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

Primary Purpose

Mixed Gliomas, Malignant Gliomas, Glioblastoma Multiforme

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
XL765 (SAR245409)
Temozolomide
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mixed Gliomas focused on measuring GBM, Anaplastic glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Investigational Site Number
  • Investigational Site Number
  • Investigational Site Number
  • Investigational Site Number
  • Investigational Site Number
  • Investigational Site Number

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Outcomes

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

Secondary Outcome Measures

To evaluate plasma pharmacokinetics and pharmacodynamic effects of XL765 and temozolomide when administered in combination
To evaluate preliminary efficacy of XL765 in combination with temozolomide in adults with anaplastic gliomas or glioblastoma

Full Information

First Posted
June 20, 2008
Last Updated
April 9, 2013
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT00704080
Brief Title
A Study of XL765 (SAR245409) in Combination With Temozolomide With and Without Radiation in Adults With Malignant Gliomas
Official Title
A Phase 1 Dose-Escalation Study of XL765 (SAR245409) in Combination With Temozolomide With and Without Radiation in Subjects With Malignant Gliomas
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
February 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mixed Gliomas, Malignant Gliomas, Glioblastoma Multiforme
Keywords
GBM, Anaplastic glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
XL765 (SAR245409)
Intervention Description
Gelatin capsules supplied in 5-mg, 10-mg, and 50-mg strengths; continuous daily dosing
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
Temodar®
Intervention Description
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
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
To evaluate plasma pharmacokinetics and pharmacodynamic effects of XL765 and temozolomide when administered in combination
Time Frame
Assessed during periodic visits
Title
To evaluate preliminary efficacy of XL765 in combination with temozolomide in adults with anaplastic gliomas or glioblastoma
Time Frame
Assessed during periodic visits

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35205
Country
United States
Facility Name
Investigational Site Number
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
Investigational Site Number
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Investigational Site Number
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Investigational Site Number
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Investigational Site Number
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

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

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