Bevacizumab and Erlotinib Study in Advanced Ovarian Cancer
Condition: Ovarian Neoplasms
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: bevacizumab; erlotinib
Intervention description: 10mg/kg every two weeks IV-bevacizumab; 150mg daily by mouth-erlotinib
Intervention MeSH terms: Bevacizumab; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: advanced ovarian cancer; refractory ovarian cancer; primary peritoneal cancer

Summary:

      The purpose of this project is to determine if a new combination of drugs, erlotinib
      (Tarceva™) and bevacizumab is safe and effective for treating women diagnosed with ovarian
      cancer whose cancer has progressed while on prior standard chemotherapy treatment with a
      taxane (paclitaxel or docetaxel) and a platinum (cisplatin or carboplatin).
    

Eligibility criteria:

        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
             allowed.

          -  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
             enrollment.

          -  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 protocol.

          -  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
             malignancies

          -  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 abscess

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Diagnosis of any other malignancy except non-melanomatous skin cancer in the past 5
             years.

          -  Inability to comply with study and/or follow-up procedures