Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults (NF105-CABO)
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|ClinicalTrials.gov Identifier: NCT02101736|
Recruitment Status : Active, not recruiting
First Posted : April 2, 2014
Last Update Posted : June 21, 2018
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 NFI 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.
|Condition or disease||Intervention/treatment||Phase|
|NF1 Neurofibromatosis Plexiform Neurofibromas||Drug: Cabozantinib||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Cabozantinib (XL184) for Plexiform Neurofibromas in Subjects With Neurofibromatosis Type 1 in Children and Adults|
|Actual Study Start Date :||June 2014|
|Estimated Primary Completion Date :||May 2021|
|Estimated Study Completion Date :||May 2022|
Experimental: Experimental Agent XL184 (Cabozantinib)
Cohort A (≥ 16 years - closed to accrual): Starting cabozantinib of 40 mg daily by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 60 mg based on dose tolerability. Subjects who do not tolerate 40 mg will dose reduce to 20 mg. Doses will be capped at 60 mg.
Cohort B (3 - 15 years). The starting cabozantinib dose is 30 mg/m2/day by mouth per cycle. Duration of each cycle is 28 days. Subjects will dose escalate after 2 cycles to 40 mg/m2/day based on dose tolerability. Subjects who do not tolerate 30 mg/m2/day will dose reduce to 23 mg/m2/day. Doses will be capped at 60 mg/day max daily dose
Each cohort will enroll up to 24 evaluable subjects with a target minimum of 17 evaluable subjects per cohort.
This is an open label Phase II clinical trial. For both cohorts, subjects will receive cabozantinib orally in continuous cycles. Each cycle is 28 days. In absence of progressive disease or dose limiting toxicity (DLT), subjects may continue therapy for a total of 12 cycles. Subjects with radiographic response (20% or greater reduction in tumor volume) at the end of 12 cycles can continue on therapy for up to an additional year. However, subjects who do not achieve 15% reduction in tumor volume after 8 cycles will be considered treatment failure and taken off study. Subjects will be carefully monitored for toxicities associated with cabozantinib.
- The change in tumor size based on radiographic assessment [ Time Frame: baseline to 12 Months ]We will estimate the objective response rate (ORR) as defined by 20% volumetric MRI response of the target lesion to cabozantinib at 12 months in adolescents and adults with NF1 plexiform neurofibromas by volumetric MRI imaging.
- The number of subjects experiencing an SAE after receiving cabozantinib [ Time Frame: baseline to 24 months ]We will evaluate the toxicity of protracted cabozantinib administration in this patient population by assessing the number of adverse events experienced by subjects.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02101736
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010|
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|United States, Maryland|
|National Cancer Institute (NCI)|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|Children' Hospital Boston and Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02115|
|United States, Missouri|
|Washington University - St. Louis|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|New York University Medical Center|
|New York, New York, United States, 10016|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19096|
|United States, Utah|
|University of Utah|
|Salt Lake City, Utah, United States, 84132|
|Principal Investigator:||Chie-Schin Shih, MD||Indiana University|