Clinical Research Directory

Efficacy of Laser Interstitial Thermal Therapy in Young Persons With Low-grade Glioma

This study aims to evaluate the efficacy of Laser Interstitial Thermal Therapy (LITT) in treating recurrent or progressive, low-grade gliomas (LGG) in pediatric, adolescent and young adult patients.

Trametinib and Everolimus for Treatment of Pediatric and Young Adult Patients With Recurrent Gliomas (PNOC021)

This phase I trial studies the side effects and best dose of trametinib and everolimus in treating pediatric and young adult patients with gliomas that have come back (recurrent). Trametinib acts by targeting a protein in cells called MEK and disrupting tumor growth. Everolimus is a drug that may block another pathway in tumor cells that can help tumors grow. Giving trametinib and everolimus may work better to treat low and high grade gliomas compared to trametinib or everolimus alone.

Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas

This phase II trial studies how well de-escalating the drugs dabrafenib and trametinib works in treating patients with low-grade gliomas that have a BRAF V600 gene mutation. Dabrafenib and trametinib are in a class of medications called kinase inhibitors. They work by blocking the action of abnormal proteins that signals tumor cells to multiply. This helps stop the spread of tumor cells. This trial may help doctors determine the best dosing strategy for patients who have received dabrafenib and trametinib for 12-24 months: Either stopping dabrafenib and trametinib completely or slowly reducing the dose for an additional 6 months.

DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)

This is a 2-arm, randomized, open-label, multicenter, global, Phase 3 trial to evaluate the efficacy, safety, and tolerability of tovorafenib monotherapy versus standard of care (SoC) chemotherapy in participants with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring first-line systemic therapy.

A Study to Assess a Medicine Called Tovorafenib in Japanese Children and Young Adults With Brain Tumours

The purpose of this study is to evaluate safety and the way the body absorbs, distributes and gets rid of the study drug tovorafenib in the body in Japanese children, adolescents and young adults with specific brain tumours. This includes how the drug is absorbed, distributed and eliminated from the body (called pharmacokinetics). The study will also test how well the drug works to shrink brain tumours. In this study, all participants will receive tovorafenib orally once weekly. There will be four periods in this study: 1. Screening period (up to 4 weeks): Participants will be evaluated to determine if they can take part in the study, requiring at least one visit to the study centre. 2. Treatment period (up to 24 months): All eligible participants will receive tovorafenib. This requires five visits for the first 2 months (Cycle 1 and Cycle 2) followed by one visit every month (at the start of each treatment cycle). Participants will receive the first oral dose of tovorafenib on Day 1 of Cycle 1 at the study clinic. After Day 1, participants will need to take tovorafenib once weekly on Day 8, Day 15 and Day 22. Participants will be required to come to the study clinic in person at least five times for Cycle 1 and Cycle 2. In addition, participants will have one remote visit (telephone call) during Cycle 1. After Cycle 2, only one in-person clinic visit is required at the start of each treatment cycle. A participant will stop treatment if their disease gets worse, if treatment has a harmful effect, or if they do not want to take part in the study anymore. 3. End-of-Treatment Safety Follow-Up (30 days): Participants will have a clinic visit 30 days after stopping treatment to check their health. 4. Long-Term Follow-Up (up to 2 years): Participants will be monitored every 3 months unless they start a new anti-cancer treatment or leave the study. During the study, participants will undergo various health measurements and observations, including blood sampling and urine collections. Each participant will be in this study for up to approximately 4 years. Tovorafenib will be provided to participants who tolerate it for as long as their disease does not progress. Once tovorafenib becomes approved and commercially available in Japan, participants may transition to the commercial drug for continued treatment. A participant may withdraw consent to participate at any time.

A Study of Avutometinib for People With Solid Tumor Cancers

The purpose of this study is to find out whether avutometinib is a safe treatment for advanced or recurrent solid tumor cancers in children and young adults. Researchers will look for the highest dose of avutometinib that is safe and cause few or mild side effects.

Niraparib In Recurrent IDH 1/2 Gliomas

This is a randomized, two-arm, open-label, phase 0 trial to assess intratumoral pharmacokinetics and pharmacodynamics of niraparib in subjects with progressive IDH1 or IDH2 mutant glioma. \- This research study involves an experimental treatment called Niraparib.

A Living Tissue Bank of Patient-Derived Organoids From Glioma Tumors

There is a high medical need to improve treatment outcome for high-grade and low-grade glioma since no curative treatment is available. To achieve this goal, a broader understanding is needed of the causes of inter-and intratumoral heterogeneity; glioma dedifferentiation and invasion; the major determinants of malignancy and treatment failure in glioma patients. Patient-derived organoid (PDOs) of high-grade gliomas and low-grade gliomas will be used to identify the mechanisms that underlie this malignant behaviour and treatment resistance. This insight may be used to develop patient avatars to simultaneously test multiple new treatment modalities that are predictive for survival and quality of life of glioma patients.

Rehabilitation and Longitudinal Follow-up of Cognition in Adult Lower Grade Gliomas

Patients with glial brain tumors have increasingly improved outcomes, with median survival of 5-15 years. However, the treatments, including surgery, radiation, and chemotherapy, often lead to impaired attention, working memory, and other cognitive functions. These cognitive deficits frequently have significant impact on patient quality of life. Although currently, there is no established standard of care to treat cognitive deficits in brain tumor patients, standard cognitive rehabilitative treatments have been developed for those with traumatic brain injury and stroke. However, the feasibility and efficacy of these cognitive treatments in individuals with brain tumors remains unclear.

Evaluation of 18F-Fluciclovine Positron Emission Tomography - Magnetic Resonance Imaging (PET-MRI) in LGG

The purpose of this study is to see if 18F-Fluciclovine (Axumin®) is useful and safe in the management of children with Low Grade Gliomas (LGG). Imaging with 18F-Fluciclovine PET-MRI will be performed prior to initiation of therapy for LGG, and then 3 months, and 1 year after starting therapy. Changes in 18F-Fluciclovine uptake will be compared to changes in MRI measurements at 3 months and 1 year as compared to baseline.

HOBSCOTCH-CA (HOme-Based Self-management and COgnitive Training CHanges Lives in Brain CAncer)

The purpose of this study is to assess the ability of the home-based intervention, HOBSCOTCH-CA, to improve the quality of life and cognitive function in Service Members, Veterans and civilians who are survivors of brain cancer or a brain tumor (CA participants). This study will also assess the ability of the HOBSCOTCH-CA program to improve quality of life in caregivers of patients with brain cancer/tumor and to reduce caregiver burden. Enrolling with a Caregiver is optional for CA participants. Investigators will compare two groups of CA participants and their Caregiver (enrolling with a Caregiver is optional): one who receives HOBSCOCTCH-CA immediately (Group 1) and another group that will receive HOBSCOTCH-CA (Group 2) after a 3-month waiting period. Participants will be in the study for about 6 months total. HOBSCOTCH-CA involves 45 to 60 minute one on one virtual sessions with a certified Cognitive Coach including a "pre" program session and 8 weekly sessions thereafter. Participants will learn about problem solving therapy and mindfulness or relaxation training. CA participants are asked to do short homework assignments and keep a brief daily diary on a smart phone app. All participants complete study questionnaires or surveys at enrollment, 3 months later and at 6 months (at the end of the study).

FCN-159 Monotherapy Versus Chemotherapy by Investigator's Choice in Pediatric Low-grade Glioma Patients With BRAF Alteration

An open-label, randomized, multi-center phase III clinical study: Aim to evaluate the efficacy and safety of FCN-159 monotherapy versus the treatment by investigator's choice in patients with pediatric low-grade glioma harboring KIAA1549-BRAF fusion or BRAF V600E mutation

Pilot Study of Vinblastine and Tovorafenib in Pediatric Patients With Recurrent/Progressive RAF Altered Low Grade Gliomas

This is a Pilot, multicenter, open-label study of patients less than or equal to 25 years, with recurrent or progressive LGG harboring a CRAF or BRAF alteration, including BRAF V600 mutations and KIAA1549: BRAF fusions. Patients with BRAF or CRAF alterations will be identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly certified laboratories. The study will be conducted in two sequential phases: Phase A: A Feasibility (combination dose finding) phase, followed by Phase B: An Efficacy phase. The maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of the combination as determined in Phase A would be the dose used in Phase B. The patients on Phase A who were below the MTD/RP2D would be eligible for intra-patient dose escalation to MTD/RP2D subject to criteria outlined later

A Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors

This is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of Type II RAF (tovorafenib) in pediatric participants with low-grade glioma or advanced solid tumors. Qualifying genomic alterations will be identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly certified laboratories prior to enrollment into any of the arms. The study will consist of a screening period, a treatment period, a long-term extension phase, end of treatment (EOT) visit(s), a safety follow-up visit, and long-term follow-up assessments.

FG001 in Subjects with Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery

In neurosurgery both the diffusely infiltrated gliomas of the brain as well as the border towards healthy tissue in the meninges is a challenge. For the high-grade contrast enhanced gliomas fluorescent drugs like Gliolan have been used in several years and proved its clinical value. For non-contrast enhanced gliomas, like low-grade glioma, no such drug exist. The transition zone towards healthy non-tumor cell infiltrated brain in such low-grade gliomas is extremely difficult but for these patients their prognosis depends on the amount of non-healthy tissue left behind. Also, in benign tumors as meningioma the complete resection including infiltrated meninges is of importance for the cure of the disease. None of the existing fluorescent drug is useful or approved for these tumors.. Hence a medicinal product that will fulfil the criteria for a safe and reliable fluorescent drug to guide the surgery to the boundaries of the infiltration with tumor cells is highly warranted.

Monitoring of Patients With Low-grade Gliomas Using Circulating miRNA

With around 3,400 cases per year in France, diffuse gliomas are the most common primary tumours of the central nervous system. Their grade varies from 2 to 4. Whatever the grade, their prognosis is poor, because tumour recurrence is systematic, because no personalised medicine is available for the treatment of these cancers, and because the tools for monitoring recurrence are imperfect. Treatment of diffuse gliomas is based on removal of as much of the tumour as possible, whatever its grade. Surgery is followed by radiotherapy and chemotherapy depending on the grade and quality of the excision. In the event of recurrence, the patient may be offered second-line chemotherapy or further surgery. During and after treatment, patients are regularly monitored by MRI in order to detect any recurrence as early as possible and propose a new treatment. However, for grade 2 and 3 gliomas, MRI monitoring is imperfect because it cannot detect tumour recurrence at an early stage. Initiation of new treatment at the time of recurrence, which is inevitable, is therefore often delayed, which is harmful for patients. It is therefore vital to identify a reliable, easy-to-use and non-invasive biomarker that can be used to monitor patients undergoing surgery for grade 2 and 3 diffuse gliomas, and thus enable earlier diagnosis of recurrence. These biomarkers could be microRNAs. MicroRNAs are small non-coding RNAs involved in the regulation of genes and, consequently, of the intracellular signalling pathways that govern cell behaviour. They are therefore widely implicated in oncogenesis, and in particular in the mechanisms that promote tumour migration, invasion and proliferation. Several preliminary studies have shown that serum levels of pro-oncogenic microRNAs correlate with tumour rates in gliomas. No study has investigated the possibility of using them to detect tumour recurrence earlier in grade 2 and 3 gliomas. With this study, the investigators hope to use pro-oncogenic microRNAs to monitor glioma patients and diagnose early recurrence in grade 2 and 3 gliomas.

Binimetinib in Patients With BRAF Fusion-positive Low-grade Glioma or Pancreatic Cancer (Perfume)

This study is an open-label, parallel, 2-cohort, multicenter, investigator-initiated Phase 2 trial to evaluate the efficacy and safety of binimetinib in patients with advanced or recurrent low-grade glioma or pancreatic cancer harboring BRAF fusion/rearrangement.

Trametinib for Pediatric Neuro-oncology Patients With Refractory Tumor and Activation of the MAPK/ERK Pathway.

This is a phase 2, open-label, interventional clinical trial that will study the response rate of pediatric glioma and plexiform neurofibroma (PN) to oral administration of trametinib. Patients meeting all inclusion criteria for a given study group will receive the study medication at a daily dose of 0.025 mg/kg up to a total of 18 cycles, in 28-day cycles. A total of 150 patients will be recruited as part of this clinical study. Patients aged between 1 month (corrected age) and 25 years old will be eligible, in order to include a maximum of patients affected by low-grade glioma (LGG) and PN. This study includes four groups: patients with neurofibromatosis type 1 (NF1) and LGG, NF1 patients with PN, patients with LGG with a B-Raf Serine/Threonine-protein Kinase/Proto-oncogene Encoding B-Raf (BRAF) fusion and patients with glioma of any grade with activation of the Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinases (MAPK/ERK) pathway. All patients except patients with PN must have failed at least one line of treatment. The study will also explore the molecular mechanisms behind tumor development, progression and resistance to treatment. Furthermore, this study will also explore important aspects for patients with brain tumors by including assessment of quality of life and neuropsychological evaluation.

CEST in Low-grade Glioma Study

Low grade gliomas (LGGs) are malignant, infiltrative and incurable brain tumours that typically present in the younger population. This project proposes to use non-contrast metabolic "Saturation Transfer" (ST)-MRI to evaluate LGG tumour progression and aims to predict early changes in LGG. Early identification of LGG patients whose tumours will progress will permit early interventions. ST-MRI does not involve any intravenous injection of contrast and which acquires metabolic information not seen by standard MRI.

Radiotherapy Versus Radiotherapy Combined With Temozolomide in High-risk Low-grade Gliomas After Surgery

It has been reported that radiation therapy followed by PCV chemotherapy (procarbazine, lomustine and vincristine) could improve progression-free survival (PFS) and overall survival (OS) in patients with high-risk WHO grade 2 gliomas after surgery. However, procarbazine is not available in China. In clinical practice, Chinese doctors often use radiotherapy combined with temozolomide to treat these patients, though large-scale prospective studies are lacking. This trial aims to confirm whether RT combined with temozolomide can improve PFS and OS in patients with high-risk low-grade gliomas.