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A Phase I Study of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib; Tarceva) in Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib; Tarceva) in Advanced Solid Tumors



- 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

Inclusion Criteria


- 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

- 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

- No concurrent CYP3A4 inducers (e.g., rifampin or Hypericum perforatum [St. John's

- 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)

Type of Study:


Study Design:

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose and recommended phase II dose

Safety Issue:


Principal Investigator

Lillian L. Siu, MD, FRCPC

Investigator Role:

Study Chair

Investigator Affiliation:

Princess Margaret Hospital, Canada


United States: Federal Government

Study ID:




Start Date:

September 2005

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms