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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00704080
First received: June 20, 2008
Last updated: April 9, 2013
Last verified: April 2013

June 20, 2008
April 9, 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 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00704080 on ClinicalTrials.gov Archive Site
  • To evaluate plasma pharmacokinetics and pharmacodynamic effects of XL765 and temozolomide when administered in combination [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]
  • To evaluate preliminary efficacy of XL765 in combination with temozolomide in adults with anaplastic gliomas or glioblastoma [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
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
Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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
Interventions:
  • Drug: XL765 (SAR245409)
  • Drug: Temozolomide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
54
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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00704080
TED11441, XL765-002
Not Provided
Sanofi
Sanofi
Not Provided
Study Director: Clinical Sciences & Operations Sanofi
Sanofi
April 2013

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