GlioblastomaPhase 1NCT01240460
Exploratory Study of XL765 (SAR245409) or XL147 (SAR245408) in Subjects With Recurrent Glioblastoma Who Are Candidates for Surgical Resection
A Phase 1 study testing XL765 (SAR245409) and XL147 (SAR245408) in people with Glioblastoma and Astrocytoma, Grade IV, run by Sanofi at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Astrocytoma, Grade IV
- What is being tested?
- XL765 (SAR245409) and XL147 (SAR245408)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2011to Jun 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- The subject has available archival tumor tissue from the time of initial diagnosis of GB that is designated for central laboratory analysis.
- The subject is ≥ 18 years old.
- The subject has a Karnofsky performance status (KPS) ≥ 60%.
- The subject has adequate organ and marrow function.
- The subject has adequate fasting plasma glucose levels and glycosylated hemoglobin levels.
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- The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
- 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.
- Women of childbearing potential must have a negative pregnancy test at screening.
Who cannot join
- The subject has confirmed secondary GB (ie, had a pathology-confirmed lower-grade glioma that subsequently recurred as a higher grade glioma).
- The subject's tumor has a predominance of WHO Grade IV oligoastrocytoma.
- The subject has received radiation therapy for GB within 12 weeks (≤ 84 days) before their first dose of study drug treatment.
- The subject has received specific types of anticancer therapy (should be discussed with the treating physician)
- 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).
- 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.
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- 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.
- 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
- The subject has a baseline corrected QT interval (QTc) > 460 ms.
- The subject is unable to undergo repeated magnetic resonance imaging (MRI) scans for any reason (eg, cardiac pacemaker or ferromagnetic metal implants).
- The subject is known to be positive for the human immunodeficiency virus (HIV). Note: HIV testing is not required for eligibility.
- 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).
- The subject is pregnant or breastfeeding.
- The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Investigational Site Number 840004
Boston, Massachusetts, 02115
Investigational Site Number 840001
Los Angeles, California, 90024
Investigational Site Number 840002
New York, New York, 10021
Investigational Site Number 840003
San Francisco, California, 94143
About this study
Official title: 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.
- Conditions
- Glioblastoma, Astrocytoma, Grade IV
- Being tested
- XL765 (SAR245409), XL147 (SAR245408)
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XL765 (SAR245409)Drug
Supplied as 10-mg and/or 50-mg capsules
XL147 (SAR245408)Drug
Supplied as 100-mg, 150-mg and/or 200-mg tablets
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Twice-daily dosing (every 12 hours) XL765 Receives: Drug: XL765 (SAR245409) |
| 2 | Experimental | Once-daily dosing XL147 Receives: Drug: XL147 (SAR245408) |
| 3 | Experimental | Once-daily dosing XL765 Receives: Drug: XL765 (SAR245409) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To explore the biological effect of XL765 and XL147 measured by modulation of PI3K/ mTOR pathway readouts in GB tumor tissue
Measured: Assessed between 10 and 28 days after initiation of study drug
Secondary outcomes (7)
To examine the safety profile of daily oral administration of XL765 and XL147 in subjects with recurrent GB
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Duration of the study (approximately 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2010 (estimated)
- Study startJan 2011
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01240460
- Sponsor's protocol ID
- TED11605
- Other IDs
- XL765-202
- Status last verified
- Jul 2012
- First submitted
- 11 Nov 2010
- Last updated
- 27 Jul 2012
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Pharmacodynamic Study of XL765 and XL147 Administered as Single Agents to Subjects With Recurrent Glioblastoma Who Are Candidates for Surgical Resection
- ClinicalTrials.gov ID
- NCT01240460
- Acronym / sponsor ID
- TED11605
- Conditions
- Glioblastoma, Astrocytoma, Grade IV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Jan 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 15 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: XL765 (SAR245409)Twice-daily dosing (every 12 hours) XL765 |
| 2 | Experimental | Drug: XL147 (SAR245408)Once-daily dosing XL147 |
| 3 | Experimental | Drug: XL765 (SAR245409)Once-daily dosing XL765 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
- The subject has available archival tumor tissue from the time of initial diagnosis of GB that is designated for central laboratory analysis.
- The subject is ≥ 18 years old.
- The subject has a Karnofsky performance status (KPS) ≥ 60%.
- The subject has adequate organ and marrow function.
Key exclusion criteria (18 listed)
- The subject has confirmed secondary GB (ie, had a pathology-confirmed lower-grade glioma that subsequently recurred as a higher grade glioma).
- The subject's tumor has a predominance of WHO Grade IV oligoastrocytoma.
- The subject has received radiation therapy for GB within 12 weeks (≤ 84 days) before their first dose of study drug treatment.
- The subject has received specific types of anticancer therapy (should be discussed with the treating physician)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XL765 (SAR245409)Supplied as 10-mg and/or 50-mg capsules | Drug | 1, 3 |
| XL147 (SAR245408)Supplied as 100-mg, 150-mg and/or 200-mg tablets | Drug | 2 |
Primary outcome
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
7 secondary outcomes
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
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
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
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
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
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
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing XL765 (SAR245409) and XL147 (SAR245408) in people with Glioblastoma and Astrocytoma, Grade IV, run by Sanofi at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2012.