Clinical Research Directory

A Phase II Clinical Study of Utidelone and Bevacizumab With or Without Etoposide in Patients With Brain Metastases From Malignant Solid Tumors

Brain metastasis represents one of the worst prognostic outcomes in advanced malignant tumors. Approximately 10% to 40% of patients with solid tumors develop brain metastases, a incidence rate significantly higher than that of primary malignant brain tumors. Over 80% of patients present with multiple brain metastases at diagnosis, often precluding surgical intervention. Brain metastases typically occur in the late stages of cancer. Patients have often received multiple prior therapies and developed resistance to first- and second-line drugs, leaving limited pharmacological options. The rapid growth of intracranial tumors poses an immediate threat to life. Consequently, radiotherapy and surgery currently form the cornerstone of clinical management for these patients. Thus, developing effective systemic therapies is an urgent and unmet medical need . Utidelone, a new-generation epothilone anticancer agent, has demonstrated good efficacy and safety. Previous studies indicate that utidelone achieves higher concentrations in most tissues, including the brain, compared to plasma, suggesting its ability to readily cross the blood-brain barrier . Furthermore, a Phase III clinical trial in metastatic breast cancer showed that utidelone in combination with capecitabine significantly improved the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared to capecitabine alone in patients previously treated with anthracyclines and taxanes . A separate Phase II study demonstrated that bevacizumab combined with carboplatin achieved a central nervous system objective response rate (CNS ORR) of 63%, with a median PFS of 5.62 months and a median OS of 14.1 months in breast cancer patients with brain metastases . Regarding safety, utidelone has a relatively low incidence of adverse reactions aside from peripheral neurotoxicity . Based on this evidence, this proposed study aims to evaluate the efficacy and safety of utidelone and bevacizumab, combined with etoposide for breast cancer cohorts or without etoposide for lung cancer cohorts, in patients with malignant tumor brain metastases.

18F-FLUC PET/MR in Patients With Brain Mets

The goal of this clinical trial is to use new imaging methods to help in finding out whether the imaging shows that there is a tumor in people with a brain metastasis. The main question it aims to answer is whether positron emission tomography (PET) and magnetic resonance imaging (MRI) find cancerous tissue better than other types of imagining. Participants will undergo a single PET/MRI scan, followed by a separate MRI scan with a tracer. Study participation will last about 3 hours.

Stereotactic Radiotherapy in Oligometastatic Brain Disease: a Randomised Phase III Study Comparing Hypofractionated Stereotactic Radiation Therapy (3*10 Gy) to the Historical Single-dose Radiosurgery (1*20 to 25 Gy) With Medico-economic Evaluation.

Brain metastases (BM) are a common systemic cancer manifestation which incidence increases. Therapeutic options include whole-brain radiotherapy (WBRT), surgery, and stereotactic radiosurgery (SRS). The concept of "oligometastatic" cerebral disease (oligoBM) has emerged and led to consider alternative approaches. The main challenge is to preserve neurological function and independence the longest as possible. Stereotactic radiotherapy (SRT) has emerged as an alternative treatment modality for selected oligoBM patients. It allows to achieve the balance of tumour destruction and normal tissue preservation by precisely and accurately delivering a very high dose of radiation in one (SRS) or a few (HSRT) fractions to a limited, well-defined volume. However, no standard exists for decision-making between SRS and HSRT and this important question is being discussed in the recent literature. HSRT appears particularly interesting, assuming the patient convenience of few fractions, the normal tissue sparing achieved through focal irradiation, and the improved normal tissue tolerance of high dose radiation through fractionation. Common adverse effects of SRT are rare but can occasionally be serious, notably radionecrosis that may induce neurological deficits in patients. Although SRS is often less well-tolerated, it remains the mainstay of treatment. To investigators knowledge, SRS and HSRT have not been prospectively compared.

Feasibility of a Cognitive Stepped Care Program for Adults With Brain Metastases

Background: Cognitive symptoms are common and often severe in patients with brain metastases, significantly impacting their quality of life and ability to manage cancer care. Currently, there is no standard approach for routinely assessing and managing these symptoms in oncology clinics. Objective: This study aims to evaluate the feasibility, acceptability, and preliminary efficacy of the Cognitive Stepped Care Program (CSCP) in a Brain Metastases Clinic. Methods: This is a prospective, mixed-methods feasibility study involving patients with brain metastases, their caregivers, and clinic staff. Patients will undergo routine cognitive symptom screening using a standardized tool. Based on symptom severity, they will receive tiered interventions ranging from no support, to education materials, to computerized cognitive testing with individualized debrief, with group strategy training and/or neuropsychological consultation, as needed. Patients will complete questionnaires before and after the intervention regarding their symptoms and quality of life. Patients, caregivers and staff will provide their feedback about the intervention through questionnaires and interviews. Outcomes: Primary outcomes include feasibility and acceptability of the CSCP. Secondary outcomes include preliminary changes in cognitive symptoms, self-efficacy, and quality of life. Significance: This study will inform the potential integration of a structured cognitive support program into standard care for patients with brain metastases and may provide a model for similar interventions in other oncology settings.

Sacituzumab Tirumotecan Plus Third-Generation TKI With/Without Radiotherapy for EGFR-Mutant NSCLC Brain Metastases

This is a prospective, open-label, multi-center, single-arm clinical trial

Evaluation of Neoadjuvant Stereotactic Radiosurgery (SRS) and Multi-fraction SRS Alone for the Treatment of Large Brain Metastases

The prospective, two-arm, randomized, controlled, multicentric phase III RENESANS trial is designed to compare the efficacy and safety of neoadjuvant stereotactic radiosurgery (Neo-SRS) versus multi-fraction stereotactic radiosurgery (mfSRS) in patients with large brain metastases, with the primary objective of evaluating the incidence of central nervous system composite events.

Elimination of PTV Margins Based on MRI-guided Adaptive Stereotactic Radiotherapy for Non-small Cell Lung Cancer With Brain Metastasis

This study aims to explore the safety and efficacy of eliminating the planning target volume (PTV) margins based on MRI-guided adaptive stereotactic radiotherapy for non-small cell lung cancer (NSCLC) patients with brain metastasis.

Efficacy of the RayerKnife X Stereotactic Radiotherapy System in the Treatment of Brain Metastases

The goal of this clinical trial is to evaluate the efficacy of stereotactic radiotherapy in the treatment of brain metastases. The main question it aims to answer is: Did stereotactic radiotherapy improve LC rate in the treatment of brain metastases? Participants will be recorded for local control rates during follow-up.

Sacituzumab Govitecan Combined With Head Radiotherapy for Her2-negative Breast Cancer Brain Metastases

The incidence of brain metastasis of Her2-negative breast cancer is high, which seriously affects the prognosis of patients.The treatment of brain metastasis of Her2-negative breast cancer is still tricky. The local efficacy of head radiotherapy for breast cancer brain metastases is remarkable, and systemic tumor progression in patients with brain metastases is the main reason for treatment failure. Sacituzumab Govitecan is the only Trop-2 antibody-coupled drug (ADC) approved for the treatment of unresectable locally advanced or metastatic Her2-negative breast cancer. However, the objective remission rate of Sacituzumab Govitecan for intracranial metastatic lesions has not been satisfactory. This study is an open, uncontrolled phase II clinical study to observe the efficacy and safety of Sacituzumab Govitecan combined with intracranial radiotherapy in the treatment of patients with brain metastases from Her2-negative breast cancer, in order to find a more effective treatment method.

Brain Metastasis Development Mechanism in BCBM Patients

This study is the experimental study for brain metastasis development mechanism in patients with breast cancer with brain metastasis

SHR-A1921 Combined With Bevacizumab in Triple-negative Breast Cancer With Brain Metastases

This is a phaseⅡ, single-arm study evaluating the efficacy and safety of SHR-A1921 Combined with Bevacizumab in Triple-negative Breast Cancer with Brain Metastases

A Prospective Study of the Impact of Hippocampal Avoidance During Whole Brain Radiotherapy on Neurocognitive Function Decline

Whole brain radiotherapy (WBRT) has long been a practical and effective therapeutic modality for various settings of management in radiation oncology. For example, the indications for WBRT should include brain metastasis or metastases, the setting of prophylactic cranial irradiation (PCI) used mainly for patients with limited-stage small cell lung cancer, and even some patients with extensive-stage small cell lung cancer. The rationales for WBRT are essentially based on that it can target both microscopic and gross intracranial disease. In addition to providing rapid alleviation of neurologic symptoms and enhanced intracranial disease control, WBRT might also prolong the time to develop neurocognitive function (NCF) decline. However, paradoxically NCF decline can also occur due to a sequel of WBRT. In terms of the time course of WBRT-induced NCF decline, it might vary considerably according to the specific domains which are selected to be measured. Early neurocognitive decline occurs within the first 1 - 4 months after WBRT for brain metastases. The domains of early neurocognitive decline principally involve verbal and short-term memory recall. Since several decades ago, it has been understood that hippocampus plays an essential role in memory function. Not little evidence supports that radiation-induced damage to hippocampus should be strongly associated with NCF impairment. Furthermore, several studies have shown that isodose distribution in hippocampus is closely related to neurocognitive function in patients with benign or low-grade brain tumors. As a consequence, it is hypothesized that conformal hippocampal sparing during the course of WBRT (HS-WBRT) might provide significant preservation in terms of cognitive function. This prospective cohort study aims to explore and evaluate the impact of the delivery of HS-WBRT on the pattern of NCF change and the extent of NCF decline in patients receiving prophylactic or therapeutic WBRT. As compared with previous related and relevant studies, it will also be investigated whether neurocognitive functional preservation can be achieved via the integration of hippocampal sparing with the course of WBRT.

Hippocampal-Sparing Prophylactic Cranial Irradiation in Pathologically Nodal Positive Non-Small-Cell Lung Cancer

Background. During the clinical course of patients with locoregionally advanced non-small-cell lung cancer (LA-NSCLC) who have undergone aggressive treatment, brain metastasis (BM) is a frequent seen pattern of disease relapse, which cannot be ignored. It still remains unresolved whether prophylactic cranial irradiation (PCI) via whole brain radiotherapy (WBRT) should be recommended for NSCLC patients with stage III or pathologically nodal positive disease. Actually, PCI would significantly decrease the incidence of BM; however, potential WBRT-related neurocognitive function (NCF) sequelae are indeed a concern, which has made PCI seldom applied in clinical practice. In terms of the time course of WBRT-induced NCF decline, it might vary considerably according to the specific domains which are selected to be measured. Early neurocognitive decline principally involve impairments of episodic memory, which has been significantly associated with functions of the hippocampus. This study thus aims to explore the impact of PCI on the subsequent risk of developing BM and the multi-domain neurobehavioral functions in our eligible patients. Methods. Potentially eligible subjects are postoperative NSCLC patients with a status of pathologically nodal metastasis (pN+). Patients randomly assigned to the PCI arm will undergo the course of hippocampal-sparing PCI after they complete the fourth course of adjuvant platinum-based chemotherapy. Radiotherapy dose will be 3000 cGy in 15 fractions during three weeks. Except for the administration of hippocampal-sparing PCI, patients assigned to the observation arm should receive the same baseline and follow-up brain imaging examinations and neurocognitive assessments as those in PCI arm. Accordingly, a battery of neuropsychological measures, which includes 7 standardized neuropsychological tests (e.g., executive functions, verbal \& non-verbal memory, working memory, and psychomotor speed), is used to evaluate neurobehavioral functions for our registered patients. Expected results. This randomized controlled study aims to verify that the incidence of BM still can significantly be reduced by hippocampal-sparing PCI; additionally, NCF preservation regarding neurobehavioral assessments might also be achieved by hippocampal-sparing PCI as compared with the observation arm without PCI. No matter what the final results present, it is believed that this randomized controlled trial (RCT) will provide us solid evidence concerning the exact value of hippocampal-sparing PCI in our patient setting.