Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00335764
Recruitment Status : Completed
First Posted : June 12, 2006
Last Update Posted : December 29, 2016
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase I/II trial is studying the side effects and best dose of erlotinib, tipifarnib, and temsirolimus when given together with sorafenib and to see how well they work in treating patients with recurrent glioblastoma multiforme or gliosarcoma. Sorafenib, erlotinib, tipifarnib, and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib and tipifarnib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with erlotinib, tipifarnib, or temsirolimus may kill more tumor cells.

Condition or disease Intervention/treatment Phase
Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor Drug: sorafenib tosylate Drug: erlotinib hydrochloride Drug: tipifarnib Drug: temsirolimus Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Studies of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib), R115777 (Tipifarnib) or CCI-779 (Temsirolimus) in Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
Study Start Date : April 2006
Actual Primary Completion Date : February 2010
Actual Study Completion Date : September 2012

Arm Intervention/treatment
Experimental: Group 1
Patients receive oral sorafenib tosylate twice daily and oral erlotinib hydrochloride once daily on days 1-28.
Drug: sorafenib tosylate
given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN

Drug: erlotinib hydrochloride
given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774

Experimental: Group 2
Patients receive sorafenib tosylate as in group 1. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
Drug: sorafenib tosylate
given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN

Drug: temsirolimus
IV administration
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel

Experimental: Group 3
Patients receive sorafenib tosylate as in group 1. Patients also receive oral tipifarnib twice daily on days 1-21.
Drug: sorafenib tosylate
given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN

Drug: tipifarnib
given orally
Other Names:
  • R115777
  • Zarnestra

Primary Outcome Measures :
  1. Maximally tolerated dose of the each combination agent combined with a fixed dose of BAY 43-9006 determined by dose-limiting toxicities (Phase I) [ Time Frame: 28 days ]
  2. Progression-free survival (Phase II) [ Time Frame: 6 months ]
    Distributions will be estimated using Kaplan-Meier method.

Secondary Outcome Measures :
  1. Objective response rate (CR, PR, SD, PD) in patients with measurable disease (Phase II) [ Time Frame: Up to 5 years ]
    The proportion of patients in each of the four response categories (CR, PR, SD, PD) will be computed and point estimates and confidence intervals will be provided.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed intracranial glioblastoma multiforme or gliosarcoma
  • Evidence of tumor progression by MRI or CT scan within the past 14 days AND on a steroid dose that has been stable for ≥ 5 days
  • Patients who underwent prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis by either positron emission tomography or thallium scanning, MR spectroscopy, or surgical documentation of disease
  • Recent resection of recurrent or progressive tumor allowed
  • Residual disease is not required
  • Treatment for any number of prior relapses, defined as disease progression after initial therapy (i.e., radiotherapy with or without chemotherapy if used as initial treatment), allowed (phase I)
  • No more than 3 prior therapies (initial therapy and therapy for 2 relapses) (phase II)
  • Each of the following is considered 1 relapse:

    • Disease progression after initial therapy (i.e., radiotherapy with or without chemotherapy if used as initial therapy)
    • Underwent a surgical resection for relapsed disease and received no anticancer therapy for up to 12 weeks after surgical resection AND then underwent a subsequent surgical resection
    • Received prior therapy for a low-grade glioma, followed by a surgical diagnosis of glioblastoma
    • Failed prior radiotherapy
  • 15 unstained paraffin slides or 1 tissue block must be available from original surgery, definitive surgery, or surgery closest to the initiation of this study (phase II)
  • Karnofsky performance status 60-100%
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)
  • AST/ALT ≤ 2.5 times upper limit of normal (ULN)
  • Total bilirubin normal
  • Creatinine < 1.5 mg/dL
  • PT/INR ≤ 1.5 (INR < 3.0 for patients on anticoagulation therapy)
  • INR < 1.1 times ULN (for patients on prophylactic anticoagulation therapy [low-dose warfarin])
  • Fasting cholesterol < 350 mg/dL (for patients receiving temsirolimus and sorafenib)
  • Fasting triglycerides < 400 mg/dL (for patients receiving temsirolimus and sorafenib)
  • Well-controlled hypertension (e.g., systolic blood pressure ≤ 140 mm Hg or diastolic pressure ≤ 90 mm Hg) allowed
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for at least 2 weeks (women) or 3 months (men) after completion of study treatment
  • No peripheral neuropathy > grade 1 (for patients receiving sorafenib and tipifarnib)
  • No evidence of bleeding diathesis or coagulopathy
  • No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for ≥ 3 years
  • No significant traumatic injury within the past 21 days
  • No active infection or serious medical illness that would preclude study treatment
  • No condition that would impair ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation or active peptic ulcer disease)
  • No HIV disease
  • No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole or econazole) or a history of allergic reactions attributed to any compound of similar chemical or biological composition to tipifarnib (for patients receiving sorafenib and tipifarnib)
  • No other disease that would obscure toxicity or dangerously alter drug metabolism
  • Recovered from prior therapy
  • At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin) (radiosensitizer does not count)
  • At least 14 days since prior vincristine
  • At least 21 days since prior procarbazine or major surgery
  • At least 28 days since prior investigational agent or cytotoxic therapy
  • At least 42 days since prior nitrosoureas or radiotherapy
  • No prior sorafenib, AEE788, or vatalanib
  • No prior surgical procedures affecting absorption
  • No prior tipifarnib, lonafarnib, or other agents targeting farnesyl transferase (for patients receiving sorafenib and tipifarnib)
  • No prior temsirolimus or mTOR-targeting agent (phase II), rapamycin or everolimus, or Akt-pathway inhibitors (for patients receiving sorafenib and temsirolimus)
  • No prior erlotinib hydrochloride, AEE788, or other epidermal growth factor receptor targeting agents (phase II) (for patients receiving sorafenib and erlotinib hydrochloride)
  • No concurrent enzyme-inducing antiepileptic drugs (e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital, or primidone)
  • Dexamethasone allowed
  • No concurrent hepatic cytochrome p450 enzyme-inducing anticonvulsants
  • No other concurrent investigational agents or anticancer therapies, including chemotherapy, radiotherapy, hormonal therapy, or immunotherapy
  • No concurrent prophylactic filgrastim (G-CSF) or other hematopoietic colony-stimulating factors
  • Full-dose anticoagulants allowed provided both of the following criteria are met:

    • In-range INR (between 2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
    • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00335764

United States, California
University of California at Los Angeles
Los Angeles, California, United States, 90095
University of California San Francisco
San Francisco, California, United States, 94115
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Mark Gilbert, MD National Cancer Institute (NCI)

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00335764     History of Changes
Other Study ID Numbers: NCI-2009-00676
NCI-2009-00676 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NABTC-05-02 ( Other Identifier: Adult Brain Tumor Consortium )
NABTC-05-02 ( Other Identifier: CTEP )
U01CA137443 ( U.S. NIH Grant/Contract )
First Posted: June 12, 2006    Key Record Dates
Last Update Posted: December 29, 2016
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents