder et al. 2017) (Kornauth et al. 2022). The aim of this study is to generate preliminary data regarding superiority of the personalized pharmacoscopy-guided approach compared to a standard non-pharmacoscopy-guided approach, in patients with brain metastases with an indication for surgery, and limited therapeutic systemic options according to the treating physician.

Pembrolizumab In Central Nervous System Metastases

This research study is studying Pembrolizumab as a possible treatment for this diagnosis for metastases in the central nervous system (brain and spinal cord).

Memory Avoidance Whole Brain Radiotherapy vs Hippocampal Avoidance Whole Brain Radiotherapy (Athena 2 Trial)

Participants in this research study have cancer that has spread to their brain, called brain metastases. One treatment for this type of cancer is called whole brain radiotherapy that stays away from a specific neurocognitive substructure, called the hippocampus, combined with medication to preserve cognitive function. This study compares that approach to another approach of whole brain radiotherapy that stays away from additional structures that are thought to have a role in cognitive function. Researchers want to see if there is a difference in the preservation of cognitive function between these two approaches.

Secondary BRain Metastases Prevention After Isolated Intracranial Progression on Trastuzumab/Pertuzumab or T-DM1 in Patients With aDvanced Human Epidermal Growth Factor Receptor 2+ brEast Cancer With the Addition of Tucatinib

Patients with advanced HER2+ breast cancer on maintenance trastuzumab/pertuzumab or T-DM1 with 1st or 2nd intracranial disease event (brain metastases) and stable extracranial disease will be enrolled. They will receive local therapy with stereotactic radiosurgery ± surgical resection if indicated followed by enrollment. Patients will continue standard of care trastuzumab/pertuzumab or T-DM1 with the addition of tucatinib. Hormone receptor positive patients requiring endocrine therapy should continue. Study treatment will continue until disease progression or intolerable side effects. Patients on trial with extracranial disease progression with stable intracranial disease should continue tucatinib into next line of therapy.

REMASTer: REcurrent Brain Metastases After SRS Trial

Randomized, post-market multi-center study investigating the efficacy of two sets of treatment algorithms in brain metastases (BM) patients at the time of first intervention for radiographic progression after stereotactic radiosurgery (SRS), with or without surgery.

Stereotactic Brain-directed Radiation With or Without Aguix Gadolinium-Based Nanoparticles in Brain Metastases

The purpose of this study is to determine whether AGuIX (Activation and Guidance of Irradiation by X-ray) gadolinium-based nanoparticles make radiation work more effectively in the treatment of patients with brain metastases that are more difficult to control with stereotactic radiation alone.

Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies

BDTX-4933-101 is a first-in-human, open-label, Phase 1/2 dose escalation, dose optimization and expansion study designed to evaluate the safety and tolerability of S241656 as monotherapy and in combination with other anti-cancer therapies in participants with selected advanced malignancies. The study population for the Dose Escalation part of the study comprises adults with recurrent advanced/metastatic non-small cell lung cancer (NSCLC), Gastrointestinal (GI) cancers, and other solid tumors harboring KRAS, HRAS, NRAS, BRAF, and/or CRAF (Rapidly Accelerated Fibrosarcoma (RAF1)) mutations or alterations. A dose optimization part in adults with NSCLC may follow the dose escalation phase if the sponsor, in consultation with the safety review committee, decides it is necessary to further characterize the optimal dose. However, the study may also proceed directly to the expansion phase. The study population for the Dose Expansion part of the study comprises adults with advanced/metastatic NSCLC with KRAS and/or BRAF mutations, and with Pancreatic Ductal AdenoCarcinoma (PDAC), ColoRectal Cancer (CRC), and Biliary Tract Cancer (BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations and alterations. All patients will self-administer S241656 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.

Allogeneic, Antigen-Presenting, GM-CSF-secreting, SV-BR-1-GM Whole Cell-Therapeutic Vaccine and Immunotherapy

This is a prospective, single-center, phase 1 basket trial that will evaluate the safety and feasibility of administering SV-BR-1-GM in combination with pembrolizumab to solid tumor oncology patients over nine cycles.

Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases

To determine the safety and efficacy of using the drug azeliragon combined with stereotactic radiosurgery. Specifically, to determine if this combination will lead to improved response in the brain (tumor shrinking in size) and overall tumor control (how long tumor remains controlled).

A Study of Stereotactic Radiosurgery (SRS) for People With Lung Cancer That Has Spread to the Brain

The purpose of the study is to see if stereotactic radiosurgery/SRS is an effective treatment for people with a new diagnosis of brain metastases from small cell lung cancer/SCLC.

Neurocognitive Decline in Patients With Brain Metastases

The phase I component of the study is to identify maximal tolerated dose (MTD). The phase II is to evaluate neurocognitive decline.

Stereotactic Radiosurgery Compared With Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) Plus Memantine for 5 or More Brain Metastases

Stereotactic radiosurgery (SRS) is a commonly used treatment for brain tumors. It is a one-day (or in some cases two day), out-patient procedure during which a high dose of radiation is delivered to small spots in the brain while excluding the surrounding normal brain. Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) is when radiation therapy is given to the whole brain, while trying to decrease the amount of radiation that is delivered to the area of the hippocampus. The hippocampus is a brain structure that is important for memory. Memantine is a drug that is given to help relieve symptoms that can be caused by WBRT, including problems with memory and other mental symptoms. Health Canada, the regulatory body that oversees the use of drugs in Canada, has not approved the sale or use of memantine in combination with WBRT to treat this kind of cancer, although they have allowed its use in this study.

Early [18F]-FDG PET Dynamic Analysis in Brain Metastases After Radiotherapy.

Various treatment options are available for brain metastases, depending on factors such as lesion site or number lesions. Radiotherapy is a commonly used treatment. Following stereotactic radiotherapy for brain metastases, a potential complication, namely brain radionecrosis, can occur subsequently. It is essential to differentiate between this radionecrosis and lesion recurrence in order to determine the appropriate treatment approach. Contrast-enhanced magnetic resonance imaging (MRI) is the most widely used technique for monitoring brain metastases. Therefore, patients undergo routine MRI at 3 months and during subsequent follow-ups, but if the lesion evolve and if distinguishing between recurrence and radionecrosis is challenging, an \[18F\]-FDG PET scan is then prescribed by oncologists or radiotherapists during follow-up consultations. As part of the standard patient management protocol, a 10-minute image acquisition begins after a 45-60 minutes wait following the radiotracer injection. A second image acquisition is then conducted 3-4 hours later. For both acquisitions, a low-dose X-ray scanner is synchronously coupled to allow attenuation correction of the PET images. Patient for whom a \[18F\]-FDG PET cerebral examination has been prescribed as part of the usual management of brain metastases will be eligible to the protocol. If the patient agrees to participate, an early imaging session is initiated immediately upon radiotracer injection, lasting 15 minutes in addition to the standard acquisition protocol.

Binimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis

This study evaluates the addition of stereotactic radiosurgery (SRS) to the combination of binimetinib + encorafenib + pembrolizumab in the treatment of BRAFⱽ⁶⁰⁰ mutation-positive melanoma with brain metastases (MBM).

Pembrolizumab and Lenvatinib in Patients With Brain Metastases From Melanoma or Renal Cell Carcinoma

This is a phase 2, Simon's 2-stage designed study with 2 cohorts of anti-PD-1/PD-L1 experienced patients with untreated brain metastases: 1) melanoma and 2) renal cell carcinoma (RCC).

MRI Biomarkers for Radiation-Induced Neurocognitive Decline Following SRS of Newly Diagnosed Brain Mets

Brain metastases are a source of much morbidity and mortality in adults with primary solid malignant tumors. With improvements in systemic therapy that prolong survival but have limited central nervous system penetration, patients with brain metastases are at increasing risk of developing and experiencing long-term side effects from treatment of brain metastases. The overarching goal of this study is to better understand the determinants of RT-associated changes in white and gray matter function and associated neurocognitive decline.

A Pilot Study to Assess the Clinical Utility of 18F-Fluciclovine (Axumin) PET-CT for Detecting True-versus Pseudo-Progression of Brain Metastases on Immunotherapy

To learn if 18F-Fluciclovine (Axumin) PET-CT scans can be used to better detect brain metastatic lesions in patients who are receiving immunotherapy.