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

Glioblastoma Multiforme Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00704080
• Other study ID #: TED11441
• Secondary ID: XL765-002
• Status: Completed
• Phase: Phase 1
• First received: June 20, 2008
• Last updated: April 9, 2013
• Start date: August 2008
• Est. completion date: February 2013

Study information

• Verified date: April 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: February 2013
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme
• Glioma
• Malignant Gliomas
• Mixed Gliomas

Intervention

Drug:
• XL765 (SAR245409)
Gelatin capsules supplied in 5-mg, 10-mg, and 50-mg strengths; continuous daily dosing
• 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

Locations

Country	Name	City	State
United States	Investigational Site Number	Birmingham	Alabama
United States	Investigational Site Number	Boston	Massachusetts
United States	Investigational Site Number	Cleveland	Ohio
United States	Investigational Site Number	Los Angeles	California
United States	Investigational Site Number	New York	New York
United States	Investigational Site Number	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	To evaluate plasma pharmacokinetics and pharmacodynamic effects of XL765 and temozolomide when administered in combination		Assessed during periodic visits	No
Secondary	To evaluate preliminary efficacy of XL765 in combination with temozolomide in adults with anaplastic gliomas or glioblastoma		Assessed during periodic visits	No