Clinical Trials in Spain / NCT05101148
Active, not recruiting
Phase 1
Phase I Study to Assess the Effect of Food on the PK and Gastrointestinal Tolerability of Selumetinib in Adolescent Children With Neurofibromatosis Type 1 Related Plexiform Neurofibromas
NCT05101148 · tracked via the Priya Life Science Spain tracker
Condition(s) studied
Neurofibromatosis Type 1
Investigational drug(s) / intervention(s)
Selumetinib: The dosing regimen for selumetinib (25 mg/m2 bid) will be based on BSA, during T1 and T2 the dose will be 25mg/m2, consistent with the approved prescribing information in the US. If T3 is required, appropriate dose of selumetinib will be defined by Data Review Committee for T3.
Study summary
This study in adolescent participants with NF1 who have inoperable PN is designed to evaluate the effect of a low fat meal on steady state selumetinib exposure; to assess the effect on GI tolerability when selumetinib is dosed under fed and fasted conditions; and potentially, to confirm an appropriate dosing recommendation of selumetinib with a low fat meal that maintains efficacy with acceptable safety. These results may support labelling statements with regard to posology and food.
Eligibility
Inclusion Criteria:
* Male and female participants aged ≥ 12 to \< 18 years at the time of signing the informed consent.
* All study participants must be diagnosed with (i) NF1 per NIH Consensus Development Conference Statement and (ii) inoperable PN. In addition to PN, participants must have at least 1 other diagnostic criterion for NF1 as defined in protocol.
* Participants must require treatment for NF1 and inoperable PN due to actual symptoms or because of the potential to develop significant clinical complications, as judged by the Investigator, as defined in the protocol.
* Participants who have had prior treatment with any MEKi (including selumetinib) may be considered for inclusion in this study.
* Participants must have a BSA ≥ 1.3 and ≤ 2.5 m2
Exclusion Criteria:
* Evidence or suspicion of optic glioma, malignant glioma, MPNST, or other cancer requiring treatment with chemotherapy or radiation therapy
* Prior malignancy requiring active treatment (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the participant had been disease free for ≥ 2 years or which would not have limited survival to \< 2 years).
* A life-threatening illness, medical condition, organ system dysfunction of laboratory finding which, in the Investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of selumetinib, or put the study outcomes at undue risk.
* Participants with clinically significant cardiovascular disease as listed in the protocol.
* Liver function tests: bilirubin \> 1.5 × the ULN for age (with the exception of those with Gilbert syndrome) or AST/ALT \> 2 × upper limit of normal.
* Renal Function: Creatinine clearance or radioisotope glomerular filtration rate \< 30 mL/min/1.73 m2 or a serum creatinine \> 1.2 mg/dL (for participants aged between 12 and 15 years) or \> 1.5 mg/dL for participants aged \> 15 years).
* Participants with abnormal ophthalmological findings/conditions as listed in the protocol.
* Have any unresolved chronic toxicity, associated with previous therapy for NF1-PN: Gastrointestinal toxicity of CTCAE Grade 1 or higher; Have any other unresolved chronic toxicity with CTCAE Grade ≥ 2, except hair changes (such as alopecia or hair lightening).
* Participants who have previously been treated with a MEKi (including selumetinib) and either discontinued treatment or required a dose reduction due to toxicity
* Have had recent major surgery within a minimum of 4 weeks prior to starting study intervention, with the exception of surgical placement for vascular access. Have planned major surgery during the treatment period.
* Any multivitamin containing vitamin E must be stopped at least 7 days prior to initiation of selumetinib.
Primary outcome measure(s)
- Selumetinib area under the plasma concentration-time curve from zero to 12 hours post-dose (AUC0-12) — At pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose (Cycle 1 Day 8 of each treatment period 1, 2 and 3); Each treatment period 1 and 2 has 1 cycle (Each cycle is 28 days). If needed, treatment period 3 will be started approximately 5 cycles later.
To compare the AUC0-12, SS of the fed (same dose and dose adjustment if necessary) versus fasted state - Gastrointestinal Adverse Events graded by CTCAE Ver 5.0 (Grade 1 to 5) — from screening until 30 days after last dose
To investigate the gastrointestinal toxicities of selumetinib capsules after multiple doses - Assessing change of Gastrointestinal toxicity diary: Modified Bristol Stool Form Scale for Children (mBSFS-C) — At screening (at least 14 days), Cycle 1 of each treatment period 1, 2 and 3 (1 cycle is 28 days)
To investigate the gastrointestinal toxicities of selumetinib capsules after multiple doses - Assessing change of Gastrointestinal toxicity diary: Nausea and Vomiting Symptom Rating Scale (adapted from the Children's Cancer and Leukaemia Group) — At screening (at least 14 days), Cycle 1 of each treatment period 1, 2 and 3 (1 cycle is 28 days)
To investigate the gastrointestinal toxicities of selumetinib capsules after multiple doses - Number of patients who take each gastrointestinal medication — From screening until 30 days after last dose
Collecting gastrointestinal concomitant medications taken including, but not restricted to, medications used to treat diarrhoea, nausea and vomiting. - Proportion of patients who take each gastrointestinal medication — From screening until 30 days after last dose
Collecting gastrointestinal concomitant medications taken including, but not restricted to, medications used to treat diarrhoea, nausea and vomiting.
Trial sites (9)
| Facility | City | Region | Status |
|---|---|---|---|
| Research Site | Rochester | Minnesota | |
| Research Site | Akron | Ohio | |
| Research Site | Bydgoszcz | Poland | |
| Research Site | Gdansk | Poland | |
| Research Site | Warsaw | Poland | |
| Research Site | Moscow | Russia | |
| Research Site | Moscow | Russia | |
| Research Site | Barcelona | Spain | |
| Research Site | Madrid | Spain |
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Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT05101148 on ClinicalTrials.gov ↗ ← All trials in Spain