A Study of XL765 (SAR245409) in Combination With Temozolomide With and Without Radiation in Adults With Malignant Gliomas
| Status: | Completed |
|---|---|
| Conditions: | Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 11/18/2012 |
| Start Date: | August 2008 |
| End Date: | February 2013 |
| Contact: | For site information, send an email with site number to |
| Email: | Contact-Us@sanofi-aventis.com |
A Phase 1 Dose-Escalation Study of XL765 (SAR245409) in Combination With Temozolomide With and Without Radiation in Subjects With Malignant Gliomas
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.
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
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