Intermittent Dosing Of Selumetinib In Childhood NF1 Associated Tumours (NCT03326388) | Clinical Trial Compass
CompletedPhase 1/2
Intermittent Dosing Of Selumetinib In Childhood NF1 Associated Tumours
United Kingdom14 participantsStarted 2019-09-26
Plain-language summary
Phase I and II study of the MEK inhibitor Selumetinib given twice daily on 5 out of 7 days in children with NF1 and inoperable plexiform neurofibromas or progressive/relapsed optic pathway gliomas.
This study will test the early and late toxicities of selumetinib when it is given in this intermittent schedule (in 5 out of 7 days) and will also test the effectiveness of the drug in reducing the size of plexiform neurofibromas and optic pathway gliomas in children with NF1. It will also test the effectiveness of the drug in improving the participants function in day to day life.
Who can participate
Age range3 Years ā 18 Years
SexALL
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Inclusion criteria
ā. Age Phase I: ā„3 years and ā¤18 years of age at the time of study enrolment, if able to swallow whole capsules.
ā. Diagnosis: Phase I (Dose escalation): Patients with NF1 and inoperable PNs defined as PNs 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 morbidity or have the potential to cause significant morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, 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.
ā. Measurable disease (PN): Subjects must have at least one measurable PN, defined as a lesion of at least 3 cm measured in one dimension. Subjects who underwent surgery for resection of a PN are eligible provided the PN was incompletely resected and is measurable. Measurable disease (OPG): Subjects must have one measurable OPG lesions according to RANO 1.1 i.e. Tumour ā„10 x10mm in maximal perpendicular dimensions on an axial image on MRI with ā¤5 mm reconstruction interval.
ā. Prior Therapy: Subjects with NF1 will only be eligible if complete tumour resection is not considered to be feasible without substantial risk or morbidity, or if a patient with a surgical option refuses surgery.
ā. Performance status: Patients ā„ 16 years of age must have a Karnofsky performance level of ā„70%, and children \< 16 years old must have a Lansky performance of ā„70% (Error! Reference source not found.). 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.
What they're measuring
1
Phase 1: To evaluate the Maximum Tolerated Dose
Timeframe: 6 months
2
Phase 2: Objective response rate in NF1 inoperable plexiform neurofibroma and optic pathway glioma
Timeframe: 2 years
3
Best Objective response rate in NF1 related optic pathway gliomas
Timeframe: 2 years
Trial details
NCT IDNCT03326388
SponsorGreat Ormond Street Hospital for Children NHS Foundation Trust
ā. Haematological Function: Patients must have an absolute neutrophil count ā„1500/Āµl, haemoglobin ā„9g/dl, and platelet ā„100,000/Āµl.
ā. 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 ā¤ 2.5 x upper limit of normal.
ā. Renal Function: Patients must have a creatinine clearance or radioisotope GFR ā„60ml/min/1.73 m2 or a normal serum creatinine based on age described in the table below.
Exclusion criteria
ā. Pregnant or breast-feeding females are excluded due to potential risks of foetal and teratogenic adverse events of an investigational agent. Pregnancy tests must be obtained prior to enrolment on this study for girls of reproductive potential. The need to commence pregnancy testing will be at the discretion of the treating physician to facilitate taking in to account factors such as precocious puberty, endocrine status and medications which can affect pubertal status. 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.
ā. Known severe hypersensitivity to selumetinib or any excipient of selumetinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib.
ā. Recent major surgery within a minimum of 4 weeks prior to starting study treatment, with the exception of surgical placement for vascular access.
ā. 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 in-evaluable.
ā. An investigational agent within the past 28 days.
ā. Any unresolved chronic toxicity with toxicity ā„ CTCAE Grade 2 from previous anti-cancer therapy, except for alopecia.
ā. Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumour, immunotherapy, or biological therapy.
ā. 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)