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Phase II Open-Label Trial of Erlotinib (Tarceva) and Bevacizumab in Women With Advanced Ovarian Cancer

Phase 2
18 Years
Not Enrolling
Ovarian Neoplasms

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Trial Information

Phase II Open-Label Trial of Erlotinib (Tarceva) and Bevacizumab in Women With Advanced Ovarian Cancer

Erlotinib and bevacizumab, novel biologics, offer a new regimen for the treatment of ovarian
cancer in women who are refractory to standard drug regimens. Because bevacizumab is an
anti-angiogenesis drug and erlotinib is an EGFR receptor inhibitor their combination would
lead to the inhibition of multiple signal transduction pathways and the reversal of cancer
progression in this difficult to treat population. The study seeks to determine the
efficacy and safety of the EGFR receptor inhibitor, erlotinib plus the anti-angiogenesis
VEGF ligand inhibitor bevacizumab in women with platinum and taxane refractory ovarian

The study design is a non-randomized, open label, single center Phase II trial using a Simon
two stage design. Eligible patients are women who have a histologically or pathologically
confirmed diagnosis of epithelial carcinoma of the ovary or primary peritoneal carcinoma who
have relapsed or are refractory to therapy after primary treatment of their disease.

Patients will be treated with erlotinib 150 mg/day orally and bevacizumab 10mg/kg every two
weeks plus or minus one day intravenously. Forty patients will be enrolled in the study.
Initially 20 eligible patients will be accrued. If one or no confirmed response is
observed, the trial will be closed and the agents considered inactive. Otherwise, 20
additional eligible patients will be accrued for a total of 40 patients. Eight or more
responses out of 40 will be considered evidence warranting further study of the agents
provided other factors, such as progression-free and overall survival, also appear

Previous studies of this combination in non-small cell lung cancer, renal cell carcinoma and
metastatic breast cancer have indicated a potential synergistic effect for these two agents.
Preliminary data for the use of bevacizumab in advanced ovarian cancer indicates that this
agent has single-agent activity. As a result, the researchers are interested in exploring
the role of the combination of erlotinib and bevacizumab in advanced ovarian cancer.

Inclusion Criteria:

- Histologically or pathologically confirmed diagnosis of epithelial carcinoma of the
ovary or primary peritoneal carcinoma.

- Relapsed after prior therapy with taxane and platinum-based therapy, within 6 months
of completing, or had a best response of stable disease during no more than two prior
chemotherapy treatments with a platinum (either cisplatin or carboplatin) and a
taxane (paclitaxel or docetaxel). These agents may have been administered
concurrently or sequentially. Besides the primary chemotherapy, two additional
chemotherapy regimens are allowed. Hormonal therapy is allowed and will not be
counted as a chemotherapy regimen.

- Up to one year of consolidation treatment with intraperitoneal and intravenous
administered chemotherapy drugs to consolidate a clinical complete remission is

- Patients must have elevated CA-125 or measurable disease.

- For patients who do not have RECIST measurable disease, an elevated CA-125 (greater
than two times the institutional upper limit of normal) will be required for

- Debulking surgery for relapsed disease is allowed but must be completed at least 28
days prior to the first day of study therapy. Patient must have recovered from all
side effects of surgery including a completely healed surgical incision.

- Patient must have a Zubrod performance status of 0-1.

- Patient must have adequate hepatic function as defined by:

- a serum bilirubin ≤1.5 x the institutional upper limit of normal (IULN),

- SGOT or SGPT ≤2.5 x the institutional upper limit of normal obtained within 14
days prior to start of therapy

- Patient must have an adequate renal function as defined by:

- a serum creatinine ≤1.5 x the institutional upper limit of normal obtained
within 14 days prior to start of therapy and a urine protein:creatinine (UPC)
ratio of ≤ 1.0.

- Patients must be able to take oral medications

- Patients may not have ongoing problems with bowel obstruction or short bowel syndrome
characterized by grade 2 or greater diarrhea or malabsorptive disorders.

- Patients must have the following hematological criteria:

- Hemoglobin of >10gm/dL,

- White blood cell count >2500,

- Platelets >80,000

- Patients must be ≥ 18 years of age.

Exclusion Criteria:

- Subjects with mixed mullerian tumors and borderline ovarian tumors are excluded.
Patients with a history of borderline ovarian tumors that have evolved into higher
grade tumors will be eligible.

- The patient must not have received chemotherapy, biologic therapy or any other
investigational drug for any reason within 28 days prior to start of therapy and must
have recovered from toxicities of prior therapy to grade 1 or less with the exception
of alopecia.

- Patient must not be pregnant or nursing because bevacizumab or erlotinib maybe
harmful to the developing fetus and newborn. Women of reproductive potential must
have a negative serum pregnancy test within 7 days prior to study consent.
Post-menopausal women must be amenorrheic for at least 12 months to be considered of
non-childbearing potential. Patients of reproductive potential must agree to employ
an effective barrier method of birth control throughout the study and for up to 3
months following discontinuation of study drug.

- Patients should not have psychological, familial, sociological, or geographical
conditions that do not permit medical follow-up or compliance with the study

- Except for cancer-related abnormalities, patients should not have unstable or
preexisting major medical conditions.

- Patients should not have any medical life-threatening complications of their

- Patients should not have a known severe and/or uncontrolled concurrent medical
disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease,
active uncontrolled infection, or HIV)

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study.

- Baseline blood pressure of < or equal to 150/100 mmHg. Patients with a blood pressure
reading above this level should be initiated on anti-hypertensive therapy and may be
considered for protocol treatment when their blood pressure is adequately controlled.

- New York Heart Association (NYHA) Grade II or greater congestive heart failure

- History of myocardial infarction, cerebrovascular accident, transient ischemic
attack, or unstable angina within 6 months

- Clinically significant peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy

- Presence of central nervous system or brain metastases

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, anticipation of need for major surgical procedure during the course
of the study

- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to Day 0

- Pregnant (positive pregnancy test) or lactating

- Urine protein:creatinine ratio > equal to 1.0 at screening

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal

- Serious, non-healing wound, ulcer, or bone fracture

- Diagnosis of any other malignancy except non-melanomatous skin cancer in the past 5

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective Response (Complete Partial, Stable and Progression)

Outcome Description:

Objective response was defined using standard RECIST criteria. CR(complete response)= disappearance of all target lesions PR(partial response)=30% decrease in the sum of the longest diameter of target lesions PD(progressive disease)=20% increase in the sum of the longest diameter of target lesions SD(stable disease)= small changes that do not meet above criteria

Outcome Time Frame:

06.16.2005 to 10.05.2009

Safety Issue:


Principal Investigator

David S Alberts, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Arizona


United States: Institutional Review Board

Study ID:

HSC #05-47;AVF3117s



Start Date:

June 2005

Completion Date:

May 2010

Related Keywords:

  • Ovarian Neoplasms
  • advanced ovarian cancer
  • refractory ovarian cancer
  • primary peritoneal cancer
  • Neoplasms
  • Ovarian Neoplasms



University of Arizona Cancer Center Tucson, Arizona  85724