CompletedPhase 1

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

United States26 participantsStarted 2009-09

Plain-language summary

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.

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * 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. * 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 …

What they're measuring

Evaluate the safety and tolerability of oral administration of XL184 added to first-line treatment for subjects with newly diagnosed GB

Timeframe: 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

Timeframe: 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

Timeframe: Assessed at each visit to the study center

Trial details

NCT IDNCT00960492

SponsorExelixis

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2012-11

View on ClinicalTrials.gov More Glioblastoma trials