Ph II Erlotinib + Sirolimus for Pts w Recurrent Malignant Glioma Multiforme
NCT ID: NCT00672243
Last Updated: 2013-08-07
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
32 participants
INTERVENTIONAL
2007-04-30
2009-12-31
Brief Summary
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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
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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
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Keywords
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Erlotinib + Sirolimus
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.
Erlotinib + sirolimus
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.
Interventions
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Erlotinib + sirolimus
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
Exclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Genentech, Inc.
INDUSTRY
OSI Pharmaceuticals
INDUSTRY
Duke University
OTHER
Responsible Party
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Principal Investigators
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David Reardon, MD
Role: PRINCIPAL_INVESTIGATOR
Duke Health
Locations
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Duke University Health System
Durham, North Carolina, United States
Countries
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References
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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.
Related Links
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The Preston Robert Tisch Brain Tumor Center at DUKE
Other Identifiers
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Pro00000345
Identifier Type: -
Identifier Source: org_study_id