Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme

Glioblastoma Multiforme Clinical Trial

Official title:

A Phase 2 Study of XL184 in Subjects With Progressive or Recurrent Glioblastoma Multiforme in First or Second Relapse

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00704288
• Other study ID #: XL184-201
• Status: Completed
• Phase: Phase 2
• Start date: May 2008
• Est. completion date: December 2012

Study information

• Verified date: January 2024
• Source: Exelixis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 222
• Est. completion date: December 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• XL184
Gelatin capsules supplied in 25-mg and 100-mg strengths; continuous daily dosing

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University, The Preston Robert Tisch Brain Tumor Center	Durham	North Carolina
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	University of California, Los Angeles	Los Angeles	California
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	Response and progression were determined per modified MacDonald Criteria and modified RANO criteria for GBM using imaging and clinical features	8 weeks until progressive disease
Secondary	Duration of Objective Response (Months)	Duration of response is defined as the time from the first documentation of objective response that was subsequently confirmed at a visit that was = 28 days later to disease progression or death due to any cause.	Assessed during periodically scheduled visits until progressive disease
Secondary	Progression Free Survival (PFS)	Response and progression were determined per modified MacDonald Criteria and modified RANO criteria for GBM using imaging and clinical features	Assessed during periodically scheduled visits until progressive disease
Secondary	Overall Survival (OS)	Overall survival (OS) is defined as the time from first dose to death due to any cause.	Assessed during periodically scheduled visits until progressive disease