GlioblastomaPhase 1NCT00960492

Safety Study of XL184 (Cabozantinib) in Combination With Temozolomide and Radiation Therapy in the Initial Treatment of Adults With Glioblastoma

A Phase 1 study testing XL184, temozolomide and Radiation Therapy in people with Glioblastoma and Giant Cell Glioblastoma, run by Exelixis at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Glioblastoma, Giant Cell Glioblastoma, Gliosarcoma
What is being tested?: XL184, temozolomide and Radiation Therapy
Type of treatment: Pill or oral medicine, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 8 sitesUnited States
Study dates: Sep 2009to Oct 2013
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Histologically confirmed diagnosis of Grade 4 astrocytic tumor, which includes glioblastoma, giant cell glioblastoma, gliosarcoma, and glioblastoma with oligodendroglial components.
Must have had a partial or complete surgical resection of the Grade 4 astrocytic tumor.
Subjects in Arm 1 must have had no previous treatment except surgery (ie, no previous RT, local chemotherapy, or systemic therapy). Subjects must meet certain other eligibility requirements.
Subjects in Arm 2 must have completed a standard first line regimen of concurrent TMZ and RT for newly diagnosed GB, followed by a rest phase, and has not had any other previous treatment except surgery (including any other regimens of RT and local or systemic chemotherapy). Subjects must meet certain other eligibility requirements.
Subjects must be able to undergo serial MRIs (computerized tomography [CT] may not substitute for magnetic resonance imaging [MRI]).
Must be ≥ 18 years old.

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Must have a Karnofsky performance status of ≥ 70% and the ability to swallow whole capsules
Must have no other diagnosis of malignancy (except surgically excised non-melanoma skin cancer or carcinoma in situ of the cervix, treated early stage prostate cancer, or a malignancy diagnosed ≥ 2 years previously with no current evidence of disease and no therapy within two years prior to enrollment on this study).
Must be capable of understanding and complying with the protocol requirements and has signed the informed consent document.
Sexually active fertile subjects (male and female) must agree to use accepted methods of contraception during the course of the study and for 3 months after the last dose of study drug(s).
Female subjects of childbearing potential must have a negative pregnancy test at screening.

Who cannot join

Subject has received prior systemic chemotherapy or RT (Arm 1) or prior systemic chemotherapy other than TMZ (Arm 2), biologic agents, or any other type of investigational agent for the treatment of brain tumors. Subjects who have progressed on TMZ are not eligible.
Subject has evidence of acute intracranial or intratumoral hemorrhage > Grade 1 either by MRI or CT scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study.
Subject has serious intercurrent illness such as: hypertension despite optimal treatment, or significant cardiac arrhythmias; or a recent history of serious disease such as symptomatic congestive heart failure, or abdominal fistula or gastrointestinal (GI) perforation within 6 months, prior to starting study treatment.
Subject has had major surgery within 28 days prior to starting study treatment, or had non water-tight dural closure during previous surgery, or has unhealed wounds from previous surgery.
Subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
Subject is pregnant or breastfeeding.

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Subject is known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at screening is not required).
Subject has a previously-identified allergy or hypersensitivity to components of either the XL184 or TMZ formulations.
Subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

United States8 sites

Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
University of Virginia Health System/Division of Neuro-Oncology
Charlottesville, Virginia, 22908
Henry Ford Health System
Detroit, Michigan, 48202
Duke University Medical Center; The Preston Robert Tisch Brain Tumor Center
Durham, North Carolina, 27710
MD Anderson Cancer Center
Houston, Texas, 77030
UCLA
Los Angeles, California, 90095
Beth Israel Medical Center
New York, New York, 10003
University of Washington
Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase 1 Dose Finding Study of the Safety and Pharmacokinetics of XL184 Administered Orally in Combination With Temozolomide and Radiation Therapy in the First Line Treatment of Subjects With Glioblastoma

The purpose of this study is to determine the highest safe dose of XL184 administered orally in combination with temozolomide (TMZ, Temodar®) and radiation therapy (RT). XL184 is a new chemical entity that inhibits VEGFR2, MET, and RET, kinases implicated in tumor formation, growth and migration. Temozolomide (TMZ, Temodar®) is an orally administered alkylating agent. It is approved by the Food and Drug Administration (FDA) for the treatment of newly diagnosed glioblastoma (GB) patients when given in combination with radiation therapy (RT) followed by maintenance treatment. First-line treatment for patients with GB consists of a concurrent phase (6-7 weeks in duration) during which TMZ is given with RT, followed by a rest phase (4 weeks in duration; to allow for recovery from delayed toxicity, if present), and a maintenance phase, during which patients receive TMZ for approximately twelve 28-day cycles. To determine the highest safe dose, subjects will receive different amounts of XL184 at different times according to the phase of TMZ and radiation therapy. The first group of subjects will receive the lowest dose of XL184. As long as no medically unacceptable side effects are noted, the dose will be increased for the next group. If the dose is not well-tolerated by the first group of subjects, the dose will be lowered for the next group.

Conditions: Glioblastoma, Giant Cell Glioblastoma, Gliosarcoma
Being tested: XL184, temozolomide, Radiation Therapy
Keywords: Astrocytic tumor, Glioblastoma with oligodendroglial components
Medical subject headings: Glioblastoma, Gliosarcoma, Astrocytoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

XL184Drug
XL184 will be administered daily as a single oral agent supplied as 25- and 100-mg capsules
temozolomideDrug
Also called Temodar®
TMZ will be supplied as 5-, 20-, 100-, 250-, 140-, and 180-mg capsules. The starting dose will be 75 mg/m2/day given daily with concurrent RT for 6 weeks
temozolomideDrug
Also called Temodar®
TMZ will be supplied as 5-, 20-, 100-, 250-, 140-, and 180-mg capsules. The starting dose will be 200 mg/m2/day given for 5 consecutive days and repeated every 28 days.
Radiation TherapyRadiation
Subjects will receive RT consisting of fractionated focal irradiation administered using 1.8-2 Gy/fraction, daily for 5 days/week for 6-7 weeks, for a total dose of up to 60 Gy.
temozolomideDrug
Also called Temodar®
TMZ will be supplied as 5-, 20-, 100-, 250-, 140-, and 180-mg capsules.

Study groups in NCT00960492
Study group	Role	What they receive
Arm 1	Experimental	XL184 will be initiated at the start of the 6-7 week concurrent phase of RT (+TMZ; some subjects found to have specific gene activity in their tumor tissue may not receive TMZ), given as a single agent during the rest phase (4 weeks), if applicable, and continued subsequently in the maintenance phase. Receives: Drug: XL184; Drug: temozolomide; Radiation: Radiation Therapy
Arm 2	Experimental	XL184 will be initiated during the maintenance phase with TMZ Receives: Drug: XL184; Drug: temozolomide
MTD Expansion	Experimental	XL184 will be initiated at the start of the 6-7 week concurrent phase of RT (+TMZ; some subjects found to have specific gene activity in their tumor tissue may not receive TMZ), given as a single agent in the rest phase (4 weeks), if applicable, and continued subsequently in the maintenance phase. Subjects in this group will receive XL184 and TMZ at the maximally tolerated dose levels determined in Arms 1 and 2. Receives: Drug: XL184; Drug: temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

Evaluate the safety and tolerability of oral administration of XL184 added to first-line treatment for subjects with newly diagnosed GB
Measured: Assessed at every visit to the study clinic
Determine the maximum tolerated dose (MTD) of oral XL184 when added to the concurrent phase of treatment with TMZ and RT and when added to the maintenance phase of treatment with TMZ for subjects with newly diagnosed GB
Measured: Assessed periodically as subjects are dose-escalted
Determine the safety and tolerability of XL184 when administered in combination with first-line treatment throughout the concurrent, rest and maintenance phases in an expanded MTD cohort
Measured: Assessed at each visit to the study center

Secondary outcomes (3)

Evaluate the plasma pharmacokinetics of XL184 and TMZ when XL184 is administered in combination with TMZ, and of XL184 when it is administered alone, in subjects with newly diagnosed GB
Measured: Assessed at 4 visits during the concurrent phase, 2 visits during the first maintenance phase cycle, and approximately every 4 weeks thereafter
Evaluate the pharmacodynamic effects of XL184 (with or without TMZ) and RT in the first line treatment of subjects with GB.
Measured: Assessed at 4 visits during the concurrent phase, 2 visits during the first maintenance phase cycle, and approximately every 4 weeks thereafter
Evaluate the preliminary efficacy of XL184 (with or without TMZ) and RT in the MTD expansion cohort in the first line treatment of subjects with GB
Measured: Assessed at 10 weeks and approximately every 4 weeks thereafter

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2009Oct 2013

First posted17 Aug 2009 (estimated)
Study startSep 2009
Primary completionNov 2012
Study completionOct 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for GlioblastomaStudies of the same condition, open and under way.
More trials run by ExelixisThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00960492
Sponsor's protocol ID: XL184-002
Status last verified: Sep 2014
First submitted: 13 Aug 2009
Last updated: 22 Sep 2014
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Glioblastoma trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Dose Finding Study of the Safety and Pharmacokinetics of XL184 Administered Orally in Combination With Temozolomide and Radiation Therapy in the First Line Treatment of Subjects With Glioblastoma
ClinicalTrials.gov ID: NCT00960492
Acronym / sponsor ID: XL184-002
Conditions: Glioblastoma, Giant Cell Glioblastoma, Gliosarcoma
Keywords: Astrocytic tumor, Glioblastoma with oligodendroglial components
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: ExelixisIndustry (pharma, biotech, devices)
Study start: Sep 2009
Primary completion: Nov 2012 (actual)
Study completion: Oct 2013 (actual)
First posted: 17 Aug 2009 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Arm 1	Experimental	Drug: XL184, Drug: temozolomide, Radiation: Radiation TherapyXL184 will be initiated at the start of the 6-7 week concurrent phase of RT (+TMZ; some subjects found to have specific gene activity in their tumor tissue may not receive TMZ), given as a single agent during the rest phase (4 weeks), if applicable, and continued subsequently in the maintenance phase.
Arm 2	Experimental	Drug: XL184, Drug: temozolomideXL184 will be initiated during the maintenance phase with TMZ
MTD Expansion	Experimental	Drug: XL184, Drug: temozolomideXL184 will be initiated at the start of the 6-7 week concurrent phase of RT (+TMZ; some subjects found to have specific gene activity in their tumor tissue may not receive TMZ), given as a single agent in the rest phase (4 weeks), if applicable, and continued subsequently in the maintenance phase. Subjects in this group will receive XL184 and TMZ at the maximally tolerated dose levels determined in Arms 1 and 2.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Histologically confirmed diagnosis of Grade 4 astrocytic tumor, which includes glioblastoma, giant cell glioblastoma, gliosarcoma, and glioblastoma with oligodendroglial components.
Must have had a partial or complete surgical resection of the Grade 4 astrocytic tumor.
Subjects in Arm 1 must have had no previous treatment except surgery (ie, no previous RT, local chemotherapy, or systemic therapy). Subjects must meet certain other eligibility requirements.
Subjects in Arm 2 must have completed a standard first line regimen of concurrent TMZ and RT for newly diagnosed GB, followed by a rest phase, and has not had any other previous treatment except surgery (including any other regimens of RT and local or systemic chemotherapy). Subjects must meet certain other eligibility requirements.
Subjects must be able to undergo serial MRIs (computerized tomography [CT] may not substitute for magnetic resonance imaging [MRI]).

Key exclusion criteria (9 listed)

Subject has received prior systemic chemotherapy or RT (Arm 1) or prior systemic chemotherapy other than TMZ (Arm 2), biologic agents, or any other type of investigational agent for the treatment of brain tumors. Subjects who have progressed on TMZ are not eligible.
Subject has evidence of acute intracranial or intratumoral hemorrhage > Grade 1 either by MRI or CT scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study.
Subject has serious intercurrent illness such as: hypertension despite optimal treatment, or significant cardiac arrhythmias; or a recent history of serious disease such as symptomatic congestive heart failure, or abdominal fistula or gastrointestinal (GI) perforation within 6 months, prior to starting study treatment.
Subject has had major surgery within 28 days prior to starting study treatment, or had non water-tight dural closure during previous surgery, or has unhealed wounds from previous surgery.
Subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
XL184XL184 will be administered daily as a single oral agent supplied as 25- and 100-mg capsules	Drug	Arm 1, Arm 2, MTD Expansion
temozolomideAlso: Temodar®TMZ will be supplied as 5-, 20-, 100-, 250-, 140-, and 180-mg capsules. The starting dose will be 75 mg/m2/day given daily with concurrent RT for 6 weeks	Drug	Arm 1
temozolomideAlso: Temodar®TMZ will be supplied as 5-, 20-, 100-, 250-, 140-, and 180-mg capsules. The starting dose will be 200 mg/m2/day given for 5 consecutive days and repeated every 28 days.	Drug	Arm 2
Radiation TherapySubjects will receive RT consisting of fractionated focal irradiation administered using 1.8-2 Gy/fraction, daily for 5 days/week for 6-7 weeks, for a total dose of up to 60 Gy.	Radiation	Arm 1
temozolomideAlso: Temodar®TMZ will be supplied as 5-, 20-, 100-, 250-, 140-, and 180-mg capsules.	Drug	MTD Expansion

Primary outcome

Evaluate the safety and tolerability of oral administration of XL184 added to first-line treatment for subjects with newly diagnosed GB
Time frame: Assessed at every visit to the study clinic
Determine the maximum tolerated dose (MTD) of oral XL184 when added to the concurrent phase of treatment with TMZ and RT and when added to the maintenance phase of treatment with TMZ for subjects with newly diagnosed GB
Time frame: Assessed periodically as subjects are dose-escalted
Determine the safety and tolerability of XL184 when administered in combination with first-line treatment throughout the concurrent, rest and maintenance phases in an expanded MTD cohort
Time frame: Assessed at each visit to the study center

3 secondary outcomes

Evaluate the plasma pharmacokinetics of XL184 and TMZ when XL184 is administered in combination with TMZ, and of XL184 when it is administered alone, in subjects with newly diagnosed GB
Time frame: Assessed at 4 visits during the concurrent phase, 2 visits during the first maintenance phase cycle, and approximately every 4 weeks thereafter
Evaluate the pharmacodynamic effects of XL184 (with or without TMZ) and RT in the first line treatment of subjects with GB.
Time frame: Assessed at 4 visits during the concurrent phase, 2 visits during the first maintenance phase cycle, and approximately every 4 weeks thereafter
Evaluate the preliminary efficacy of XL184 (with or without TMZ) and RT in the MTD expansion cohort in the first line treatment of subjects with GB
Time frame: Assessed at 10 weeks and approximately every 4 weeks thereafter

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2014.

Related trials for Glioblastoma

Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

8 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing XL184, temozolomide and Radiation Therapy in people with Glioblastoma and Giant Cell Glioblastoma, run by Exelixis at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the safety and tolerability of oral administration of XL184 added to first-line treatment for subjects with newly diagnosed GB (time frame: Assessed at every visit to the study clinic). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00960492.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2014.