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A Phase II Trial of Tarceva (Erlotinib) and Avastin (Bevacizumab) in the Treatment of Patients With Metastatic Melanoma

Phase 2
18 Years
Not Enrolling

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Trial Information

A Phase II Trial of Tarceva (Erlotinib) and Avastin (Bevacizumab) in the Treatment of Patients With Metastatic Melanoma



- Determine the overall response rate, response duration, and frequency of
progression-free survival at 6 months in patients with stage IV melanoma treated with
erlotinib hydrochloride and bevacizumab.

- Determine objective responses in patients treated with this regimen.


- Determine the overall safety and tolerability of this regimen in these patients.

- Evaluate tissue blocks for EGFR by monoclonal antibody H11 (DAKO) or fluorescence in
situ hybridization(FISH)7p12-specific probe-overexpression or amplification in patients
treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily on days 1-28 and bevacizumab IV
over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of
disease progression or unacceptable toxicity.

Patients undergo tissue collection to analyze EGFR by monoclonal antibody H11 (DAKO) or
fluorescence in situ hybridization (FISH) 7p12-specific probe-overexpression or
amplification. Biological markers AKT, MAPK, p27, p21, CD13, CD34, and factor VIII are also

After completion of study treatment, patients are followed periodically.

Inclusion Criteria:

- Measurable Stage IV melanoma

- Easter Cooperative Oncology Group (ECOG) Performance Status must be 0-1

- Good organ function as demonstrated by, Creatinine <, AST or ALT <5 times
upper limit of normal for subjects with documented liver metastases; <2.5 times the
upper limit of normal (ULN) for subjects without evidence of liver metastases,
bilirubin<2.0mg/dl,, absolute neutrophil count (ANC)>1500/ul, platelets>75k/ul,
hemoglobin (Hgb)>9 (may be transfused to obtain)

- Prior therapy: adjuvant interferon (IFN) allowed; no more than one prior regimen for
advanced stage IV disease

- Patients must have a life expectancy of >3 months

- Patients with brain metastases are eligible only if they fulfill the following:
resected or stereotactic treatment a minimum of 3 months previously and no active CNS
disease since then; brain metastases treated greater than 6 months ago without
evidence of progression or hemorrhage, <1cm in size per lesion (up to 3 lesions), and
off all steroids

- Patients may not have received other agents, either investigational or marketed,
which act by either EGFr inhibition or anti-angiogenesis mechanisms. Other epidermal
growth factor receptor (EGFR) inhibitors include (but are not limited to): Iressa,
erbitux, CI-1033. Angiogenesis inhibitors include (but are not limited to): SU5416,
SU6668, SU 0122348, CP547632, VEGF Trap, anti-integrin αVβ3.

- Recovered from toxicity of major surgery (4 wks), chemotherapy or biologic therapy (4
wks), and/or radiation therapy (2 wks)

- No active other malignancy within 12 months

- No active systemic infection

- Over age of 18 years and signed IRB approved informed consent

Exclusion Criteria:

- Subjects meeting any of the following criteria (3.2.2—3.2.16) are ineligible for
study entry

- Compromised renal or hepatic function as defined by Creatinine >2.0mg/dl, aspartate
transaminase (AST) or alanine transaminase (ALT) >5 times upper limit of normal for
subjects with documented liver metastases; >2.5 times the upper limit of normal (ULN)
for subjects without evidence of liver metastases

- Patient may not be part of any other investigational studies

- internationalized normal ratio (INR) > 1.5

- Patients with PEG or G-tube are ineligible.

- Major surgical procedure, open biopsy; or significant traumatic injury within 28
days, or anticipation of need for major surgical procedure during the course of the

- Any non-healing wound, ulcer, or bone fracture.

- Any clinical evidence or history of a bleeding diathesis or coagulopathy.

- Patients with a history of deep vein thrombosis or thromboembolic disease within the
past 6 months.

- History of acute myocardial infarction within 6 months. In addition, patients are
ineligible if they have clinically significant cardiovascular disease ((e.g.,
uncontrolled hypertension [blood pressure of >160/110 mmHg on medication], New York
Heart Association (NYHA) Grade II or greater congestive heart failure, serious
cardiac dysrhythmia requiring medication, or peripheral vascular disease (Grade II or

- Patients with > 1+ proteinuria will have 24-hour urine collection; for protein.
Patients with ≥ 1gm protein/24 hrs will be excluded

- If child bearing age must not be pregnant or nursing and use methods to prevent

- History or evidence upon physical examination of central nervous system (CNS) disease
(e.g., primary brain tumor, seizures not controlled with standard medical therapy, or
history of stroke)

- Inability to comply with study and/or follow-up procedures

- History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that might affect the
interpretation of the results of the study or render the subject at high risk from
treatment complications.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients With Response

Outcome Description:

Per Response Evaluation Criteria in Solid Tumor (RECIST): Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.

Outcome Time Frame:

At 6 months

Safety Issue:


Principal Investigator

Jeffrey A. Sosman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2004

Completion Date:

September 2008

Related Keywords:

  • Melanoma
  • stage IV melanoma
  • recurrent melanoma
  • Melanoma



Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Sarah Cannon Research Institute Nashville, Tennessee  37203
Vanderbilt-Ingram Cancer Center - Cool Springs Nashville, Tennessee  37064
Vanderbilt-Ingram Cancer Center at Franklin Nashville, Tennessee  37064