GlioblastomaPhase 2NCT00672243
Ph II Erlotinib + Sirolimus for Pts w Recurrent Malignant Glioma Multiforme
A Phase 2 study testing Erlotinib + sirolimus in people with Glioblastoma and Gliosarcoma, run by Duke University at 1 site in United States.
Trial summary
Primary objective: To determine the 6-month progression free survival of patients with recurrent glioblastoma multiforme (GBM) treated with Erlotinib plus Sirolimus. Secondary objectives: To further define the safety and tolerability of Erlotinib plus Sirolimus when administered to patients with recurrent GBM; and to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Gliosarcoma
- What is being tested?
- Erlotinib + sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Dec 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Pts have confirmed diagnosis of recurrent primary WHO grade IV malignant glioma (MG). Pts w recurrent disease whose diagnostic pathology confirmed GBM will not need re-biopsy. Pts w prior low-gr glioma / anaplastic glioma are eligible if histologic assessment demonstrates transformation to GBM
- Age >18 yrs
- Interval of >2 wk between prior surgical resection
- Interval of >12 wks between prior external-beam radiation therapy (XRT) unless there is either: histopathologic confirmation of recurrent tumor; new enhancement on MRI outside of XRT treatment field; / progressive radiographic changes after XRT/temo as well as after adjuvant, post-XRT temo
- Interval of >4 wks between chemo \& enrollment on protocol unless: unequivocal evidence of tumor progression; \& pt has recovered fully from all toxicity associated w prior surgery, XRT/chemo. Pts treated w chemo agents such as VP-16 who would normally be retreated after shorter intervals may be treated at usual starting time even if <4 wks from last prior dose chemo
- Karnofsky performance score >= 70 percent
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- Hematocrit >29 percent, absolute neutrophil count (ANC) >1,500 cells/microliter, platelets >100,000 cells/microliter
- Serum creatinine <1.5 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) \& bilirubin <1.5 x upper limit of normal (ULN); fasting plasma triglyceride \& cholesterol < gr1
- For pts on corticosteroids, dose should not be increasing for >7 days prior to baseline Gd-MRI of brain if medically appropriate
- Pts in enzyme inducing antiepileptic drug cohort must be on stable dose of p450-inducing EIAED for >2 wks. Pts in non-EIAED cohort must not receive any p450-EIAED for >2 wks prior to \& during participation in trial
- Signed informed consent approved by Institutional Review Board (IRB) prior to pt entry
- If sexually active, pts will take contraceptive measures for duration of treatments \& for 3 months following discontinuation of Erlotinib
- Pts who have had prior bevacizumab are eligible however interval of >6 weeks must have elapsed since their last dose
Who cannot join
- Prior mammalian target of rapamycin (mTOR) directed therapy
- Prior epidermal growth factor receptor (EGFR)-directed therapy
- Female pts are pregnant/breast feeding, or adults of reproductive potential not employing effective method of birth control. Women of childbearing potential must have negative serum pregnancy test <72 hours prior to administration of Erlotinib
- Co-medication that may interfere w study results
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hyperlipidemia not controlled w medication, psychiatric illness/social situations that would limit compliance w study requirements,/disorders associated w significant immunocompromise
- Acute/chronic liver disease
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- Impairment of GI function/GI disease that may significantly alter absorption of Erlotinib
- Pts who have received investigational drugs <4 wks prior to entry on study or who have not recovered from toxic effects of such therapy
- Pts who have received biologic, immunotherapeutic/cytostatic agents <1 wk prior to entry on study/have not recovered from toxic effects of such therapy
- Pt is <5 yrs free of another primary malignancy except: if other primary malignancy is not currently clinically significant/requiring active intervention,/if other primary malignancy is basal cell skin cancer/cervical carcinoma in situ. Existence of any other malignant disease is not allowed
- Pts have had any surgery other than resection of brain tumor <2 wks prior to entry on study/have not recovered from side effects of such therapy
- Pts unwilling to/unable to comply w protocol
- Pts w acute/chronic renal insufficiency/those w acute renal insufficiency of any severity due to hepato-renal syndrome/in peri-operative liver transplantation period
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Health System
Durham, North Carolina, 27710
About this study
Official title: Phase II Trial of Erlotinib Plus Sirolimus for Patients With Recurrent Malignant Glioma Multiforme
Primary objective:
To determine the 6-month progression free survival of patients with recurrent glioblastoma multiforme (GBM) treated with Erlotinib plus Sirolimus.
Secondary objectives:
To further define the safety and tolerability of Erlotinib plus Sirolimus when administered to patients with recurrent GBM; and to evaluate progression free survival, radiographic response and overall survival of patients with recurrent GBM treated with Erlotinib plus Sirolimus.
Read the detailed description
The primary objective of this study will be to determine the 6-month progression free survival of patients with recurrent GBM treated with Erlotinib plus Sirolimus.
This is an exploratory, single-arm, phase II study designed to assess the anti-tumor activity of a combinatorial regimen consisting of Erlotinib plus Sirolimus among patients with recurrent GBM. The combinatorial regimen of Erlotinib plus Sirolimus is rationally designed to simultaneously inhibit upstream (EGFR) and downstream (mTOR) mediators of Phosphatidylinositide 3-kinase/Protein Kinase B (PI3/AKT) signaling. In a recently completed phase I study, we determined that an EGFR inhibitor (Gefitinib) can be safely combined with Sirolimus at dose levels that are routinely used in the monotherapy setting. Therefore, the primary endpoint of this study is the probability of progression-free survival at 6 months among recurrent GBM patients treated with standard doses of Erlotinib plus Sirolimus. An important secondary objective is to further assess the safety of Erlotinib and Sirolimus for patients with recurrent GBM.
- Conditions
- Glioblastoma, Gliosarcoma
- Being tested
- Erlotinib + sirolimus
- Keywords
- GBM, Brain tumor, Erlotinib, Sirolimus, Glioblastoma multiforme, Glioblastoma, Gliosarcoma3, Tarceva, Rapamune
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erlotinib + sirolimusDrug
Also called sirolimus - Rapamune, erlotinib - Tarceva - OSI-774
Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of oral erlotinib and 5mg of oral sirolimus for patients not on concurrent CY3PA-inducing anti-epileptics (EIAEDS) and 400 mg of oral erlotinib and 10 mg of oral sirolimus for patients on concurrent EIAEDS.
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib + Sirolimus | Experimental | Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of erlotinib and 5mg of sirolimus for patients not on concurrent Cytochrome P450, family 3 (CY3PA)-inducing anti-epileptics (EIAEDS) and 400 mg of erlotinib and 10 mg of sirolimus for patients on concurrent EIAEDS. Receives: Drug: Erlotinib + sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month Progression-free Survival (PFS)
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or death due to any cause. Progression based on Macdonald criteria is defined as a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.
Measured: 6 months
Secondary outcomes (4)
Median Progression Free Survival (PFS)
Time in weeks from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Progression based on Macdonald criteria is defined as a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.
Measured: 2 years
Median Overall Survival (OS)
Time in weeks from the start of study treatment to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Measured: 2 years
Best Radiographic Response
Best radiographic response per modified Macdonald criteria. Complete response: disappearance of all enhancing tumor, no new lesions, and no steroids or only maintenance doses. Partial response: ≥ 50% reduction in the products of the perpendicular diameters of all enhancing lesions, no new lesions, \& steroids must be at a stable/decreasing dose. Stable disease: does not qualify for complete or partial response or progression \& is stable clinically. Progression: ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions, any new lesion or clinical deterioration.
Measured: 2 years
Number of Participants Experiencing a ≥ Grade 3, Treatment-related, Non-hematologic Toxicity.
Number of participants experiencing a ≥ grade 3, treatment-related, non-hematologic toxicity.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2008 (estimated)
- Study startApr 2007
- Primary completionSep 2008
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., OSI Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- David Reardon, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00672243
- Sponsor's protocol ID
- Pro00000345
- Status last verified
- Jul 2013
- First submitted
- 29 Jan 2008
- Last updated
- 7 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Friedman AH, Herndon JE 2nd, Marcello J, Norfleet JA, McLendon RE, Sampson JH, Friedman HS. Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J Neurooncol. 2010 Jan;96(2):219-30. doi: 10.1007/s11060-009-9950-0. Epub 2009 Jun 28.
PubMed 19562254
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Erlotinib Plus Sirolimus for Patients With Recurrent Malignant Glioma Multiforme
- ClinicalTrials.gov ID
- NCT00672243
- Acronym / sponsor ID
- Pro00000345
- Conditions
- Glioblastoma, Gliosarcoma
- Keywords
- GBM, Brain tumor, Erlotinib, Sirolimus, Glioblastoma multiforme, Glioblastoma, Gliosarcoma3, Tarceva
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc., OSI Pharmaceuticals
- Study start
- Apr 2007
- Primary completion
- Sep 2008 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 6 May 2008 (estimated)
- Results
- Posted 4 Apr 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary objective:
To determine the 6-month progression free survival of patients with recurrent glioblastoma multiforme (GBM) treated with Erlotinib plus Sirolimus.
Secondary objectives:
To further define the safety and tolerability of Erlotinib plus Sirolimus when administered to patients with recurrent GBM; and to evaluate progression free survival, radiographic response and overall survival of patients with recurrent GBM treated with Erlotinib plus Sirolimus.
Detailed description
The primary objective of this study will be to determine the 6-month progression free survival of patients with recurrent GBM treated with Erlotinib plus Sirolimus.
This is an exploratory, single-arm, phase II study designed to assess the anti-tumor activity of a combinatorial regimen consisting of Erlotinib plus Sirolimus among patients with recurrent GBM. The combinatorial regimen of Erlotinib plus Sirolimus is rationally designed to simultaneously inhibit upstream (EGFR) and downstream (mTOR) mediators of Phosphatidylinositide 3-kinase/Protein Kinase B (PI3/AKT) signaling. In a recently completed phase I study, we determined that an EGFR inhibitor (Gefitinib) can be safely combined with Sirolimus at dose levels that are routinely used in the monotherapy setting. Therefore, the primary endpoint of this study is the probability of progression-free survival at 6 months among recurrent GBM patients treated with standard doses of Erlotinib plus Sirolimus. An important secondary objective is to further assess the safety of Erlotinib and Sirolimus for patients with recurrent GBM.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib + Sirolimus | Experimental | Drug: Erlotinib + sirolimusErlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of erlotinib and 5mg of sirolimus for patients not on concurrent Cytochrome P450, family 3 (CY3PA)-inducing anti-epileptics (EIAEDS) and 400 mg of erlotinib and 10 mg of sirolimus for patients on concurrent EIAEDS. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Pts have confirmed diagnosis of recurrent primary WHO grade IV malignant glioma (MG). Pts w recurrent disease whose diagnostic pathology confirmed GBM will not need re-biopsy. Pts w prior low-gr glioma / anaplastic glioma are eligible if histologic assessment demonstrates transformation to GBM
- Age >18 yrs
- Interval of >2 wk between prior surgical resection
- Interval of >12 wks between prior external-beam radiation therapy (XRT) unless there is either: histopathologic confirmation of recurrent tumor; new enhancement on MRI outside of XRT treatment field; / progressive radiographic changes after XRT/temo as well as after adjuvant, post-XRT temo
- Interval of >4 wks between chemo \& enrollment on protocol unless: unequivocal evidence of tumor progression; \& pt has recovered fully from all toxicity associated w prior surgery, XRT/chemo. Pts treated w chemo agents such as VP-16 who would normally be retreated after shorter intervals may be treated at usual starting time even if <4 wks from last prior dose chemo
Key exclusion criteria (13 listed)
- Prior mammalian target of rapamycin (mTOR) directed therapy
- Prior epidermal growth factor receptor (EGFR)-directed therapy
- Female pts are pregnant/breast feeding, or adults of reproductive potential not employing effective method of birth control. Women of childbearing potential must have negative serum pregnancy test <72 hours prior to administration of Erlotinib
- Co-medication that may interfere w study results
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hyperlipidemia not controlled w medication, psychiatric illness/social situations that would limit compliance w study requirements,/disorders associated w significant immunocompromise
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 |
|---|---|---|
| Erlotinib + sirolimusAlso: sirolimus - Rapamune, erlotinib - Tarceva - OSI-774Erlotinib \& sirolimus on a daily dosing schedule on a 28-day cycle. Dosing was 150 mg of oral erlotinib and 5mg of oral sirolimus for patients not on concurrent CY3PA-inducing anti-epileptics (EIAEDS) and 400 mg of oral erlotinib and 10 mg of oral sirolimus for patients on concurrent EIAEDS. | Drug | Erlotinib + Sirolimus |
Primary outcome
6-month Progression-free Survival (PFS)
Time frame: 6 months
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or death due to any cause. Progression based on Macdonald criteria is defined as a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.
4 secondary outcomes
Median Progression Free Survival (PFS)
Time frame: 2 years
Median Overall Survival (OS)
Time frame: 2 years
Best Radiographic Response
Time frame: 2 years
Number of Participants Experiencing a ≥ Grade 3, Treatment-related, Non-hematologic Toxicity.
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19562254Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Friedman AH, Herndon JE 2nd, Marcello J, Norfleet JA, McLendon RE, Sampson JH, Friedman HS. Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J Neurooncol. 2010 Jan;96(2):219-30. doi: 10.1007/s11060-009-9950-0. Epub 2009 Jun 28.
- The Preston Robert Tisch Brain Tumor Center at DUKELink provided by the sponsor.
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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.
David Reardon, MD principal investigator
Duke Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Erlotinib + sirolimus in people with Glioblastoma and Gliosarcoma, run by Duke University at 1 site 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 13 inclusion and 13 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 7 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
6-month Progression-free Survival (PFS) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00672243, which also lists 1 linked publication.
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 7 Aug 2013.