Status and phase
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Study type
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About
To determine the clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic neurofibromatosis type 1 (NF1) associated or sporadic MPNST.
Full description
I. Primary Objective
• To determine the clinical benefit rate of selumetinib in combination with sirolimus in patients with unresectable or metastatic NF1 associated or sporadic MPNST
II. Secondary Objective(s)
Selumetinib will be given orally 50mg twice daily continuously and sirolimus will be given orally 4mg once daily with a cycle 1 day 1 loading dose of 12mg. One cycle will be 28 days. Patients will be able to remain on treatment as long as they do not experience progressive disease or unacceptable toxicity. Stage 1 will require 7 patients, with no further accrual if 0 of 7 respond. If 1 or greater of the 7 patients respond, accrual will continue until 21 patients have been enrolled.
Enrollment
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Volunteers
Inclusion criteria
Exclusion criteria
Patients receiving other anti-cancer agents are not eligible.
Patients who cannot swallow whole pills.
Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent (for example cyclosporine). Topical or inhaled corticosteroids are allowed.
Patients should not receive immunizations with attenuated live vaccines within four weeks of study entry or during study period.
Any recent major surgery within a minimum of 4 weeks, with the exception of surgical placement for vascular access, or minor surgery (excluding tumor biopsies) within 14 days.
Patients who any known severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
Severely impaired lung function defined as spirometry and DLCO that is 50% of the normal predicted value corrected for hemoglobin and alveolar volume and/or O2 saturation that is 88% or less at rest on room air. For patients who do NOT have respiratory symptoms (e.g. dyspnea at rest, known requirement for supplemental oxygen), pulmonary function test is not required.
Cardiac conditions as follows:
Uncontrolled Type 1 or 2 diabetes as defined by fasting serum glucose >1.5 x ULN
Uncontrolled infection
Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome, or renal tubular acidosis.
Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of small bowel, symptomatic inflammatory bowel disease, or ulcerative colitis, or partial or complete bowel obstruction.
Ophthalmological conditions as follows:
Supplementation with vitamin E greater than 100% of the daily recommended dose.
Hypersensitivity to active or inactive excipients of rapamycins (sirolimus, temsirolimus or everolimus) or selumetinib or drugs with similar chemical structures or class to sirolimus or selumetinib.
Patients unwilling or unable to comply with the protocol.
Seville orange, star fruit, grapefruit and their juices, and St. John's Wort use are not allowed while on study.
Exposure to strong or moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) and BCRP if taken within the stated washout periods before the first dose of study treatment.
Exposure to specific substrates of drug transporters OATP1B1, OATP1B3, MATE1 and MATE2K within the appropriate washout periods (a minimum of 5 x reported elimination half-life) before the first dose of study treatment.
Primary purpose
Allocation
Interventional model
Masking
21 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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