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Completed

NCT Number: NCT00704080

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

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Key information

Conditions

Mixed Gliomas Astrocytoma Glioblastoma Glioblastoma Multiforme Glioma Malignant Gliomas Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Investigational Site Number, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

XL765 (SAR245409)

Drug

Gelatin capsules supplied in 5-mg, 10-mg, and 50-mg strengths; continuous daily dosing

Temozolomide

Drug

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 names: Temodar®

Primary outcomes

  1. 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 outcomes

  1. To evaluate plasma pharmacokinetics and pharmacodynamic effects of XL765 and temozolomide when administered in combination

    Time frame: Assessed during periodic visits

  2. To evaluate preliminary efficacy of XL765 in combination with temozolomide in adults with anaplastic gliomas or glioblastoma

    Time frame: Assessed during periodic visits

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Registry information

Official study title

A Phase 1 Dose-Escalation Study of XL765 (SAR245409) in Combination With Temozolomide With and Without Radiation in Subjects With Malignant Gliomas

Important dates

Study start
2008
Primary completion
2012
Study completion
2013
First posted
Jun 24, 2008
Registry last updated
Apr 10, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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