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

Sponsor:	Sanofi-Aventis
Information provided by (Responsible Party):	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT00704080

Purpose

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 I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study 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:

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide

U.S. FDA Resources

Further study details as provided by Sanofi-Aventis:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate plasma pharmacokinetics and pharmacodynamic effects of XL765 and temozolomide when administered in combination [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]
To evaluate preliminary efficacy of XL765 in combination with temozolomide in adults with anaplastic gliomas or glioblastoma [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	September 2008
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	July 2013 (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®

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00704080

Contacts

Contact: For site information, send an email with site number to

Contact-Us@sanofi-aventis.com

Locations

United States, New York
Investigational Site Number 165464	Recruiting
New York, New York, United States, 10021

Sponsors and Collaborators

Sanofi-Aventis

Investigators

Study Director:

Clinical Sciences & Operations

Sanofi-Aventis

More Information

No publications provided

Responsible Party:	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT00704080 History of Changes
Other Study ID Numbers:	TED11441, XL765-002
Study First Received:	June 20, 2008
Last Updated:	September 19, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Sanofi-Aventis:

GBM
Anaplastic glioma

Additional relevant MeSH terms:

Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012