A Phase II Study of Cabozantinib (XL184) for Plexiform Neurofibromas in Subjects With Neurofibromatosis Type 1 in Children and Adults
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.
• 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.