Clinical Research Directory

Tovorafenib for Treatment of Craniopharyngioma in Children and Young Adults

The current study assesses the tolerability and efficacy of monotherapy with pan-RAF-kinase (Tovorafenib) inhibition for the treatment of children and young adults with craniopharyngioma.

Food Preferences and Craniopharyngiomas

The hypothalamus plays a key role in regulating appetite, satiety, and energy balance. When tumors such as craniopharyngiomas develop in this region, they can disrupt these mechanisms and lead to a form of severe weight gain known as hypothalamic obesity. Several factors play a role in the development of hypothalamic obesity that is often resistant to traditional treatments. Changes in food preferences notably a higher liking for food rich in fat and sugar may be implicated as has been reported in common obesity. The working hypothesis of the study is that hypothalamic lesions may alter food preferences, leading to an increased preference for high-fat and high-sugar foods, and that these changes in dietary choices contribute among other factors to the development of hypothalamic obesity. By providing the first evaluation of food preferences in adults treated surgically for craniopharyngiomas, this study will shed light on the role of hypothalamic lesions in modifying dietary choices. The results may help explain why some patients experience rapid and resistant weight gain, and could guide future strategies to better manage hypothalamic obesity.

Methionine PET/CT Studies In Patients With Cancer

The purpose of this study is to test the usefulness of imaging with radiolabeled methionine in the evaluation of children and young adults with tumor(s). Methionine is a naturally occurring essential amino acid. It is crucial for the formation of proteins. When labeled with carbon-11 (C-11), a radioactive isotope of the naturally occurring carbon-12, the distribution of methionine can be determined noninvasively using a PET (positron emission tomography) camera. C-11 methionine (MET) has been shown valuable in the monitoring of a large number of neoplasms. Since C-11 has a short half life (20 minutes), MET must be produced in a facility very close to its intended use. Thus, it is not widely available and is produced only at select institutions with access to a cyclotron and PET chemistry facility. With the new availability of short lived tracers produced by its PET chemistry unit, St. Jude Children's Research Hospital (St. Jude) is one of only a few facilities with the capabilities and interests to evaluate the utility of PET scanning in the detection of tumors, evaluation of response to therapy, and distinction of residual tumor from scar tissue in patients who have completed therapy. The investigators propose to examine the biodistribution of MET in patients with malignant solid neoplasms, with emphasis on central nervous system (CNS) tumors and sarcomas. This project introduces a new diagnostic test for the noninvasive evaluation of neoplasms in pediatric oncology. Although not the primary purpose of this proposal, the investigators anticipate that MET studies will provide useful clinical information for the management of patients with malignant neoplasms.

Clinical Trial of an Anti-Fog Drainage Device for Endoscopic Endonasal Sellar Region Tumor Surgery

The goal of this clinical trial is to learn if the anti-fog suction device works to keep the surgical view clear during endoscopic nose-to-pituitary operations and whether it lowers the chance of brain-fluid infection. It will also learn about the safety of the device. The main questions it aims to answer are: * Does the device reduce the total time the surgeon has to stop because the lens fogs up? * What medical problems (such as nose-bleed, tube blockage, or infection) do participants have when the device is used? Researchers will compare the anti-fog device to the usual "water-squirt" method to see if the device works better. Participants will: * Have either the device or the usual water method applied during their planned pituitary surgery * Stay in the hospital for the normal recovery period (about 3-5 days) and return for a routine check-up around day 7 * Allow the study team to record operating times, any fog-related pauses, and results of blood or spinal-fluid tests taken before and after surgery

A Phase II Trial of Intensity-Modulated Proton Therapy for Incompletely Resected Craniopharyngioma and Observation for Craniopharyngioma After Radical Resection

Craniopharyngioma is a rare brain tumor that affects both children and adults. It arises in a region of the brain near the pituitary gland, visual pathways, and central blood vessels. Patients often present with headache, loss of vision or delayed growth. In some instances they may present with imbalance of water and salts in the body. The treatment for craniopharyngioma may be radical surgery or a combination of surgery and radiation therapy. In some instances surgery is not required. If the tumor cannot be completely removed, radiation therapy may be required. In this study we will use the most advanced form of proton therapy which is called intensity-modulated proton therapy. This is a newer form of radiation therapy which has a number of advantages over older forms of proton therapy and conventional radiation therapy using x-rays. The main goal of this study is to learn if proton therapy will effectively treat patients with craniopharyngioma brain tumors and reduce side effects compared to more traditional forms of radiation therapy.

A Phase II Trial of Limited Surgery and Proton Therapy for Craniopharyngioma or Observation After Radical Resection

The goal of this study is to determine the feasibility and safety of treating patients with a brain tumor known as craniopharyngioma with limited surgery and a 5mm clinical target volume margin in combination with proton therapy. Proton therapy will be indicated for patients with diagnosed craniopharyngioma who are not treated with radical surgery (gross-total resection). Irradiated patients will undergo a series of evaluations designed to evaluate the effects of proton therapy. Similar evaluations will be performed on patients treated with radical surgery. Proton therapy will include 30 treatment fractions administered 5 days per week. Weekly imaging will be a requirement to monitor for cyst expansion and target volume deformation.

ImmunoPET Targeting Trophoblast Cell-surface Antigen 2 (Trop-2) in Craniopharyngioma Patients

This study aims to investigate 68Ga-MY6349, an immune-PET tracer targeting trophoblast cell surface antigen 2 (Trop2), for the noninvasive diagnosis of craniopharyngioma in vivo.

Efficacy and Safety of Phentermine/Topiramate in Youth With Hypothalamic Obesity

Hypothalamic obesity (HO) refers to the substantial weight gain that often complicates hypothalamic brain tumors. Children with this treatment-recalcitrant form of obesity have excess rates of metabolic sequelae compared to otherwise healthy children with similar obesity, and later experience excess mortality related to cardiometabolic disease. In this pilot trial, our objective is to gather key preliminary data about phentermine/topiramate (Ph/T) that is FDA-approved for "common" obesity but has never been tested in HO. The subset of individuals with HO who experience hyperphagia or excess daytime sleepiness may benefit from the Ph/T-induced decrease in appetite and increase in alertness. Preliminary assessments of safety, adverse events, dosing (Aim 1), as well as of efficacy (% BMI loss, Aim 2) will be made in a 28-week parallel-arm double-blinded Phase 2 placebo-controlled clinical trial in 6-28-year-old individuals with HO.

Long-Term Longitudinal QoL in Patients Undergoing EEA

This is a prospective longitudinal study to access postoperative 2-year quality of life in patients who undergo endonasal endoscopic approach surgeries of the skull base.

The Impact of Endoscopic Endonasal Skull Base Surgery on Olfaction

In this study, the research team will investigate the incidence and etiology of olfactory dysfunction following endoscopic endonasal skull base surgery, by combining clinical assessments with histomolecular analysis.

Craniopharyngioma and Pregnancies

Craniopharyngiomas (CP) are rare hypothalamic-pituitary tumors found in young children, adolescents and adults. The management of PC remains complex, as their aggressive nature, invasive behavior and propensity to recur require sequential and balanced therapeutic attitudes, as well as follow-up in an expert center. Although patient survival rates are high, the consequences of the tumor and its treatment can lead to serious comorbidities and impaired quality of life, particularly in patients whose tumors extend to the hypothalamus. There is very little literature describing the outcome of pregnancy in craniopharyngioma patients and its impact on the craniopharyngioma. The largest study describes 6 women, mean age 24, who had a craniopharyngioma in childhood. Half of them had induced pregnancies; there is a succinct description of pregnancy complications and outcomes, as well as tumor progression. In the endocrinology department of Pitié Salpêtrière hospital, the investigators regularly follow over a hundred patients of all ages who have presented with a craniopharyngioma in childhood or adulthood. They are also unique in having a medically assisted reproduction unit, which helps couples to realize their parental project. This dual specialization will enable to describe pregnancies and their impact on the behavior of craniopharyngiomas.

Proton Therapy Research Infrastructure- ProTRAIT- Neuro-oncology

The first proton therapy treatments in the Netherlands have taken place in 2018. Due to the physical properties of protons, proton therapy has tremendous potential to reduce the radiation dose to the healthy, tumour-surrounding tissues. In turn, this leads to less radiation-induced complications, and a decrease in the formation of secondary tumours. The Netherlands has spearheaded the development of the model-based approach (MBA) for the selection of patients for proton therapy when applied to prevent radiation-induced complications. In MBA, a pre-treatment in-silico planning study is done, comparing proton and photon treatment plans in each individual patient, to determine (1) whether there is a significant difference in dose in the relevant organs at risk (ΔDose), and (2) whether this dose difference translates into an expected clinical benefit in terms of NormalTissue Complication Probabilities (ΔNTCP). To translate ΔDose into ΔNTCP, NTCP-models are used, which are prediction models describing the relation between dose parameters and the likelihood of radiation-induced complications. The Dutch Society for Radiotherapy and Oncology (NVRO) setup the selection criteria for proton therapy in 2015, taking into account toxicity and NTCP. However, NTCP-models can be affected by changes in the irradiation technique. Therefore, it is paramount to continuously update and validate these NTCP-models in subsequent patient cohorts treated with new techniques. In ProTRAIT, a Findable, Accessible, Interoperable and Reusable (FAIR)data infrastructure for both clinical and 3D image and 3D dose information has been developed and deployed for proton therapy in the Netherlands. It allows for a prospective, standardized, multi-centric data from all Dutch proton and a representative group of photon therapy patients.

Treatment of BRAF ( B-Rapidly Accelerated Fibrosarcoma) Mutated Papillary Craniopharyngioma

Subjects with papillary craniopharyngioma harboring a BRAF mutation will be treated with a BRAF + MEK inhibitor (dabrafenib + trametinib) after informed consent. Study participants will be administered oral dabrafenib and trametinib until maximal tumor volume reduction assessed by MRI. Progression free survival, cognition, ophthalmologic status, hypothalamic status and quality of life will be assessed 1 year after initiation of study treatment