A Study of XL765 (SAR245409) in Combination With Temozolomide With and Without Radiation in Adults With Malignant Gliomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00704080
Recruitment Status : Completed
First Posted : June 24, 2008
Last Update Posted : April 10, 2013
Information provided by (Responsible Party):

June 20, 2008
June 24, 2008
April 10, 2013
August 2008
February 2012   (Final data collection date for primary outcome measure)
Safety, tolerability, and maximum tolerated dose of XL765 administered in combination with temozolomide in subjects with anaplastic gliomas or glioblastoma currently stable on a maintenance temozolomide dose [ Time Frame: Assessed at each visit/periodic visits ]
Same as current
Complete list of historical versions of study NCT00704080 on Archive Site
  • To evaluate plasma pharmacokinetics and pharmacodynamic effects of XL765 and temozolomide when administered in combination [ Time Frame: Assessed during periodic visits ]
  • To evaluate preliminary efficacy of XL765 in combination with temozolomide in adults with anaplastic gliomas or glioblastoma [ Time Frame: Assessed during periodic visits ]
Same as current
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A Study of XL765 (SAR245409) in Combination With Temozolomide With and Without Radiation in Adults With Malignant Gliomas
A Phase 1 Dose-Escalation Study of XL765 (SAR245409) in Combination With Temozolomide With and Without Radiation in Subjects With Malignant Gliomas
The purpose of this study is to determine the safety and tolerability of XL765 in combination with Temozolomide in adults with anaplastic gliomas or glioblastoma on a stable Temozolomide maintenance dose. XL765 is a new chemical entity that inhibits the kinases PI3K and mTOR. In preclinical studies, inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells, whereas inactivation of mTOR has been shown to inhibit the growth of tumor cells. Temozolomide (TMZ, Temodar®) is an orally administered alkylating agent with activity against malignant gliomas. It is approved by the Food and Drug Administration for the following indications: 1) treatment of newly diagnosed glioblastoma multiforme (GBM) patients when given concomitantly with radiotherapy and then as maintenance treatment; 2) refractory anaplastic astrocytoma (AA), ie, patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine. Temozolomide is commonly used in the treatment of other anaplastic gliomas (AG) including oligodendroglial tumors and mixed gliomas.
Not Provided
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Mixed Gliomas
  • Malignant Gliomas
  • Glioblastoma Multiforme
  • Drug: XL765 (SAR245409)
    Gelatin capsules supplied in 5-mg, 10-mg, and 50-mg strengths; continuous daily dosing
  • Drug: Temozolomide
    Capsules supplied in 5-mg, 20-mg, 100-mg, 140-mg, 180-mg, and 250-mg strengths; dosed at 200 mg/m2/day for 5 consecutive days, repeated every 28 days
    Other Name: Temodar®
Experimental: 1
  • Drug: XL765 (SAR245409)
  • Drug: Temozolomide
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
February 2013
February 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed intracranial Grade 3 or 4 anaplastic glioma or glioblastoma (astrocytic tumor, anaplastic oligodendroglioma, or oligoastrocytoma)
  • Received prior standard radiation for a Grade 3 or 4 astrocytic tumor with a minimum cumulative dose of 40 Gy administered
  • Completed at least one full cycle of temozolomide of 200 mg/m2/day administered on Days 1-5 of a 28-day cycle, without unacceptable toxicity or progression
  • Karnofsky performance status of 60 or more
  • Adequate organ and bone marrow function as defined by hematological and serum chemistry limits
  • At least 18 years old.
  • Both men and women must practice adequate contraception
  • Informed consent

Exclusion Criteria:

  • Progressed while on temozolomide
  • Evidence of acute intracranial or intratumoral hemorrhage > Grade 1
  • Restriction of some therapies/medications within specific timeframes prior to enrollment and during the study including cytotoxic chemotherapy other than temozolomide, biologic agents, nitrosoureas or mitomycin C, small-molecule kinase inhibitors, non-cytotoxic hormonal agents, prior therapy with a PI3K inhibitors, radiation therapy, enzyme-inducing anti-convulsants, valproic acid
  • Not recovered from the toxic effects of prior therapy
  • Pregnant or breast feeding
  • History of diabetes mellitus
  • Uncontrolled intercurrent illness
  • Congestive heart failure, unstable angina, or a myocardial infarction within 3 months of entering the study.
  • HIV positive
  • Diagnosis of another malignancy may exclude subject from study
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
XL765-002 ( Other Identifier: (other study code) )
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Study Director: Clinical Sciences & Operations Sanofi
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP