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Study of XL184 in Adults With Glioblastoma Multiforme
This study is currently recruiting participants.
Verified by Exelixis, June 2009
First Received: June 20, 2008   Last Updated: June 23, 2009   History of Changes
Sponsored by: Exelixis
Information provided by: Exelixis
ClinicalTrials.gov Identifier: NCT00704288
  Purpose

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.


Condition Intervention Phase
Glioblastoma Multiforme
Drug: XL184
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase 2 Study of XL184 in Subjects With Progressive or Recurrent Glioblastoma Multiforme in First or Second Relapse

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Evaluate safety and tolerability of XL184 [ Time Frame: Assessed at all visits ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess duration of response, 6-month progression-free survival rate,and overall survival [ Time Frame: Assessed during periodically scheduled visits ] [ Designated as safety issue: No ]
  • Further characterize pharmacokinetics and pharmacodynamic effects of XL184 [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Evaluate the glucocorticoid-sparing effect of XL184 [ Time Frame: Assessed periodically ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: May 2008
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental Drug: XL184
Gelatin capsules supplied in 25-mg and 100-mg strengths; continuous daily dosing

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject has radiographic evidence of progressive or recurrent GBM by MRI scan (performed within the past 14 days and while on a fixed or decreasing dose of glucocorticoids for at least 5 days), and in first or second relapse.
  • Subjects having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: At least 2 weeks since surgery and the subject has recovered from the effects of surgery (residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a baseline MRI should be done within 14 days before the first dose of XL184. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required on a stable or decreasing steroid dose for at least 5 days).
  • The subject is at least 18 years old.
  • The subject has a KPS (Karnofsky Performance Scale) of ≥ 60%.
  • 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 anticancer therapy within 28 days of nitrosoureas or mitomycin C within 42 days, a small molecule kinase inhibitor or non-cytotoxic hormonal agent within 7 days or 5 half-lives of the drug or active metabolites, another investigational agent within 28 days, radiation therapy within 42 days of the first scheduled dose of XL184.
  • The subject has received more than two prior antitumor therapies, including initial treatment and treatment for one prior relapse.
  • The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan.
  • 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 antineoplastic agents, investigational drugs, or other medications that were administered before study enrollment.
  • The subject is pregnant or breast-feeding.
  • The subject has an infection requiring systemic treatment.
  • The subject has a known allergy or hypersensitivity to any of the components of the XL184 formulation.
  • 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 or myocardial infarction within the past 6 months.
  • The subject has had another diagnosis of malignancy (unless nonmelanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed > 5 years ago and has no evidence of disease for 5 years before screening for this study).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00704288

Contacts
Contact: Exelixis Contact Line 1-866-939-4041

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
United States, Texas
University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Virginia
University of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Goga Radakovi         GR2P@hscmail.mcc.virginia.edu    
Sponsors and Collaborators
Exelixis
  More Information

No publications provided

Responsible Party: Exelixis, Inc. ( Yifah Yaron, MD, PhD/Director, Clinical Research )
Study ID Numbers: XL184-201
Study First Received: June 20, 2008
Last Updated: June 23, 2009
ClinicalTrials.gov Identifier: NCT00704288     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Exelixis:
GBM
Malignant gliomas

Study placed in the following topic categories:
Neuroectodermal Tumors
Glioblastoma
Astrocytoma
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Glioblastoma Multiforme
Glioma
Recurrence
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Neuroectodermal Tumors
Glioblastoma
Neoplasms
Neoplasms by Histologic Type
Astrocytoma
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Glioma
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on July 06, 2009