Gemcitabine Hydrochloride and Docetaxel With or Without Bevacizumab in Treating Patients With Advanced or Recurrent Uterine Leiomyosarcoma
Condition: Recurrent Uterine Corpus Sarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma; Uterine Corpus Leiomyosarcoma
MeSH terms: Sarcoma; Leiomyosarcoma; Recurrence
Intervention: Bevacizumab; Docetaxel; Filgrastim; Gemcitabine Hydrochloride; Pegfilgrastim; Placebo
Intervention description: Given IV; Given IV; Given SC; Given IV; Given SC; Given IV
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Gemcitabine; Docetaxel; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim; Immunoglobulin G
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 107.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial is studying gemcitabine hydrochloride, docetaxel, and
      bevacizumab to see how well they work compared with gemcitabine hydrochloride, docetaxel, and
      a placebo in treating patients with advanced or recurrent uterine leiomyosarcoma. Drugs used
      in chemotherapy, such as gemcitabine hydrochloride and docetaxel, work in different ways to
      stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different
      ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
      help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the
      growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether
      gemcitabine hydrochloride and docetaxel are more effective when given with or without
      bevacizumab in treating uterine leiomyosarcoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have advanced or recurrent uterine leiomyosarcoma with documented
             disease progression; histologic confirmation of the original primary tumor is required

          -  All patients must have measurable disease as defined by RECIST 1.1; measurable disease
             is defined as at least one lesion that can be accurately measured in at least one
             dimension (longest diameter to be recorded); each lesion must be >= 10 mm when
             measured by CT, MRI or caliper measurement by clinical exam; or >= 20 mm when measured
             by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

          -  Patient must have at least one "target lesion" to be used to assess response on this
             protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be
             designated as "non-target" lesions unless progression is documented or a biopsy is
             obtained to confirm persistence at least 90 days following completion of radiation
             therapy

          -  Patients must have a GOG Performance Status of 0, 1, or 2

          -  Patients must have recovered from effects of recent surgery, radiotherapy or other
             therapy

          -  Patients should be free of active infection requiring antibiotics (with the exception
             of an uncomplicated UTI)

          -  Any hormonal therapy directed at the malignant tumor must be discontinued at least one
             week prior to first day of study treatment; continuation of hormone replacement
             therapy is permitted

          -  Platelet count greater than or equal to 100,000/mm^3

          -  ANC count greater than or equal to 1,500/mm^3

          -  Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), per NCI
             CTCAE Version 4.0 Grade 1

          -  Bilirubin within normal range (CTCAE Version 4 Grade 0)

          -  SGOT and alkaline phosphatase less than or equal to 2.5 x ULN, per the CTCAE Version
             4.0 Grade 1)

          -  SGOT less than or equal to 2.5 x ULN, per the CTCAE Version 4.0 Grade 1

          -  Alkaline phosphatase less than or equal to 2.5 x ULN, per the CTCAE Version 4.0 Grade
             1

          -  Neuropathy (sensory and motor) less than or equal to Grade 1 per the CTCAE Version
             4.0.

          -  No history of transient ischemic attack (TIA) or stroke or CNS hemorrhage within the
             past 6 months

          -  Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection
             of 24-hour urine measurement of urine protein is recommended

          -  PT such that international normalized ratio (INR) is =< 1.5 and a PTT =< 1.5 times the
             institutional upper limit of normal (or an in-therapeutic-range INR, usually between 2
             and 3, if a patient is on a stable dose of therapeutic warfarin)

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal health information

          -  Patients must meet pre-entry requirements

          -  Patients of childbearing potential must have a negative serum pregnancy test prior to
             the study entry and be practicing an effective form of contraception

        Exclusion Criteria:

          -  Patients who have received prior cytotoxic chemotherapy for management of uterine
             sarcoma; patients who have received prior VEGF-pathway targeted agent such as
             bevacizumab, PTK787, VEGF-trap, or who have received prior treatment with a
             multi-kinase inhibitor such as sorafenib or sunitinib are not eligible

          -  Patients who have had prior therapy with docetaxel or gemcitabine or bevacizumab

          -  Patients with a history of other invasive malignancies, with the exceptions of
             non-melanoma skin cancer, carcinoma in situ of the cervix, and ductal carcinoma in
             situ of the breast, are excluded if there is any evidence of other malignancy being
             present within the last five years; patients are also excluded if their previous
             cancer treatment contraindicates this protocol therapy

          -  Patients with active bleeding or pathologic conditions that carry high risk of
             bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
             vessels; (necessary use of warfarin or low molecular weight heparin is permitted,
             provided the INR is maintained in the therapeutic range of approximately 2-3)

          -  Patients with major surgery or significant traumatic injury within 28 days prior to
             study entry

          -  Patients with a history of abdominal fistula or perforation within the past 12 months

          -  Patients with a current, serious, non-healing wound, ulcer, or bone fracture

          -  Patients with history or evidence upon physical examination of CNS disease, including
             history of primary brain tumor, or any history of brain metastases, or seizures not
             controlled with standard medical therapy

          -  Patients with known hypersensitivity to Chinese hamster ovary cell products or other
             recombinant human or humanized antibodies

          -  Cardiovascular function; specifically, patient may not have:

               -  Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 100 mm
                  Hg in a patient with no history of hypertension; patients with a history of
                  hypertension before enrollment on study are permitted, but such patients must
                  have BP less than or equal to 140/90 mmHg; use of blood pressure medications to
                  achieve and maintain blood pressure control is permitted

               -  Myocardial infarction or unstable angina within 6 months of the first date of
                  bevacizumab/placebo therapy

               -  New York Heart Association (NYHA) Grade II or greater congestive heart failure or
                  serious cardiac arrhythmia requiring medication; women who have received prior
                  treatment with an anthracycline (including doxorubicin and/or liposomal
                  doxorubicin) and have an ejection fraction < 50% will be excluded from the study

               -  Grade 1, Category 2 or greater, peripheral vascular disease; patient cannot have
                  anything worse than mild, symptomatic claudication with exercise

               -  History of cerebrovascular accident (CVA, stroke), transient ischemic attack
                  (TIA) or subarachnoid hemorrhage within six months of the first date of
                  bevacizumab/placebo therapy

               -  History of pulmonary embolism or deep vein thrombosis in the past 6 months

          -  Patients with, or with anticipation of, invasive procedures as defined below:

               -  Major surgical procedure, open biopsy or significant traumatic injury within 28
                  days prior to the first date of bevacizumab/placebo therapy

               -  Major surgical procedure anticipated during the course of the study.

               -  Minor surgical procedures (i.e., mediport insertion), fine needle aspirates, or
                  core biopsies within 7 days prior to the first date of bevacizumab/placebo
                  therapy

          -  Patients who are pregnant or nursing