Study of Cabozantinib With Selumetinib for Plexiform Neurofibromas

Part of paid clinical trials in Birmingham, Alabama.

Sponsor
Girish Dhall, MD
Study ID
NCT06502171
Phase
PHASE1
Status
Not Yet Recruiting

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Conditions

  • Neurofibromatosis 1
  • Plexiform Neurofibroma

Eligibility Criteria

Sex
ALL
Age
16 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Cabozantinib Oral Tablet — DRUG
    Cabozantinib will be taken once a day. It must be swallowed whole and not crushed and taken on an empty stomach. The dose will depend on when a participant enrolls on the study. First group will take 20 mg. If participants are enrolled early in this study, they may receive doses that are lower than those who are enrolled later. Participants will be told what dose they will take when they start the study. Once a dose is started, the dose will not be increased. However, a dose can be reduced up to 2 times if a participant experience adverse events. Cabozantinib may be taken simultaneously with selumetinib.
  • Selumetinib Oral Capsule — DRUG
    Selumetinib will be taken twice a day, at least 6 hours apart. It must be swallowed whole and not crushed and taken on an empty stomach. The dose will depend on when a participant enrolls on the study. First group will take 15 mg twice a day. If participants are enrolled early in this study, they may receive doses that are lower than those who are enrolled later. Participants will be told what dose they will take when they start the study. Once a dose is started, the dose will not be increased. However, a dose can be reduced up to 2 times if a participant experience adverse events.

Study Details

Based on the clinical activity of both selumetinib and cabozantinib as monotherapies in clinical trials, the demonstrated activity of these agents in reduced doses in preclinical studies, and the non-overlapping toxicity profiles, the study will assess the tolerability and efficacy of selumetinib and cabozantinib in combination in participants with NF1 ≥16 years old with progressive and/or symptomatic PN in a phase 1/1b/2 clinical trial. Trial Design Phase 1 This will be an open label, dose escalation phase. Dose level escalation will be determined by a rolling six design. In this design, up to 6 participants can be enrolled at a given dose level and then evaluated for dose limiting toxicity (DLT) within the DLT window. The DLT window is defined as 16 weeks in this study based on the long half-life of cabozantinib and the desire to have maximum confidence about long-term tolerability of the combination prior to proceeding to the next dose level. Phase 1b Once the recommended phase 2 dose has been determined in phase 1, an expanded cohort of 12 participants will be enrolled in phase 1b portion of the study. Phase 2 This will be an open label, single-arm phase using the recommended phase 2 dose.

Key Dates

Start date
Aug 1, 2026
Status verified
Mar 2026
Primary completion
Aug 1, 2033
Completion
Aug 1, 2034

Study Design

Enrollment
30 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Phase 1 cabozantinib and selumetinib combination
    The first enrolled participants will start at dose level one with a starting dose of cabozantinib of 20 mg once daily and a starting dose of selumetinib of 15 mg/m2 twice daily. The doses of drug a participant receives will depend on when the participant enrolls on the study. The first group of participants (3 - 6) will receive selumetinib and cabozantinib at half of the typical dose when given separately. If the side effects are tolerable, the second group of 3 to 6 participants will receive a higher dose of selumetinib and cabozantinib. If the drug combination is well-tolerated, there could be up to 5 groups (maximum 6 participants in each group) with each group taking an increased dose from the previous group's dose. If this is tolerated, then this will be the recommended dose of this combination for the Phase 1b of this study. If the side effects are too severe, the participants will receive a lower dose of both drugs.

Primary Outcome Measure

The number of participants that experienced a dose limiting toxicity when taking cabozantinib and selumetinib together. [ Time Frame: 12 months ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of Alabama at BirminghamBirminghamAlabama34294
Karen Cole-Plourde, BA
[email protected]
2055141317
Juliette Southworth, BS
[email protected]
2055298967
Girish Dhall, MD (PRINCIPAL_INVESTIGATOR)

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By research site
University of Alabama at Birmingham· Birmingham, AL

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