Erlotinib and Sorafenib in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
Condition: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor
MeSH terms: Glioblastoma; Gliosarcoma; Recurrence
Intervention: erlotinib hydrochloride; sorafenib tosylate; pharmacological study
Intervention description: 150mg Given orally once daily; 400mg Given orally twice daily; Correlative studies
Intervention MeSH terms: Erlotinib Hydrochloride; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving erlotinib together with sorafenib works in
      treating patients with progressive or recurrent glioblastoma multiforme. Erlotinib and
      sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth and by blocking blood flow to the tumor. Giving erlotinib together with sorafenib may
      kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed supratentorial glioblastoma multiforme
             which is progressive or recurrent after radiation therapy ± chemotherapy; patients
             with previous low grade glioma who progressed after radiotherapy ± chemotherapy and
             are biopsied and found to have a high grade glioma are eligible

          -  Patients must have tissue specimens available and agree to have their blood and tissue
             blocks (or slides) submitted for the combined correlative studies

          -  Patients must have measurable contrast enhancing progressive or recurrent glioblastoma
             multiforme by MRI or CT imaging (Within 14 days before starting treatment)

          -  Patients must have recovered from toxicity of prior therapy. An interval of at least 3
             months must have elapsed since the completion of the most recent course of radiation
             therapy, while at least 3 weeks must have elapsed since the completion of a
             non-nitrosourea containing chemotherapy regimen, and at least 6 weeks since the
             completion of a nitrosourea containing chemotherapy regimen; NOTE: For a
             non-cytotoxic, FDA approved agents (i.e. Celebrex, thalidomide, etc.) therapy could be
             started 2 weeks after discontinuing this agent provided the patient has fully
             recovered from all toxicity associated with the agent; for investigational,
             non-cytotoxic agents a minimum of 3 weeks must have elapsed before the patient will be
             eligible for this study

          -  Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be
             able to care for himself/herself with occasional help from others)

          -  Absolute Neutrophil Count >= 1500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Creatinine =< 1.7mg/dl

          -  Total Bilirubin within normal institutional limits

          -  Transaminases =< 2.5 times above the upper limits of the institutional norm

          -  PT, PTT ≤ institutional norm

          -  Patients must be able to provide written informed consent

          -  Patients with the potential for pregnancy or impregnating their partner must agree to
             follow acceptable birth control methods to avoid conception; women of childbearing
             potential must have a negative serum pregnancy test; (the anti-proliferative activity
             of this experimental drug may be harmful to the developing fetus or nursing infant)

          -  Patients must have a Mini Mental State Exam score >= 15

        Exclusion Criteria:

          -  Patients with serious concurrent infection or medical illness which would jeopardize
             the ability of the patient to receive the treatment outlined in this protocol with
             reasonable safety; (examples of medical illnesses are [but not limited to] the
             following: uncontrolled hypertension, symptomatic congestive heart failure, unstable
             angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that
             would limit compliance with study requirements)

          -  Patients with uncontrolled hypertension; hypertension with systolic blood pressure of
             > 140 mmHg or diastolic pressure > 90 mmHg; however, patients with well-controlled
             hypertension are eligible

          -  Patients who are pregnant or breast-feeding (the anti-proliferative activity of this
             experimental drug may be harmful to the developing fetus or nursing infant)

          -  Patients who have received more than two prior treatments

          -  Patients who have had prior therapy with erlotinib or sorafenib or any other agent
             targeting EGFR

          -  Patients receiving concurrent therapy for their tumor (with the exception of steroids)

          -  Patients undergoing major surgery or sustaining a significant traumatic injury within
             21 days prior to treatment are ineligible

          -  Patients with a concurrent malignancy are ineligible unless they are patients with
             curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients
             with a prior malignancy are ineligible unless they have been free of disease for >=
             five years

          -  Patients must not have any evidence of bleeding diathesis or coagulopathy

          -  Patients with PT INR > 1.5 are excluded, unless the patient is on full dose warfarin

          -  Patients on full-dose anticoagulants (e.g., warfarin) are eligible provided that both
             of the following criteria are met:

               -  The patient has an in-range INR (usually between 2 and 3) on a stable dose of
                  oral anticoagulant or on a stable dose of low molecular weight heparin

               -  The patient has no active bleeding or pathological condition that carries a high
                  risk of bleeding (e.g., tumor involving major vessels or known varices)

               -  NOTE: Patients on a full dose of anticoagulants will a different schedule for
                  PT/INR evaluations

          -  Prophylactic anticoagulation (i.e. low dose warfarin) are eligible provided their
             coagulation parameter levels are as follows: prothrombin time (INR; International
             Normalized Ratio of prothrombin time) < 1.1 x institutional upper limit of normal

          -  Patients with known abnormalities of the cornea based on history (e.g., dry eye
             syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy),
             abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose),
             and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production
             test) are excluded

          -  Patients with any condition (e.g., gastrointestinal tract disease resulting in an
             inability to take oral medication or a requirement for IV alimentation, prior surgical
             procedures affecting absorption, or active peptic ulcer disease) that impairs their
             ability to swallow pills are excluded

          -  Patients cannot be receiving cytochrome P450-inducing anticonvulsants (EIAEDs; e.g.,
             phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) and must not have
             taken them for at least 10 days

          -  Patients may not have allergies to or a history of allergic reactions attributed to
             erlotinib and/or sorafenib

          -  Eligibility of patients receiving any other medications or substances known to affect
             or with the potential to affect the activity or pharmacokinetics of erlotinib or
             sorafenib will be determined following review of their case by the Principal
             Investigator

          -  HIV patients receiving combination anti-retroviral therapy will be excluded