A Study of XL765 (SAR245409) in Combination With Temozolomide With and Without Radiation in Adults With Malignant Gliomas
This study has been completed.
Sponsor:
Sanofi
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00704080
First received: June 20, 2008
Last updated: April 9, 2013
Last verified: April 2013
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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 1 |
| 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:
Further study details as provided by Sanofi:
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 ]
| Enrollment: | 54 |
| Study Start Date: | August 2008 |
| Study Completion Date: | February 2013 |
| Primary Completion Date: | February 2012 (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
Locations
| United States, Alabama | |
| Investigational Site Number | |
| Birmingham, Alabama, United States, 35205 | |
| United States, California | |
| Investigational Site Number | |
| Los Angeles, California, United States, 90024 | |
| United States, Massachusetts | |
| Investigational Site Number | |
| Boston, Massachusetts, United States, 02115 | |
| United States, New York | |
| Investigational Site Number | |
| New York, New York, United States, 10021 | |
| Investigational Site Number | |
| Rochester, New York, United States, 14642 | |
| United States, Ohio | |
| Investigational Site Number | |
| Cleveland, Ohio, United States, 44195 | |
Sponsors and Collaborators
Sanofi
Investigators
| Study Director: | Clinical Sciences & Operations | Sanofi |
More Information
No publications provided
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT00704080 History of Changes |
| Other Study ID Numbers: | TED11441, XL765-002 |
| Study First Received: | June 20, 2008 |
| Last Updated: | April 9, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Sanofi:
|
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 May 16, 2013