AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors (NCT01362803) | Clinical Trial Compass
Active — Not RecruitingPhase 1/2
AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors
United States99 participantsStarted 2011-09-21
Plain-language summary
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.
Who can participate
Age range2 Years – 18 Years
SexALL
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Inclusion criteria
✓. Age Phase I: \>=3 years and \<=18 years of age at the time of study enrollment, if able to swallow whole capsules. The age limits including young children were chosen because early childhood and puberty are considered to be the greatest risk for disease progression, and selumetinib may provide the most benefit to this young group of patients. In addition, an important objective of this study is to characterize the pharmacokinetics of selumetinib in the pediatric population since it has been well studied in adults.
✓. Diagnosis: Patients with NF1 and inoperable PN, defined as PN that cannot be surgically completely removed without risk for substantial morbidity due to encasement of, or close proximity to, vital structures, invasiveness, or high vascularity of the PN. The PN has to cause (stratum 1) or have the potential to cause (stratum 2) significant morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, paraspinal lesions that can cause myelopathy brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions. Patients will be enrolled into stratum 1 or 2 based on PN related morbidity.
✓. Measurable disease: Patients must have at least one measurable PN, defined as a lesion of at least 3 cm measured in one dimension. Patients who underwent surgery for resection of a PN are eligible provided the PN was incompletely resected and is measurable.
✓. Prior Therapy: Patients with NF1 will only be eligible if complete tumor resection is not considered to be feasible without substantial risk or morbidity.
What they're measuring
1
Ph2: Evaluate the confirmed partial and complete response rate of selumetinib in children and young adults with NF1 and inoperable PN.
Timeframe: prior to cycles 5,6,13,17,21,25 and then every 6 cycles
✓. Performance status: Patients \>= 16 years of age must have a Karnofsky performance level of \>=70%, and children \<= 16 years old must have a Lansky performance of \>=70%. Patients who are wheelchair bound because of paralysis secondary to a plexiform neurofibroma should be considered ambulatory when they are up in their wheelchair. Similarly, patients with limited mobility secondary to need for mechanical support (such as an airway PN requiring tracheostomy or CPAP) will also be considered ambulatory for the purpose of the study.
✓. Hematologic Function: Patients must have an absolute neutrophil count \>=1500/microliter, hemoglobin \>=9g/dl, and platelets \>=100,000/microliter.
✓. Hepatic Function: Patients must have bilirubin within 1.5 x the upper limit of normal for age, with the exception of those with Gilbert syndrome, and AST/ALT within \<= 3 x upper limit of normal.
✓. Renal Function: Patients must have a creatinine clearance or radioisotope GFR \>=60ml/min/1.73 m\^2 or a normal serum creatinine based on age, described below.
Exclusion criteria
✕. Pregnant or breast-feeding females are excluded due to potential risks of fetal and teratogenic adverse events of an investigational agent. Pregnancy tests must be obtained prior to enrollment for all females of childbearing potential as per institutional standards (at NIH subjects 9 years and older or those showing pubertal development). Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Abstinence is an acceptable method of birth control.
✕. Phase I: Patients who anticipate the need for surgical intervention within the first three cycles (3 months), as surgical intervention during the period of DLT evaluation may affect analysis of adherence and/or make the subject inevaluable.
✕. Use of an investigational agent within the past 30 days.
✕. Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor, immunotherapy, or biologic therapy.
✕. Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses, or renal transplant, including any patient known to have hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) will be excluded. Patients with HIV who have adequate CD4 count, not requiring antiretroviral medication, may be enrolled.
✕. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
✕. Inability to swallow capsules, since capsules cannot be crushed or broken.
✕. Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol. Prosthesis or orthopedic or dental braces that would interfere with volumetric analysis of target PN on MRI.