Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults

Completed · Phase 2

Conditions studied: NF1, Neurofibromatosis, Plexiform Neurofibromas

In brief

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.

Key facts

Study ID

NCT02101736

Run by

University of Alabama at Birmingham

People needed

45

Starts

2014-06-01

Expected to finish

2022-02-16

Last updated by the study team

2023-05-24

Who can join

Age: 3 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 <3 cm may be eligible on review.
• Central review or MRI required prior to enrollment.
• Age ≥ 3 years of age at the time of study entry. Subjects ≥ 16 years will be enrolled in Cohort A. Subjects 3 - 15 years will be enrolled in Cohort B.
• Performance Level Karnofsky ≥ 50%. Subjects unable to walk because of paralysis, but up in a wheel chair will be considered ambulatory for purpose of assessing performance score.
• Complete resection of plexiform neurofibroma is not feasible or if subject refuses surgery.
• Fully recovered from acute toxic effects of all prior chemotherapy or radiotherapy.
• No myelosuppressive chemotherapy within 4 weeks of study entry.
• At least 7 days since completion of hematopoietic growth factors.
• At least 14 days since completion of biologic agent.
• At least 4 weeks since receiving any investigational drug.
• Physiologic or stress doses of steroids allowed in patients with endocrine deficiencies.
• At least 6 months from radiation therapy to index tumor and at least 6 weeks from radiation to areas outside of index plexiform neurofibroma.
• At least 3 months from major surgery or at least 1 month from minor surgery. No major surgery anticipated within 3 months of enrollment.
• Adequate bone marrow function.
• Adequate renal function.
• Adequate liver function.
• Blood pressure within upper limit of normal.

You may not qualify if…

• Active optic glioma or other low-grade glioma requiring treatment with chemotherapy or radiation therapy.
• Malignant glioma, malignant peripheral nerve sheath tumor, or other malignancy requiring treatment in the last 12 months.
• Dental braces or prosthesis that interferes with volumetric analysis of the neurofibroma(s).
• Unable to swallow tablets.
• Women who are pregnant or breast-feeding.
• Subjects of reproductive potential who have not agreed to use effective contraception.
• Subject has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs).
• Subject requires anticoagulants. Low dose aspirin, low-dose warfarin, and prophylactic low molecular weight heparin are permitted.
• Concomitant treatment of strong CYP3A4 inducers or inhibitors.
• History of noncompliance to medical regimens
• A known history of HIV seropositivity or known immunodeficiency. HIV testing will not be required as part of this trial, unless HIV is clinically suspected.
• Impairment of gastrointestinal function or gastrointestinal disease that may affect the absorption of cabozantinib. (e.g. ulcerative disease, malabsorption syndrome, or small bowel resection). Nasogastric tube (NG) tube is allowed.
• Any of the following within 28 days before the first dose of study treatment:
• intra-abdominal tumor/metastases invading GI mucosa
• active peptic ulcer disease
• inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
• malabsorption syndrome
• Any of the following within 6 months before the first dose of study treatment:
• abdominal fistula
• gastrointestinal perforation
• bowel obstruction or gastric outlet obstruction
• intra-abdominal abscess. Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating study treatment even if abscess occurred more than 6 months before the first dose of study treatment.
• Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
• Patients who have an uncontrolled infection.
• Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment

Where it is running

• Children's Hospital Los Angeles — Los Angeles, California, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Lurie Children's Hospital of Chicago — Chicago, Illinois, United States
• University of Chicago — Chicago, Illinois, United States
• Indiana Unversity — Indianapolis, Indiana, United States
• National Cancer Institute (NCI) — Bethesda, Maryland, United States
• Children' Hospital Boston and Massachusetts General Hospital — Boston, Massachusetts, United States
• Washington University - St. Louis — St Louis, Missouri, United States
• New York University Medical Center — New York, New York, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.