Mirdametinib Monotherapy in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF).
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorJohns Hopkins University
About this trial
This is a Phase 1/2a, open-label, non-randomized, multi-dose study of mirdametinib monotherapy in adults with NF1 and cNF.
In both Phases of the study, participation in the study will comprise three periods: screening, treatment and post-study safety follow-up to be performed at the NF1 and cNF specialty center: Johns Hopkins University.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Meet the diagnostic criteria for NF12
≥ 18 years of age
Have a minimum of 24 measurable cNF (2 target areas of ≥6 measurable cNF)
Participants must have cNF that meet eligibility criteria located within the two study designated target areas or outside of the target areas amenable to biopsy. If biopsy is taken within the target area there must be a minimum of 6 cNF remaining for long term surveillance after biopsy. Participants must be willing to undergo pre-, and on-treatment tumor biopsies providing fresh tumor tissue; there should be no contraindication for serial biopsy
Disqualifiers
alanine transaminase (ALT) value of > 2.0 x upper limit of normal (ULN);
total bilirubin value of > 1.5 x ULN (isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%);
Participant has a history of malignancy associated hypercalcemia;
Participant has an active parathyroid disorder, hyperphosphatemia at Screening (serum phosphorus > 1 x ULN), or serum calcium (mg/dL) x serum phosphorus (mg/dL) product > 70 at Screening;
Trial design
Design model
Sequential
Treatments tested in this trial
Mirdametinib
DrugThis study is designed to assess Mirdametinib safety and efficacy in two phases: phase 1 tests the safety of up to four dose regimens of Mirdametinib, administered continuously or intermittently (3 weeks on/1 week off) to identify up to two recommended phase 2 doses. Phase 2a of the study will test the safety and efficacy of the recommended phase 2 dose(s) in adults with NF1 and cNF. The following dosing strategy will be assessed in participants ≥ 18 years old with NF1 and a minimum of 12 measurable cNF who desire systemic treatment of their cNF due to disfigurement, pain or itching. Each treatment cycle in this study is 28 days.treatment cycle in this study is 28 days.
Treatment groups
24 Participants
are divided into 2 treatment groupsGroup A: Phase 1Experimental treatment 1 intervention
Group B: Phase 2Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Assess the safety of continuous and three week on-one week off dosing of mirdametinib in adults with NF1 and cutaneous neurofibromas (cNFs).
Phase 1 will test the safety and tolerability of multiple dose regimens of mirdametinib, in order to identify the recommended phase 2 dose(s) for phase 2a. The study will continue until one of the stopping conditions is met. * The RP2D(s) have been identified with sufficient accuracy (The dose regimen(s) selected as the RP2D have been fully enrolled with at least 3 cycles of treatment completed for all participants) * All dose regimens are deemed to have unacceptable safety The study will continue until one of the following stopping conditions is met. * The RP2D(s) have been identified with sufficient accuracy (The dose regimen(s) selected as the RP2D have been fully enrolled with at least 3 cycles of treatment completed for all participants) * All dose regimens are deemed to have unacceptable safety
Time frame
Up to 28 days2
Define the recommended phase 2 dose (RP2D) of mirdametinib in adults with NF1 and cNF.
Phase 2a of the study will test the efficacy and safety of a maximum of two RP2Ds in adults with NF1 and cNF.
Time frame
Up to 28 days3
• Evaluate the preliminary anti-tumor activity of mirdametinib monotherapy in adults with NF1 and cNFs.
Evaluate the efficacy of mirdametinib monotherapy at the RP2D in adults with NF1 and cNF. We will determine efficacy of Anti-tumor activity with 3D photography (Sum of the surface area, sum of the tumor volume, sum of the longest diameter) and Digital Caliper (Sum of the longest diameter).
Time frame
Up to 28 daysSponsors and contacts
Click on the lead sponsor to view all of their trials.
Johns Hopkins University
Lead sponsor
SpringWorks Therapeutics, Inc.
Collaborator
Source ClinicalTrials.gov