Ph II Erlotinib + Sirolimus for Pts w Recurrent Malignant Glioma Multiforme

• Status: Completed
• Trial end date: 2009-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborators: Genentech, Inc.; OSI Pharmaceuticals
• Treatments: Erlotinib Hydrochloride; Everolimus; Sirolimus

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