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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.
Information provided by (Responsible Party):
Sanofi Identifier:
First received: June 20, 2008
Last updated: April 9, 2013
Last verified: April 2013
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.

Condition Intervention Phase
Mixed Gliomas
Malignant Gliomas
Glioblastoma Multiforme
Drug: XL765 (SAR245409)
Drug: Temozolomide
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-Escalation Study of XL765 (SAR245409) in Combination With Temozolomide With and Without Radiation in Subjects With Malignant Gliomas

Resource links provided by NLM:

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 54
Study Start Date: August 2008
Study Completion Date: February 2013
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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®


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00704080

United States, Alabama
Investigational Site Number
Birmingham, Alabama, United States, 35205
United States, California
Investigational Site Number
Los Angeles, California, United States, 90024
United States, Massachusetts
Investigational Site Number
Boston, Massachusetts, United States, 02115
United States, New York
Investigational Site Number
New York, New York, United States, 10021
Investigational Site Number
Rochester, New York, United States, 14642
United States, Ohio
Investigational Site Number
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Responsible Party: Sanofi Identifier: NCT00704080     History of Changes
Other Study ID Numbers: TED11441
XL765-002 ( Other Identifier: (other study code) )
Study First Received: June 20, 2008
Last Updated: April 9, 2013

Keywords provided by Sanofi:
Anaplastic glioma

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents processed this record on April 25, 2017