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Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00704288
Recruitment Status : Completed
First Posted : June 24, 2008
Last Update Posted : July 16, 2014
Sponsor:
Information provided by (Responsible Party):
Exelixis

Tracking Information
First Submitted Date  ICMJE June 20, 2008
First Posted Date  ICMJE June 24, 2008
Last Update Posted Date July 16, 2014
Study Start Date  ICMJE May 2008
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2009)
  • To evaluate the objective response rate for subjects with recurrent or progressive glioblastoma multiforme following treatment with XL184 [ Time Frame: Evaluated approx. every 8 weeks ]
  • Evaluate safety and tolerability of XL184 [ Time Frame: Assessed at all visits ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 20, 2008)
  • To evaluate the 6-month progression-free survival rate of XL184 in subjects with recurrent or progressive glioblastoma multiforme [ Time Frame: Evaluated at approx. 6 months ]
  • Evaluate safety and tolerability of XL184 [ Time Frame: Assessed at periodic visits ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2009)
  • Assess duration of response, 6-month progression-free survival rate,and overall survival [ Time Frame: Assessed during periodically scheduled visits ]
  • Further characterize pharmacokinetics and pharmacodynamic effects of XL184 [ Time Frame: Assessed during periodic visits ]
  • Correlate pathway dysfunction of glioblastoma multiforme-relevant genes such as MET and relevant downstream signaling molecules with clinical outcome [ Time Frame: Assessed during periodic visits ]
  • Correlate changes in serial vascular MRI with clinical outcome and analyze tumor volumetrics based on MRI [ Time Frame: Assessed during periodically scheduled visits, approx. every 8 weeks ]
  • Evaluate the glucocorticoid-sparing effect of XL184 [ Time Frame: Assessed periodically ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2008)
  • Assess response rate, duration of response, and overall survival [ Time Frame: Assessed during periodic visits ]
  • Further characterize pharmacokinetics and pharmacodynamic effects of XL184 [ Time Frame: Assessed during periodic visits ]
  • Correlate pathway dysfunction of glioblastoma multiforme-relevant genes such as MET and relevant downstream signaling molecules with clinical outcome [ Time Frame: Assessed during periodic visits ]
  • Correlate changes in serial vascular MRI with clinical outcome and analyze tumor volumetrics based on MRI [ Time Frame: Assessed during periodic visits ]
  • Evaluate the steroid-sparing effect of XL184 [ Time Frame: Assessed periodically ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme
Official Title  ICMJE A Phase 2 Study of XL184 in Subjects With Progressive or Recurrent Glioblastoma Multiforme in First or Second Relapse
Brief Summary The purpose of this study is to evaluate the objective response rate and 6-month progression-free survival rate of XL184 in subjects with recurrent or progressive glioblastoma multiforme. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma Multiforme
Intervention  ICMJE Drug: XL184
Gelatin capsules supplied in 25-mg and 100-mg strengths; continuous daily dosing
Study Arms  ICMJE Experimental: 1
Intervention: Drug: XL184
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 15, 2014)
222
Original Estimated Enrollment  ICMJE
 (submitted: June 20, 2008)
46
Actual Study Completion Date  ICMJE December 2012
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • The subject has locally determined histologically confirmed diagnosis of Grade 4 astrocytic tumor.
  • The subject has received prior standard radiation for Grade 3 or 4 astrocytic tumor.
  • The subject has received prior temozolomide therapy for Grade 3 or 4 astrocytic tumor (if in first relapse, the subject must have received temozolomide until progression, intolerance, or completion of planned therapy; if in second relapse, the subject must have received temozolomide until progression, intolerance, or completion of planned therapy either for first-line treatment or for treatment after first relapse).
  • The subject is in first or second Grade 4 relapse, defined as having one or two progressions as Grade 4 astrocytic tumor since the original diagnosis of any grade glioma.
  • The subject must have a baseline brain MRI scan within 14 days prior to first dose of XL184 while either not receiving glucocorticoids during the 5 days prior to the baseline MRI scan or on a stable dose of glucocorticoids during the 5 days prior to the baseline MRI scan.
  • Subjects having undergone recent resection or biopsy of tumor will be eligible as long as all of the following conditions apply: First dose of XL184 occurs at least 28 days after surgery, the subject has recovered from the effects of surgery, and the subject has measurable residual disease.
  • The subject is at least 18 years old.
  • The subject has a KPS (Karnofsky Performance Scale) of ≥ 70%.
  • The subject is capable of understanding the protocol 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 3 months following discontinuation of study drug.
  • Female subjects of childbearing potential must have a negative pregnancy test at enrollment.

Exclusion Criteria:

  • The subject has received non-standard radiation therapy for glioblastoma, non-anti-angiogenic therapy (including investigational agents, small-molecule kinase inhibitors, and biologic agents) or non-cytotoxic hormonal agent within 28 days of the first scheduled dose of XL184 or mitomycin C within 42 days of the first scheduled dose of XL184, other investigational therapy (including agents not specified above) within 28 days of the first scheduled dose of XL184, or prior treatment with nitrosoureas (including carmustine wafer) at any time.
  • Some subjects may not have had any prior VEGF- or VEGFR2-based anti-angiogenic therapy (such as bevacizumab, cediranib, or pazopanib).
  • Some subjects may not have had bevacizumab within 14 days of the first scheduled dose of XL184.
  • The subject is receiving warfarin (or other coumarin derivatives) at study entry and unable to switch to low molecular weight heparin.
  • The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study.
  • The subject is unable to undergo MRI scan (eg, has pacemaker).
  • The subject has received enzyme-inducing anti-epileptic agents within 2 weeks before the first dose of XL184 (eg, carbamazepine, phenytoin, phenobarbital, primidone).
  • The subject has not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤ 1 from adverse events (AEs) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered before study enrollment.
  • The subject has evidence of wound dehiscence.
  • The subject is pregnant or breast-feeding.
  • The subject has serious intercurrent illness, such as uncontrolled hypertension, unhealed wounds from recent surgery or cardiac arrhythmias or a recent history of significant disease such as either symptomatic congestive heart failure or unstable angina pectoris within the past 3 months, myocardial infarction within the past 6 months, or active infection requiring systemic treatment/hospitalization within 2 weeks of the first scheduled dose of XL184
  • The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
  • The subject has received any live virus vaccine within 28 days or any inactivated vaccine within 7 days prior to first dose of XL184.
  • The subject has had another diagnosis of malignancy (unless nonmelanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed ≥ 2 years previously) or currently has evidence of malignancy (unless non-melanoma skin cancer or in situ carcinoma of the cervix).
  • The subject has a known allergy or hypersensitivity to any of the components of the XL184 formulations.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00704288
Other Study ID Numbers  ICMJE XL184-201
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Exelixis
Study Sponsor  ICMJE Exelixis
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Exelixis
Verification Date July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP