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

Sanofi

Status and phase: Completed; Phase 1

Conditions: Glioblastoma Multiforme; Mixed Gliomas; Malignant Gliomas

Treatments: Drug: XL765 (SAR245409); Drug: Temozolomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT00704080

XL765-002 (Other Identifier)

TED11441

Details and patient eligibility

About

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.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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54 participants in 1 patient group

1

Experimental group

Treatment:

Drug: Temozolomide

Drug: XL765 (SAR245409)