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

NCT00672243 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00000345
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioblastoma; Gliosarcoma

Keywords

GBM; Brain tumor; Erlotinib; Sirolimus; Glioblastoma multiforme; Glioblastoma; Gliosarcoma3; Tarceva; Rapamune

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (4)

• Median Progression Free Survival (PFS)

  2 years

• Median Overall Survival (OS)

  2 years

• Best Radiographic Response

  2 years

• Number of Participants Experiencing a ≥ Grade 3, Treatment-related, Non-hematologic Toxicity.

  2 years

Study Arms (1)

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.

Drug: Erlotinib + sirolimus

Interventions

Erlotinib + sirolimus DRUG

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.

Also known as: sirolimus - Rapamune, erlotinib - Tarceva - OSI-774

Erlotinib + Sirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Genentech, Inc.: collaborator
• OSI Pharmaceuticals: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 19562254 RESULT

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Erlotinib Hydrochloride; Sirolimus

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: David A. Reardon, MD
• Organization: The Preston Robert Tisch Brain Tumor Center at Duke

reard003@mc.duke.edu

(919) 668-1409

Study Officials

• David Reardon, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: May 6, 2008
• Study Start: April 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: December 1, 2009
• Last Updated: August 7, 2013
• Results First Posted: April 4, 2013

Record last verified: 2013-07

Locations

US (1)