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

NCT00704080 | Completed Phase 1

• 2 other identifiers: TED11441XL765-002
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 6

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

Keywords

GBM; Anaplastic glioma

Outcome Measures

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

  Assessed at each visit/periodic visits

Secondary Outcomes (2)

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

  Assessed during periodic visits

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

  Assessed during periodic visits

Study Arms (1)

1

EXPERIMENTAL

Drug: XL765 (SAR245409); Drug: Temozolomide

Interventions

XL765 (SAR245409) DRUG

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

1

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

Also known as: Temodar®

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (6)

Investigational Site Number

Birmingham, Alabama, 35205, United States

Location

Investigational Site Number

Los Angeles, California, 90024, United States

Location

Investigational Site Number

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number

New York, New York, 10021, United States

Location

Investigational Site Number

Rochester, New York, 14642, United States

Location

Investigational Site Number

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

XL765; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2008
• First Posted: June 24, 2008
• Study Start: August 1, 2008
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2013
• Last Updated: April 10, 2013

Record last verified: 2013-04

Locations

US (6)