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Sorafenib Combined With Erlotinib, Tipifarnib, or Temsirolimus in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
This study is ongoing, but not recruiting participants.

First Received on June 8, 2006.   Last Updated on June 27, 2011   History of Changes
Sponsor: Sidney Kimmel Comprehensive Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00335764
  Purpose

RATIONALE: 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.

PURPOSE: 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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: erlotinib hydrochloride
Drug: sorafenib tosylate
Drug: temsirolimus
Drug: tipifarnib
Phase I
Phase II

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (Phase I) [ Time Frame: continous ] [ Designated as safety issue: Yes ]
  • Progression-free survival (PFS) at 6 months (Phase II) [ Time Frame: continous ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate (Phase II) [ Time Frame: continous ] [ Designated as safety issue: No ]
  • Median PFS (Phase II) [ Time Frame: continous ] [ Designated as safety issue: No ]
  • Toxicity (Phase II) [ Time Frame: continous ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (Phase II) [ Time Frame: continous ] [ Designated as safety issue: No ]

Estimated Enrollment: 183
Study Start Date: April 2006
Estimated Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Patients receive oral sorafenib twice daily and oral erlotinib hydrochloride once daily on days 1-28.
Drug: erlotinib hydrochloride
Given orally
Drug: sorafenib tosylate
Given orally
Experimental: Group 2
Patients receive sorafenib as in group 1. Patients also receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22.
Drug: sorafenib tosylate
Given orally
Drug: temsirolimus
Given IV
Experimental: Group 3
Patients receive sorafenib as in group 1. Patients also receive oral tipifarnib twice daily on days 1-21.
Drug: sorafenib tosylate
Given orally
Drug: tipifarnib
Given orally

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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)

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • 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)
  • No other concurrent CYP3A4 inducers (e.g., rifampin or Hypericum perforatum [St. John's wort])

    • 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00335764

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at 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, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-6220
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Mark R. Gilbert, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
Prados M, Gilbert M, Kuhn J, et al.: Phase I/II study of sorefenib and erlotinib for patients with recurrent glioblastoma (GBM) (NABTC 05-02). [Abstract] J Clin Oncol 27 (Suppl 15): A-2005, 2009.
Wen PY, Cloughesy T, Kuhn J, et al.: Phase I/II study of sorafenib and temsirolimus for patients with recurrent glioblastoma (GBM) (NABTC 05-02). [Abstract] J Clin Oncol 27 (Suppl 15): A-2006, 2009.

Responsible Party: Director, ABTC, Adult Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT00335764     History of Changes
Other Study ID Numbers: CDR0000476286, U01CA062399, ABTC-05-02, NABTC-05-02
Study First Received: June 8, 2006
Last Updated: June 27, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
recurrent adult brain tumor

Additional relevant MeSH terms:
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Sirolimus
Everolimus
Tipifarnib
Sorafenib
Erlotinib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on February 09, 2012