Clinical Research Directory

Phase I Trial of TURALIO(R) (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor ...

Background: \- Some people with cancer have solid tumors. Others have refractory leukemia. This may not go away after treatment. Researchers want to see if a drug called TURALIO(R) can shrink tumors or stop them from growing. Objectives: \- To find the highest safe dose and side effects of TURALIO(R). To see if it helps treat certain types of cancer. Eligibility: \- People ages 3-35 with a solid tumor or leukemia that has returned or not responded to cancer therapies. Design: * Individuals will be screened with: * Medical history * Physical exam * Blood and urine tests * Heart tests * Scans or other tests of the tumor * Individuals will take TURALIO(R) as a capsule once daily for a 28-day cycle. They can do this for up to 2 years. * During the study, participants will have many tests and procedures. They include repeats of the screening tests. Individuals will keep a diary of symptoms. * Individuals with solid tumors will have scans or x-rays. * Individuals with leukemia will have blood tests. They may have a bone marrow sample taken. * Some individuals may have a biopsy. * When finished taking TURALIO(R), individuals will have follow-up visits. They will repeat the screening tests and note side effects.

AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors

Background: \- Plexiform neurofibromas are tumors that grow in and around nerves. The only way to treat them is with surgery. Some of these tumors cannot be completely removed. The tumors may be too large, too numerous, or in a bad location for surgery. An experimental drug called AZD6244 hydrogen sulfate may be able to prevent the tumors from growing, slow down their growth, or shrink them. This drug has been tested in adults with cancer and in children with some types of brain cancer. This study will test how well this drug works with these types of tumors. Objectives: \- To study the safety and effectiveness of AZD6244 hydrogen sulfate in children and young adults with plexiform neurofibromas that cannot be completely removed by surgery. Eligibility: \- Children and young adults between 12 and 18 years of age who have plexiform neurofibromas that cannot be completely removed by surgery. Design: * Patients will be screened with a physical exam, medical history, blood tests, and imaging studies. * They will take the study drug twice a day with 8 ounces of water, every day for 28-day cycles of treatment. During study visits, participants will have blood and urine tests and physical exams. They will also have imaging studies to examine the tumor sizes and locations. They will answer questions about their health. They may have other tests as needed. * Participants will continue to receive the study drug as long as they have no severe side effects and the disease is not getting worse.

Real-World Treatment Study of Koselugo (Selumetinib)

As part of a post-approval commitment, the Korean health authority requests a study to characterize safety and effectiveness in patients treated with Koselugo (Selumetinib), an oral selective inhibitor of MAPK kinase (MEK) 1 and 2, by physicians in routine clinical practice settings. This study is designed to assess the known safety profile or identify previously unsuspected adverse reactions and evaluate the effectiveness of Koselugo under conditions of routine daily medical practice in Korea. This study will provide information on the Korean patient population that is treated with the study drug.

Observational Study to Evaluate the Effect and Safety of Selumetinib in Pediatric Patients With NF1-PNs

This is a prospective, multicenter, observational study of Chinese pediatric NF1-PN patients treated with selumetinib. The study will be conducted at approximately 12 centers in China and will include approximately 80-100 patients. Treatment centers that have PN diagnosis and/or selumetinib treatment experience will be targeted for recruitment. Patients/caregivers who are eligible and willing to participate will be enrolled into the study. Patients will start selumetinib treatment after enrollment. The study will have a 16-month enrollment period. Patients will be followed up until the end of a 24-month observation period after first dose of selumetinib, or patient death, lost to follow-up, withdrawal of consent, whichever occurs first. Patients will be followed within a 24-month period (starting after first dose received) in the study even if selumetinib is discontinued. The aims of this study are to expand understanding of disease characteristics and treatment pattern of NF1-PN in China in a real-world setting and to evaluate real-world effectiveness and safety of selumetinib for Chinese pediatric patients with NF1-PN

PAS-004 in Adults Who Have Neurofibromatosis Type 1 With Plexiform Neurofibromas

The main purpose of this clinical trial is to test PAS-004 in people with at least one symptomatic plexiform neurofibroma due to Neurofibromatosis Type 1 (NF1). The main questions it aims to answer are: * How well participants are able tolerate different doses of PAS-004, and * What side effects PAS-004 might have. This study will have two parts, Part A and Part B. The main goal of Part A of this study is to learn more about how participants tolerate different doses of PAS-004, and what side effects PAS-004 might have. What we learn from Part A of the study will help decide what doses of the study drug (PAS-004) should be used in Part B of the study, and if it is safe. In Part B, two different doses from Part A will be tested. The main goal of this part of the study is to keep studying any side effects of PAS-004 at those two dose levels, and to learn more about if the doses picked for this part of the study might have an effect on plexiform neurofibromas. Participants in Part A of the study who were taking doses selected for Part B may be able to continue on to Part B and keep taking the same dose of PAS-004 for 6 more months. Study participants in both parts will have regular visits to the study doctor and be asked to have tests and exams done to check on their health and safety, including blood draws and MRIs. Everyone participating in the study will take PAS-004 by mouth once a day during the study, in 28-day cycles. Participants will be asked to keep a diary to record their daily dose of study drug. Participants will continue on daily PAS-004 for up to 6 months, or until: * They decide to withdraw from the study, or * They experience unacceptable side effects, or * Their disease progresses, or another illness interferes with taking the study drug, or * The sponsor selects a dose level to study further in the next part of the study, or * The sponsor stops the study.

Treatment of NF1-related Plexiform Neurofibroma With Trametinib

This trial, Treatment of NF1-related plexiform neurofibroma with trametinib; a single arm,open-label study with the goals of volumetric partial remission and pain relief (EudraCT 2018-001846-32, Sponsor protocol number BUS2018-1, related Novartis reference number CTMT212ASE01T) is a pediatric clinical trial that investigates the potential use of the drug trametinib (Mekinist®) as treatment for symptomatic or likely to become symptomatic NF1-related plexiform neurofibromas (PN) in children between 1 year and 17 year and 11 months of age. Trametinib is orally administered qd at 0.025 mg/kg up to a maximum of 2 mg from six years of age and 0.032mg/kilo up to 5 years of age, provided either as tablets or as oral solution. It is manufactured and distributed by Novartis under the trade name Mekinist®. The primary endpoint is remission of tumor volume ≥20%, evaluated using volumetric MRI at 18 and 30 months of treatment. The secondary endpoint is reversal of pain from NF1-related PN, evaluated monthly with agespecific pain scales; VAS scale (from 8 years) or Faces Pain Scale (from 3 to 8 years). As an exploratory measure, the potential effects of the treatment on the cognitive function will be assessed using well-established tests such as WISC-V (age range 6:0 - 16:11), NEPSY-II (age range 3:0-16:11), and CPT-3 (age range 8:0 - adult). Cognitive dysfunction is well described in patients with NF1, and the MAPK/ERK-pathway has been indicated to be involved in cognition.

Evaluation of Percutaneous Cryotherapy in the Treatment of Plexiform Neurofibromas and Unresectable Neurofibromas in Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease affecting chromosome 17. It is manifested by a neurogenic tumor proliferation that forms cutaneous, subcutaneous or deep neurofibromas. Neurofibromas can cause functional discomfort, neurogenic pain that is difficult to treat, and severe cosmetic disorders. Treatment is essentially surgical. It is sometimes a heavy invasive surgery with complicated postoperative follow-up and significant scarring on the aesthetic level. Currently, no systemic treatment has proven its effectiveness in this pathology. Percutaneous cryotherapy is a cold thermoablation procedure using fine 17 G needles introduced into the lesion after targeting by imaging. This technique is used in the treatment of soft tissue tumors and desmoid tumors. The treatment of neurofibromas with percutaneous cryotherapy is not well known. Encouraging results (unpublished) have been observed in patients with NF1 treated with cryotherapy at the Léon Bérard Center. The beneficial effect was observed in terms of quality of life (in particular, pain) as well as a decrease in tumor size. On the basis of this first experience, it appears important to corroborate these preliminary results by a prospective study allowing the use of this technique to treat patients with unresectable or resectable neurofibromas but with mutilating surgery in a NF1 context.