Study of Cabozantinib With Selumetinib for Plexiform Neurofibromas

Summary

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.

Conditions

• Neurofibromatosis 1
• Plexiform Neurofibroma

Interventions

DRUG

Cabozantinib Oral Tablet

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.

DRUG

Selumetinib Oral Capsule

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.

Sponsors & Collaborators

• Children's Hospital of Philadelphia

  collaborator OTHER

• Indiana University

  collaborator OTHER

• United States Department of Defense

  collaborator FED

• Girish Dhall, MD

  lead OTHER

Principal Investigators

• Girish Dhall, MD · University of Alabama at Birmingham

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

16 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-01

Primary Completion

2033-08-01

Completion

2034-08-01

FDA Drug

Yes

Countries

• United States

Study Locations