Active clinical trials for "Meningeal Carcinomatosis"

Treatment of non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) mutation is mainly based on tyrosine kinase inhibitors (TKIs) targeting EGFR. 1st or 2nd generation inhibitors have been shown to be superior to chemotherapy in terms of Progression-Free Survival (PFS) when used as 1st line treatment. In case of progression at several metastatic sites, systemic treatment will be considered and will depend on the presence of the TKI resistance mutation, the T790M mutation. In the presence of the T790M mutation, osimertinib is superior to chemotherapy in terms of progression-free survival, while in the absence of the T790M mutation, platinum salt chemotherapy is recommended. In case of local progression, treatment of the site in progression by radiotherapy and/or surgery is considered. As these local treatments can cause long-term adverse effects, systemic treatments are increasingly being considered in this indication. Brain and leptomeningeal metastases are the most frequent isolated site of progression in EGFR mutated patients treated with TKI. The high frequency of isolated cerebral and leptomeningeal progression is a consequence of the lower diffusion of 1st and 2nd generation TKIs in the central nervous system (CNS). Osimertinib is a 3rd generation TKI that has the particularity of overcoming the T790M mutation and having greater brain penetration than 1st or 2nd generation TKIs, which could make it an attractive therapeutic option in the event of brain progression or leptomeningeal progression. However, its efficacy in patients with cerebral or leptomeningeal metastases is still poorly understood.

The investigators are doing this study to find out whether proton craniospinal radiation therapy (proton CSI) or partial photon radiation therapy is more effective at preventing leptomeningeal metastasis from worsening. The proton CSI targets the entire space containing the CSF, brain, and spinal fluid. The partial photon radiation therapy treats only areas where the patient is having symptoms, such as the entire brain or part of the spine. The investigators also want to find out if proton CSI improves the symptoms patients may be experiencing because of the leptomeningeal metastasis. In addition, the investigators will compare the side effects of proton CSI and partial photon therapy. Patients undergoing proton beam RT will receive their treatment at the New York Proton Center in New York, NY. As part of the New York Proton Consortium, MSK has contracted for its faculty to treat patients at the New York Proton Center. If it is unfeasible for patients to get treated at NYPC, patients will have the decision to get treated at ProCure in Summerset, NJ.

The goal of this clinical trial is to evaluate the efficacy of tucatinib and capecitabine in combination with intra-cerebrospinal fluid (CSF) trastuzumab on overall survival rate at 12 months in HER2-positive metastatic breast cancer (MBC) patients with proven leptomeningeal evolution and requiring intrathecal therapy.

Leptomeningeal metastasis (LM) is a complication of advanced non-small cell lung cancer (NSCLC). The incidence of LM in NSCLC patients is around 3-5 %, reaching 9.4 % of those with an epidermal growth factor receptor (EGFR) mutation. Generally, the efficacy of systemic treatment for LM is limited due to the blood-brain barrier. Osimertinib has a high central nervous system penetration rate, making it the preferred first-line treatment for EGFR-mutant NSCLC. Previous studies indicated that osimertinib had shown promising efficacy in pretreated patients harboring EGFR mutations and LM. However, intracranial disease progression eventually develops, and the prognosis of patients with LM progression after osimertinib is poor. Recently, intrathecal chemotherapy with pemetrexed (IP) was reported to be an alternative treatment in patients with NSCLC and LM. The results from a phase I/II trial examining the efficacy and safety of IP in patients with EGFR-mutant NSCLC after the failure of previous TKI, and 83% of study enrollees received osimertinib before IP. The clinical response rate was 84.6%, and the median overall survival was 9.0 months. Despite initial promising efficacy, further trials are needed to verify these results. Therefore, the investigators plan to conduct a prospective study to examine the safety and effectiveness of IP combined with EGFR-TKI for patients with EGFR mutant NSCLC after osimertinib failure.

Leptomeningeal metastasis is a rare but serious complication to cancer, with a grave prognosis. No efficient treatment exists. Recent data suggest that craniospinal radiotherapy lead to superior survival and CNS control compared to focal photon radiotherapy. We want to offer Danish patients the new treatment, but within a protocol, as this is new data with an new treatment principle

A prospective, open-label, multi-center, single-arm study of Almonertinib combined With Bevacizumab for EGFR-mutant NSCLC patients with leptomeningeal metastasis.

This is an open-label Phase 3 study to see if ANG1005 can prolong survival compared to a Physician Best Choice control in HER2-negative breast cancer patients with newly diagnosed leptomeningeal disease and previously treated brain metastases.

This study uses bi-specific antibody (HER2Bi) armed activated T-cells (HER2 BATs) to target breast cancer cells that have metastasized to the membranes surrounding the brain and spinal cord. This is known as leptomeningeal metastases. Two doses will be evaluated in order to determine a safe dose. Study treatment includes a test dose of HER2 BATs followed by 8 weekly infusions of HER2 BATs at the assigned dose level. Before, during and after study treatment, participants will be monitored objectively by brain MRIs and clinically through physical and neurological exams, and blood and cerebrospinal fluid will be collected to evaluate immune responses.

Subject's are being asked to take part in this study because he or she has a type of cancer that has spread to the meninges (tissues that cover the brain and spinal cord). There is no known effective treatment for this specific disease or the subject has received all of the treatments that are known to work for his or her specific disease without success. Currently, there is no other effective treatment for this type of cancer. The purposes of this study are: to determine the highest dose of gemcitabine, an anti-cancer drug, that can safely be given directly into the spinal fluid of children and adults whose cancer no longer responds to standard treatment; to find out what effects (good and bad) gemcitabine has when given directly into the cerebrospinal fluid (called intrathecal administration) in children and adults with neoplastic meningitis (cancer that has spread to the lining of the brain and spinal cord); to determine if gemcitabine is beneficial to the patient; to understand how gemcitabine is handled by the body after intrathecal administration.

The purpose of this trial is to test the safety and tolerance of the combination therapy with cytarabine, lomustine and radiotherapy in patients with leptomeningeal metastasis from malignant melanoma.