Phase 2
N=45
Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults
NF1 · Neurofibromatosis · Plexiform Neurofibromas
Bottom Line
View on ClinicalTrials.gov: NCT02101736 ↗Enrolled (actual)
45
Serious AEs
15.6%
Results posted
May 2023
Primary outcome: Primary: The Change in Tumor Size Based on Radiographic Assessment — -15.7; -4.1 mm^3
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cabozantinib (Drug)
- Age
- Pediatric, Adult, Older Adult · 3+ yrs
- Sex
- All
- Sponsor
- University of Alabama at Birmingham
- Primary completion
- Feb 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Change in Tumor Size Based on Radiographic Assessment |
-15.7; -4.1 | — |
| SECONDARY Number of Participants With Adverse Events |
20; 21 | — |
Summary
This study, "A Phase II Study of Cabozantinib (XL l84) for Plexiform Neurofibromas in Subjects with Neurofibromatosis Type I in Children and Adults diagnosed with Neurofibromatosis Type 1 (NF1) and have a type of tumor called a plexiform neurofibroma (PN). Neurofibromas are tumors that develop from the cells and tissues that cover the nerves. Plexiform neurofibromas can be disfiguring, painful, and life-threatening. These types of tumors typically do not respond well to most treatment approaches such as chemotherapy, radiation, and surgery because of their slow growth and location near vital structures of the body such as nerves, blood vessels, and the airway.
The primary objective is to determine the response rate of NF1 patients with plexiform neurofibromas treated with Cabozantinib therapy using MRI scans. The objective response rate to cabozantinib is defined as ≥ 20% reduction in tumor volume at the end of 12 cycles.
Eligibility Criteria
Inclusion Criteria
- Clinical or molecular diagnosis of Neurofibromatosis Type 1
- Plexiform neurofibroma that is progressive OR causing significant morbidity.
- Measurable disease amenable to volumetric MRI imaging defined as lesion seen on at least 3 consecutive MRI slices and at least 3 mL in volume. Select tumors 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days before the first dose of study treatment
- Any history of congenital long QT syndrome
- Baseline heart-rate corrected QT (QTc) interval >470 msec in women and >450 msec in men
- Concomitant treatment with medications that prolong the QT interval and have a known risk of Torsades de Pointes is not contraindicated, but should be avoided if possible and will require more frequent EKG monitoring.
- Any of the following within 6 months before the first dose of study treatment:
- unstable angina pectoris
- clinically-significant cardiac arrhythmias
- stroke (including transient ischemic attack (TIA), or other ischemic event)
- myocardial infarction
- thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study)
- Other clinically significant disorders such as:
- Active infection requiring systematic treatment within 28 days before the first dose of study treatment
- Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
- History of organ transplant
- Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
- Complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of study treatment irrespective of time from surgery.
Data sourced from ClinicalTrials.gov (NCT02101736). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.