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Sorafenib and Erlotinib in Treating Patients With Metastatic or Unresectable Solid Tumors

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: NCT00126620
Recruitment Status : Completed
First Posted : August 4, 2005
Last Update Posted : July 23, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:

RATIONALE: Sorafenib and erlotinib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib and erlotinib in treating patients with metastatic or unresectable solid tumors.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: erlotinib hydrochloride Drug: sorafenib tosylate Phase 1

Detailed Description:



  • Determine the maximum tolerated dose and recommended phase II dose of sorafenib and erlotinib in patients with metastatic or unresectable solid tumors.


  • Determine the optimal biologically effective dose of this regimen that will lead to hypophosphorylation of epidermal growth factor receptor (EGFR), ERK, Akt, and vascular endothelial growth factor receptor (VEGFR), and inhibition of angiogenesis and apoptosis with tolerable toxicity in these patients.
  • Correlate the pharmacokinetic profiles of this regimen with toxicity and biological activity in these patients.
  • Determine, preliminarily, the antitumor activity of this regimen in these patients.
  • Correlate phosphorylation status of EGFR, ERK, Akt, and VEGFR with antitumor activity of this regimen in these patients.

OUTLINE: This is a multicenter, open label, non-randomized, dose-escalation study.

Patients receive oral sorafenib alone once or twice daily on days -6 to 0*. Patients then receive oral sorafenib once or twice daily and oral erlotinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Not considered part of course 1; considered a "run-in" period only.

Cohorts of 3-6 patients receive escalating doses of sorafenib and erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD.

After completion of study treatment, patients are followed at 4 weeks and then at least annually thereafter.

PROJECTED ACCRUAL: A total of 16-28 patients will be accrued for this study within 5-14 months.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib; Tarceva) in Advanced Solid Tumors
Study Start Date : September 2005
Actual Primary Completion Date : May 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: OSI-774 erlotinib) and Bay 43-9006 (Sorafenib)
Sorafenib administered alone for a 1-week run-in period, and then both drugs e given together continuously, with every 28 days considered as a cycle. Three dose levels assessed.
Drug: erlotinib hydrochloride
Drug: sorafenib tosylate

Primary Outcome Measures :
  1. Maximum tolerated dose and recommended phase II dose [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. Pharmacodynamic outcomes [ Time Frame: Pre study and cycle 1 ]
  2. Pharmacokinetic outcomes [ Time Frame: Pre-study, cycle 1 and cycle 2 ]
  3. Antitumor activity [ Time Frame: Every 8 wks ]
  4. Correlation of EGFR, AKT, ERK and VEGFR with antitumor activity [ Time Frame: If responses or prolonged stable disease are observed ]
  5. EGFR activating mutations, gene amplification status, EGFR intron 1 polymorphism if responses or prolonged disease stabilization are seen [ Time Frame: If responses or prolonged stable disease are observed ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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


  • Histologically confirmed solid tumor

    • Metastatic or unresectable disease
  • Standard curative or palliative measures do not exist OR are no longer effective
  • Measurable disease by radiography (for patients treated at the maximum tolerated dose [MTD] only)
  • Tumor accessible for serial biopsies (for patients treated at the MTD only)
  • No known brain metastases



  • 18 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • More than 12 weeks


  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • No bleeding diathesis or coagulopathy


  • Bilirubin normal
  • AST and ALT ≤ 2.5 times ULN
  • PT INR ≤ 1.5 unless on full-dose warfarin


  • Creatinine normal OR
  • Creatinine clearance ≥ 60 mL/min


  • No uncontrolled hypertension (i.e., systolic blood pressure [BP] > 140 mm Hg or diastolic BP > 90 mm Hg despite medication)
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia


  • No abnormalities of the cornea, including any of the following:

    • Dry eye syndrome
    • Sjögren's syndrome
    • Congenital abnormalities (e.g., Fuch's dystrophy)
    • Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
    • Abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)


  • No active peptic ulcer disease that would impair the ability to swallow pills
  • No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Willing to undergo serial biopsies, positron emission tomography, and CT scanning (for patients treated at the MTD only)
  • No ongoing or active infection
  • No significant traumatic injury within the past 3 weeks
  • No history of allergic reaction to drugs of similar chemical or biological composition to study drugs
  • No psychiatric illness or social situation that would preclude study compliance
  • No other condition that would impair the ability to swallow pills
  • No other uncontrolled illness


Biologic therapy

  • No concurrent prophylactic hematopoietic colony-stimulating factors


  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

  • Not specified


  • More than 4 weeks since prior radiotherapy (except for low dose, non-myelosuppressive radiotherapy) and recovered


  • More than 3 weeks since prior major surgery
  • No prior surgical procedure affecting absorption


  • No prior sorafenib or erlotinib
  • No other prior agents targeting Raf, vascular endothelial growth factor (VEGF), VEGF receptor, or epidermal growth factor receptor
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
  • No concurrent CYP3A4 inducers (e.g., rifampin or Hypericum perforatum [St. John's wort])
  • No other concurrent anticancer therapy
  • Concurrent prophylactic anticoagulation therapy (e.g., low-dose warfarin) allowed provided PT INR < 1.1 times upper limit of normal (ULN)
  • Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided both of the following criteria are met:

    • Patient has an in range INR (between 2-3) while on a stable-dose of oral anti-coagulant OR a stable-dose of low molecular weight heparin
    • No active bleeding OR pathological condition that would confer a high risk of bleeding (e.g., tumor involving a major vessel 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): NCT00126620

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Canada, Ontario
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
National Cancer Institute (NCI)
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Study Chair: Lillian L. Siu, MD, FRCPC Princess Margaret Hospital, Canada
Publications of Results:
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Responsible Party: University Health Network, Toronto Identifier: NCT00126620    
Other Study ID Numbers: PMH-PHL-042
CDR0000437855 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: August 4, 2005    Key Record Dates
Last Update Posted: July 23, 2015
Last Verified: July 2015
Keywords provided by University Health Network, Toronto:
unspecified adult solid tumor, protocol specific
Additional relevant MeSH terms:
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Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action