Ph II Erlotinib + Sirolimus for Pts w Recurrent Malignant Glioma Multiforme
Condition: Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Glioma; Gliosarcoma
Intervention: Erlotinib + sirolimus
Intervention description: 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.
Intervention MeSH terms: Sirolimus; Erlotinib Hydrochloride; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GBM; Brain tumor; Erlotinib; Sirolimus; Glioblastoma multiforme; Glioblastoma; Gliosarcoma3; Tarceva; Rapamune

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 evaluate progression free survival, radiographic
      response and overall survival of patients with recurrent GBM treated with Erlotinib plus
      Sirolimus.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

          -  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 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

          -  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