Multiple Doses and Regimens of Cabozantinib in Subjects With Grade IV Astrocytic Tumors in First or Second Relapse

A Phase 2 Non-Comparative Randomized Open-Label Study of Multiple Regimens of Single-Agent XL184 in Subjects With Grade IV Astrocytic Tumors in First or Second Relapse

This study was conducted in subjects with grade IV astrocytic tumors (a type of cancer that can occur in the brain or spinal cord) in first or second relapse.

Study Overview

• Status: Terminated
• Conditions: Astrocytic Tumors
• Intervention / Treatment: Drug: Cabozantinib

Detailed Description

The goal of this clinical trial is to learn if the drug cabozantinib works for people with astrocytic tumors. It also was designed to learn about the safety of cabozantinib. The main questions are:

1. Does cabozantinib work and how well do patients tolerate the drug for over 12 weeks.
2. Was the drug safe and how well could patients tolerate treatment for the entire treatment period.

Participants were assigned to one of the four treatment groups:

Arm 1. Take cabozantinib at a dose of 25 mg once every day (po QD) continuously until progression.

Arm 2. Take cabozantinib at a dose of 75 mg once every day continuously until progression.

Arm 3. Take cabozantinib at a dose of 125 mg once every day for 2 weeks, followed by 50 mg every day (po QD) for the remainder of the treatment period;

Arm 4. Take cabozantinib at a dose of 125 mg once every day for 2 weeks, followed by 1 week off. For the remainder of the treatment period, patients received cabozantinib at a dose of 125 mg once every day for three weeks followed by one week of rest.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
  • Quebec
    • Montreal, Quebec, Canada
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
  • California
    • Encinitas, California, United States, 92024
    • Pleasant Hill, California, United States, 94523
  • Illinois
    • Chicago, Illinois, United States, 60637
    • Chicago, Illinois, United States, 60611
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
  • Michigan
    • Detroit, Michigan, United States, 48202
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
  • New York
    • Amherst, New York, United States, 14226
    • Rochester, New York, United States, 14642
  • Ohio
    • Cleveland, Ohio, United States, 44195
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
  • Texas
    • Dallas, Texas, United States, 75246
    • Dallas, Texas, United States, 75426
    • San Antonio, Texas, United States, 78229
  • Virginia
    • Charlottesville, Virginia, United States, 22908
  • Washington
    • Seattle, Washington, United States, 98122

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The subject has histologically confirmed diagnosis at any time of grade IV astrocytic tumor as determined by the investigator. Tumor samples will be required for pathology review.
• The subject has received prior standard radiation for any grade astrocytic tumor.
• The subject has received prior temozolomide (Temodar) therapy
• The subject has had one or two progressions as grade IV astrocytic tumor from any grade, as determined by investigator
• The subject must have a qualifying brain MRI scan within a specific timeframe prior to start of study treatment
• For subjects with recent tumor resection or biopsy, starting on study must occur a specified amount of time after the surgery and the subject must have recovered from the effects of surgery
• The subject has a Karnofsky Performance Status ≥ 70% and has the ability to swallow whole capsules
• The subject is capable of understanding the informed consent and has signed the informed consent document
• The subject has adequate organ and marrow function
• Sexually active subjects (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 6 months following discontinuation of study treatment
• The subject has had no other diagnosis of malignancy (certain exceptions apply)
• Female subjects of childbearing potential must have a negative pregnancy test at screening

Exclusion Criteria:

• The subject has received certain prior anticancer therapies within a certain amount of time before starting study treatment
• The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin
• The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or CT scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible
• The subject is unable to undergo MRI scan (eg, has pacemaker)
• The subject has received enzyme-inducing anti-epileptic agents within a certain time prior to starting study treatment (eg, carbamazepine, phenytoin, phenobarbital, primidone)
• The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤ 1 from AEs (except alopecia and lymphopenia) due to surgery, or other medications that were administered prior to study start
• The subject has evidence of unhealed wounds
• The subject is pregnant or breast-feeding
• The subject has serious intercurrent illness or a recent history of serious disease
• The subject has inherited bleeding diathesis or coagulopathy (disease affecting how blood clots) with the risk of bleeding
• The subject has a history of any medical or surgical conditions (eg, stomach or intestinal surgery or resection) that would potentially interfere with or alter gastrointestinal function
• The subject has a history of idiopathic pulmonary fibrosis or interstitial lung disease
• The subject has received any live virus vaccine or any inactivated vaccine within a certain amount of time before starting study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - cabozantinib, 25 mg; Starting dose of 25 mg, once a day by mouth (po QD) continuously	Drug: Cabozantinib; Other Names: XL-184
Experimental: Arm 2 - cabozantinib, 75 mg; Starting dose of 75 mg, po QD, continuously	Drug: Cabozantinib; Other Names: XL-184
Experimental: Arm 3 - cabozantinib, 125 mg followed by 50 mg; Starting dose of 125 mg, po QD for 2 weeks, followed by 50 mg, po QD for the remainder of the treatment period.	Drug: Cabozantinib; Other Names: XL-184
Experimental: Arm 4 - cabozantinib, 125 mg; Initially, the starting dose was 125 mg, po QD for 2 weeks, followed by 1 week off. For the remainder of the treatment, the dosing frequency was reduced to 125 mg, po QD every 3 weeks, followed by 1 week of rest for the remainder of the treatment period.	Drug: Cabozantinib; Other Names: XL-184

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Randomized Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An AE was defined as any event with an onset date on or after the date of first dose of study drug, or any ongoing event on the date of first dose that worsened in severity after the date of first dose. TEAEs were defined as AEs that started on or after the first administration of study drug up to the date of last dose plus 30 days. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.	Up to 13 months
Expansion Phase: Objective Response Rate (ORR)	ORR was defined as the number of participants for whom the best overall response at the time of data cutoff is confirmed complete response (CR) or confirmed partial response (PR) as assessed per modified Response Assessment in Neuro-Oncology (RANO) criteria. CR = Disappearance of all enhancing target lesion(s) and no glucocorticoids (other than a physiologic replacement dose of a maximum of 1.2 mg dexamethasone equivalent dose per day) taken for the 5 days immediately preceding the date of the current magnetic resonance imaging (MRI). PR = ≥50% decrease in the sum of the products of perpendicular diameters of all target enhancing lesions on the current MRI scan compared to the baseline MRI scan and glucocorticoids stable or decreased. The sponsor terminated the study early due to business reasons before entering the expansion phase. As such, no data were collected for efficacy analyses.	Up to 13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expansion Phase: Progression Free Survival at 6 Months as Per Independent Radiology Facility	Progression-free survival at 6 months (PFS6) was defined as the proportion of participants alive and progression-free 182 days after Study Day 1. The sponsor terminated the study early due to business reasons before entering the expansion phase. As such, no data were collected for efficacy analyses.	Month 6

Collaborators and Investigators

• Sponsor: Exelixis

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: February 12, 2010
• First Submitted That Met QC Criteria: February 12, 2010
• First Posted (Estimated): February 15, 2010

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Glioma; Brain Tumor; Glioblastoma; Brain Cancer; Astrocytoma
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Glioblastoma; Glioma; Brain Neoplasms; Astrocytoma; cabozantinib
• Other Study ID Numbers: XL184-205