A Study of XL765 in Combination With Temozolomide in Adults With Malignant Gliomas - Full Text View

Sponsored by:	Exelixis
Information provided by:	Exelixis
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 Temozolamide 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 Drug: Temozolomide	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide Gelatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title:	A Phase 1 Dose-Escalation Study of XL765 in Combination With Temozolomide in Subjects With Malignant Gliomas

Further study details as provided by Exelixis:

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:	65
Study Start Date:	June 2008
Estimated Study Completion Date:	November 2009
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: XL765 Gelatin capsules supplied in 5-mg, 10-mg, and 50-mg strenths; 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

Eligibility

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

Criteria

Inclusion Criteria:

Histologically confirmed intracranial anaplastic glioma or glioblastoma
Currently on a temozolomide dose of 200 mg/m2/day administered on Days 1-5 of a 28-day cycle for at least 4 weeks, 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 least18 years old.
Both men and women must practice adequate contraception
Informed consent

Exclusion Criteria:

Progressed while on temozolomide.
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 and/or mTOR inhibitors, radiation therapy
Not recovered from the toxic effects of prior therapy
Pregnant or breast feeding
History of diabetes mellitus.
Currently taking enzyme-inducing anticonvulsant medication or valproic acid
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: Exelixis Contact Line

1-866-939-4041

Locations

United States, California
University of California, Los Angeles	Recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Timothy Cloughesy, MD
United States, New York
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10021
Contact: Shilpa Patel 646-227-2206 patels@mskcc.org
Principal Investigator: Antonio Omuro, MD

Sponsors and Collaborators

Exelixis

More Information

Responsible Party:	Exelixis, Inc. ( Ron Shazer, MD/Director, Clinical Research )
Study ID Numbers:	XL765-002
Study First Received:	June 20, 2008
Last Updated:	October 20, 2008
ClinicalTrials.gov Identifier:	NCT00704080
Health Authority:	United States: Food and Drug Administration

Keywords provided by Exelixis:

GBM
Anaplastic glioma

Study placed in the following topic categories:

Neuroectodermal Tumors
Glioblastoma
Glioblastoma multiforme
Astrocytoma
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Glioma
Temozolomide
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Neoplasms, Nerve Tissue
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009