Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme

January 9, 2024 updated by: Exelixis

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

222

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University, The Preston Robert Tisch Brain Tumor Center
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas M.D. Anderson Cancer Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A cabozantinib 175 mg
cabozantinib, 175 mg, taken orally once per day (qd).
Drug: XL184
Gelatin capsules supplied in 25-mg and 100-mg strengths; continuous daily dosing
Experimental: Group B cabozantinib 125 mg
cabozantinib, 125 mg, taken orally once per day (qd).
Drug: XL184
Gelatin capsules supplied in 25-mg and 100-mg strengths; continuous daily dosing
Experimental: Group C 125 mg
cabozantinib, 125 mg, taken orally once per day (qd).
Drug: XL184
Gelatin capsules supplied in 25-mg and 100-mg strengths; continuous daily dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: 8 weeks until progressive disease
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Objective Response (Months)
Time Frame: Assessed during periodically scheduled visits until progressive disease
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
Progression Free Survival (PFS)
Time Frame: Assessed during periodically scheduled visits until progressive disease
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
Overall Survival (OS)
Time Frame: Assessed during periodically scheduled visits until progressive disease
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Exelixis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

June 20, 2008

First Submitted That Met QC Criteria

June 20, 2008

First Posted (Estimated)

June 24, 2008

Study Record Updates

Last Update Posted (Estimated)

February 5, 2024

Last Update Submitted That Met QC Criteria

January 9, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XL184-201

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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