Exploratory Study of XL765 (SAR245409) or XL147 (SAR245408) in Subjects With Recurrent Glioblastoma Who Are Candidates for Surgical Resection

July 26, 2012 updated by: Sanofi

An Exploratory Pharmacodynamic Study of XL765 and XL147 Administered as Single Agents to Subjects With Recurrent Glioblastoma Who Are Candidates for Surgical Resection

The purpose of this study is to measure what effect the study drug XL765 (SAR245409) or the study drug XL147 (SAR245408) has on tumor tissue in subjects with recurrent glioblastoma (GB) who are candidates for surgical resection. XL765 (SAR245409) and XL147 (SAR245408), the two investigational agents examined in this study, XL147 (SAR245408) is a potent inhibitor of PI3 Kinase (PI3K) and XL765 (SAR245409) is a dual PI3K and mTOR inhibitor. In preclinical studies, inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90024
        • Investigational Site Number 840001
      • San Francisco, California, United States, 94143
        • Investigational Site Number 840003
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Investigational Site Number 840004
    • New York
      • New York, New York, United States, 10021
        • Investigational Site Number 840002

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. The subject has histologically confirmed diagnosis of primary GB for which the subject has received prior treatment, including radiation and/or chemotherapy, and will be undergoing a second surgical resection.
  2. The subject has available archival tumor tissue from the time of initial diagnosis of GB that is designated for central laboratory analysis.
  3. The subject is ≥ 18 years old.
  4. The subject has a Karnofsky performance status (KPS) ≥ 60%.
  5. The subject has adequate organ and marrow function.
  6. The subject has adequate fasting plasma glucose levels and glycosylated hemoglobin levels.
  7. The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
  8. Sexually active subjects (men and women) must agree to use medically-accepted barrier methods of contraception during the course of the study and for 3 months after the last dose of study drug, even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control.
  9. Women of childbearing potential must have a negative pregnancy test at screening.

Exclusion Criteria:

  1. The subject has confirmed secondary GB (ie, had a pathology-confirmed lower-grade glioma that subsequently recurred as a higher grade glioma).
  2. The subject's tumor has a predominance of WHO Grade IV oligoastrocytoma.
  3. The subject has received radiation therapy for GB within 12 weeks (≤ 84 days) before their first dose of study drug treatment.
  4. The subject has received specific types of anticancer therapy (should be discussed with the treating physician)
  5. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 Grade ≤ 1 from AEs due to surgery, radiation, antineoplastic agents, investigational drugs, or other medications that were administered before screening (except Grade 2 alopecia and Grade 2 lymphocytopenia).
  6. The subject is receiving > 1 mg/day warfarin (or equivalent of other coumarin derivatives) and is unable to switch to low molecular weight heparin within 14 days before the first dose of study drug.
  7. The subject is receiving enzyme-inducing anti-epileptic agents (EIAED; eg, carbamazepine, phenytoin, phenobarbital, or primidone) or valproic acid and is unable to convert to EIAED anti-seizure agents within 14 days before the first dose of study drug.

  8. The subject has uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection
    • Hypertension (consistent blood pressure readings of > 140 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment
    • Significant cardiac arrhythmias, or a recent history of serious disease, such as either symptomatic congestive heart failure or unstable angina pectoris within 3 months, or the following events within 6 months: myocardial infarction, stroke, or transient ischemic attack.
    • Inherited or acquired bleeding diathesis
  9. The subject has a baseline corrected QT interval (QTc) > 460 ms.
  10. The subject is unable to undergo repeated magnetic resonance imaging (MRI) scans for any reason (eg, cardiac pacemaker or ferromagnetic metal implants).
  11. The subject is known to be positive for the human immunodeficiency virus (HIV). Note: HIV testing is not required for eligibility.
  12. The subject has impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study treatment (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  13. The subject is pregnant or breastfeeding.
  14. The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 1
Twice-daily dosing (every 12 hours) XL765
Drug: XL765 (SAR245409)
Supplied as 10-mg and/or 50-mg capsules
Experimental: 2
Once-daily dosing XL147
Drug: XL147 (SAR245408)
Supplied as 100-mg, 150-mg and/or 200-mg tablets
Experimental: 3
Once-daily dosing XL765
Drug: XL765 (SAR245409)
Supplied as 10-mg and/or 50-mg capsules

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
To explore the biological effect of XL765 and XL147 measured by modulation of PI3K/ mTOR pathway readouts in GB tumor tissue
Time Frame: Assessed between 10 and 28 days after initiation of study drug
Assessed between 10 and 28 days after initiation of study drug

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
To examine the safety profile of daily oral administration of XL765 and XL147 in subjects with recurrent GB
Time Frame: Assessed at every visit to the study clinic for the duration of subject's treatment
Assessed at every visit to the study clinic for the duration of subject's treatment
To determine the levels of XL765 and XL147 in plasma and GB tumor tissue
Time Frame: Assessed at periodic visits between 10 and 28 days after initiation of study drug for the duration of subject's treatment
Assessed at periodic visits between 10 and 28 days after initiation of study drug for the duration of subject's treatment
To assess the anti-proliferative and pro-apoptotic effects of XL765 and XL147 on tumor cells
Time Frame: Assessed at periodic visits to the study clinic for the duration of subject's treatment
Assessed at periodic visits to the study clinic for the duration of subject's treatment
To measure changes in tumor after surgery in subjects receiving XL765 and XL147
Time Frame: Assessed at periodic visits following surgery 10 to 28 days after initiation of study drug for the duration of subject's treatment
Assessed at periodic visits following surgery 10 to 28 days after initiation of study drug for the duration of subject's treatment
To conduct genetic analyses of GB tumor tissue comparing, where feasible, tumor tissue removed during the on-study resection with tissue removed during the initial surgical resection
Time Frame: Assessed 10 to 28 days after initiation of study drug
Assessed 10 to 28 days after initiation of study drug
To evaluate the pharmacodynamic effects of XL765 and XL147 in blood and/or blood cells for identification and characterization of surrogate biomarkers associated with the biological effects of XL765 and XL147
Time Frame: Assessed at periodic visits to the study clinic
Assessed at periodic visits to the study clinic
To explore the relationship between clinical response and genomic and proteomic biomarkers in the PI3K and EGFR pathways
Time Frame: Duration of the study (approximately 2 years)
Duration of the study (approximately 2 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sanofi

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 11, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 12, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 15, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 27, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 26, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TED11605
  • XL765-202 (Other Identifier: other study code)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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