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

NCT ID: NCT00704080

Last Updated: 2013-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2013-02-28

Brief Summary

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.

Conditions

Mixed Gliomas; Malignant Gliomas; Glioblastoma Multiforme

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

XL765 (SAR245409)

Intervention Type: DRUG

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

Temozolomide

Intervention Type: 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

Interventions

XL765 (SAR245409)

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Temodar®

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number

Birmingham, Alabama, United States

Investigational Site Number

Los Angeles, California, United States

Investigational Site Number

Boston, Massachusetts, United States

Investigational Site Number

New York, New York, United States

Investigational Site Number

Rochester, New York, United States

Investigational Site Number

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

XL765-002

Identifier Type: OTHER

Identifier Source: secondary_id

TED11441

Identifier Type: -

Identifier Source: org_study_id