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

• Register: ClinicalTrials.gov
• Last refreshed on: 23 January 2023
• Main ID: NCT02101736
• Date of registration: 14/03/2014
• Prospective Registration: Yes
• Primary sponsor: University of Alabama at Birmingham
• Public title: Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults NF105-CABO
• Scientific title: A Phase II Study of Cabozantinib (XL184) for Plexiform Neurofibromas in Subjects With Neurofibromatosis Type 1 in Children and Adults
• Date of first enrolment: June 2014
• Target sample size: 45
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02101736
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Chie-Schin Shih, MD
• Affiliation: Indiana University

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Clinical or molecular diagnosis of Neurofibromatosis Type 1

2. Plexiform neurofibroma that is progressive OR causing significant morbidity.

3. 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.

4. Central review or MRI required prior to enrollment.

5. 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.

6. 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.

7. Complete resection of plexiform neurofibroma is not feasible or if subject refuses
surgery.

8. Fully recovered from acute toxic effects of all prior chemotherapy or radiotherapy.

9. No myelosuppressive chemotherapy within 4 weeks of study entry.

10. At least 7 days since completion of hematopoietic growth factors.

11. At least 14 days since completion of biologic agent.

12. At least 4 weeks since receiving any investigational drug.

13. Physiologic or stress doses of steroids allowed in patients with endocrine
deficiencies.

14. At least 6 months from radiation therapy to index tumor and at least 6 weeks from
radiation to areas outside of index plexiform neurofibroma.

15. At least 3 months from major surgery or at least 1 month from minor surgery. No major
surgery anticipated within 3 months of enrollment.

16. Adequate bone marrow function.

17. Adequate renal function.

18. Adequate liver function.

19. Blood pressure within upper limit of normal.

Exclusion Criteria:

1. Active optic glioma or other low-grade glioma requiring treatment with chemotherapy or
radiation therapy.

2. Malignant glioma, malignant peripheral nerve sheath tumor, or other malignancy
requiring treatment in the last 12 months.

3. Dental braces or prosthesis that interferes with volumetric analysis of the
neurofibroma(s).

4. Unable to swallow tablets.

5. Women who are pregnant or breast-feeding.

6. Subjects of reproductive potential who have not agreed to use effective contraception.

7. Subject has not recovered to baseline or CTCAE = Grade 1 from toxicity due to all
prior therapies except alopecia and other non-clinically significant AEs.

8. Subject requires anticoagulants. Low dose aspirin, low-dose warfarin, and prophylactic
low molecular weight heparin are permitted.

9. Concomitant treatment of strong CYP3A4 inducers or inhibitors.

10. History of noncompliance to medical regimens

11. 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.

12. Impairment of gastrointestinal function or gastrointestinal disease that may affect
the absorption of cabozantinib. (e.g. ulcerative disease, malabsorption syndrome, or
small bowel resection). NG tube is allowed.

- Any of the following within 28 days before the first dose of study treatment:

1. intra-abdominal tumor/metastases invading GI mucosa

2. active peptic ulcer disease

3. inflammatory bowel disease (including ulcerative colitis and Crohn's
disease), diverticulitis, cholecystitis, symptomatic cholangitis or
appendicitis

4. malabsorption syndrome

- Any of the following within 6 months before the first dose of study treatment:

1. abdominal fistula

2. gastrointestinal perforation

3. bowel obstruction or gastric outlet obstruction

4. 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 PEG
tube placement within 3 months before the first dose of study therapy

13. Patients who have an uncontrolled infection.

14. Clinically-significant gastrointestinal bleeding within 6 months before the first dose
of study treatment

15. Hemoptysis of =0.5 teaspoon (2.5 mL) of red blood within 3 months before the first
dose of study treatment

16. Any other signs indicative of pulmonary hemorrhage within 3 months before the first
dose of study treatment

17. Radiographic evidence of cavitating pulmonary lesion(s).

18. Concurrent severe and/or uncontrolled medical disease which could compromise
participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension,
severe infection, severe malnutrition, chronic liver or renal disease, active upper GI
tract ulceration)

19. Cardiovascular disorders including:

- Congestive heart failure (CHF): New York Heart Association (NYHA) Class III
(moderate) or Class IV (severe) at the time of screening

- Concurrent uncontrolled hypertension defined as sustained BP > 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 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:

1. unstable angina pectoris

2. clinically-significant cardiac arrhythmias

3. stroke (including TIA, or other ischemic event)

4. myocardial infarction

5. thromboembolic event requiring therapeutic anticoagulation (Note: subjects
with a venous filter (e.g. vena cava filter) are not eligible for this
study)

20. Other clinically significant disorders such as:

- Active infection requiring systematic treatment within 28 days before the first
dose of study treatment

- Serious non-h


Age minimum: 3 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Plexiform Neurofibromas

NF1

Neurofibromatosis

Intervention(s)

Drug: Cabozantinib

Primary Outcome(s)

The change in tumor size based on radiographic assessment [Time Frame: baseline to 12 Months]

Secondary Outcome(s)

The number of subjects experiencing an SAE after receiving cabozantinib [Time Frame: baseline to 24 months]

Secondary ID(s)

IRB-130423015

Source(s) of Monetary Support

Please refer to primary and secondary sponsors