Gemcitabine Hydrochloride and Docetaxel Followed by Doxorubicin Hydrochloride or Observation in Treating Patients With High-Risk Uterine Leiomyosarcoma Previously Removed by Surgery
Condition: Stage I Uterine Sarcoma AJCC v7; Uterine Corpus Leiomyosarcoma
MeSH terms: Leiomyosarcoma
Intervention: Clinical Observation; Docetaxel; Doxorubicin Hydrochloride; Filgrastim; Gemcitabine Hydrochloride; Pegfilgrastim
Intervention description: Patients followed clinically; Given IV; Given IV; Given subcutaneously (SC); Given IV; Given SC
Intervention MeSH terms: Gemcitabine; Docetaxel; Doxorubicin; Liposomal doxorubicin; Lenograstim
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies how well gemcitabine hydrochloride and docetaxel
      followed by doxorubicin hydrochloride work compared to observation in treating patients with
      high-risk uterine leiomyosarcoma previously removed by surgery. Drugs used in chemotherapy,
      such as gemcitabine hydrochloride, docetaxel, and doxorubicin hydrochloride, work in
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. It is not yet known whether
      combination therapy after surgery is an effective treatment for uterine leiomyosarcoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with high-risk uterine leiomyosarcoma (LMS), Federation of Gynecology and
             Obstetrics (FIGO) stage I (confined to corpus +/- cervix); patients with known uterine
             serosa involvement are not eligible; patients should have had, at least, a complete
             hysterectomy (including removal of the cervix); bilateral salpingo-oophorectomy is not
             required

               -  Institutional pathology review calls the uterine leiomyosarcoma ?high grade?

               -  Additionally, if the pathology report indicates a mitotic rate, the mitotic rate
                  should be greater than or equal to 5 mitoses/10 high-power field

               -  All patients must be no longer than 12 weeks (3 months) from surgical resection
                  of cancer at the time of enrollment on study; if a patient requires a second
                  operation to complete her surgery, i.e., trachelectomy to remove the cervix
                  and/or bilateral salpingo-oophorectomy (BSO), the 12 weeks may be counted from
                  the time of the second operation

               -  Patients who had a ?morcellation? hysterectomy procedure that involved
                  morcellation within the peritoneal cavity are eligible IF a second operation is
                  performed and biopsies from the second procedure show no evidence of
                  leiomyosarcoma

          -  All patients must have no evidence of persistent or metastatic disease as documented
             by a post-resection computed tomography (CT) of the chest/abdomen/pelvis or by CT
             chest + magnetic resonance imaging (MRI) abdomen/pelvis; the post-resection imaging
             studies should be performed within 4 weeks of registration on study

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL (ANC >= 1.5 x
             10^9/liter [L])

          -  Platelets greater than or equal to 100,000/mcL (platelets >= 100 x 10^9/L)

          -  Hemoglobin greater than 8.0 g/dL (= 80 g/L or 4.9 mmol/L)

          -  Creatinine less than or equal to 1.5 x institutional upper limit of normal (ULN)

          -  Bilirubin* within normal range

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])* and
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT])* less
             than or equal to 2.5 times ULN

          -  Alkaline phosphatase* less than or equal to 2.5 x ULN

          -  * Patients with a history of Gilbert?s syndrome may be eligible provided total
             bilirubin is less than or equal to 1.5 x ULN and the AST, ALT, and alkaline
             phosphatase meet the criteria detailed

          -  Neuropathy (sensory and motor) less than or equal to Common Terminology Criteria for
             Adverse Events (CTCAE) grade 1

          -  Patients with Gynecologic Oncology Group (GOG) performance status of 0 or 1 OR Eastern
             Cooperative Oncology Group (ECOG) PS of 0 or 1 OR Karnofsky performance status (PS) >=
             80%

          -  Patients who have met the pre-entry requirements specified

          -  Patients must have signed an approved informed consent

          -  Patients participating through United States (U.S.) sites must sign an approved and
             authorization permitting release of personal health information

          -  Patients should be free of active infection requiring antibiotics (with the exception
             of an uncomplicated urinary tract infection [UTI])

        Exclusion Criteria:

          -  Patients who have had prior therapy with docetaxel, gemcitabine hydrochloride, or
             doxorubicin hydrochloride at any time in their history

          -  Patients with a history of other invasive malignancies, with the exception of
             non-melanoma skin cancer, are ineligible if there is any evidence of other malignancy
             being present within the last five years; patients are also ineligible if their
             previous cancer treatment contraindicates this protocol therapy

          -  Patients with a history of severe hypersensitivity reaction to Taxotere (docetaxel) or
             other drugs formulated with polysorbate 80

          -  Patients with GOG performance status of 2, 3 or 4; or ECOG performance status of 2, 3
             or 4

          -  Patients who are breast-feeding

          -  Patients with a known history of congestive heart failure or cardiac ejection fraction
             < 50% (or less than institutional normal limits); echocardiogram (ECHO) or multigated
             acquisition scan (MUGA) is not required prior to enrollment; for patients assigned to
             the chemotherapy arm, an ECHO or MUGA should be done within 6 months of day 1 of
             gemcitabine-docetaxel treatment

               -  Patients who enroll on study and are randomized to Regimen I (chemotherapy ) and
                  then are found on baseline ECHO or MUGA to have cardiac ejection fraction < 50%
                  or below institutional normal will remain ON study; such patients will receive
                  gemcitabine + docetaxel for 4 cycles but will NOT receive any doxorubicin
                  treatment; they will continue treatment follow-up as outlined for all patients
                  assigned to Regimen I

          -  Patients with a history of prior whole pelvic radiation

          -  Concurrent treatment with hormone replacement therapy is permitted at the discretion
             of the treating physician; patients who have been taking hormonal/hormone blocking
             agents for breast cancer or breast cancer prevention or other indication are eligible;
             use of anti-hormonal agents (tamoxifen, medroxyprogesterone, aromatase inhibitors) is
             permitted at the discretion of the treating physician; documentation of concurrent
             medications is required

          -  Patients with recurrent uterine LMS

          -  Patients who are known to be human immunodeficiency virus (HIV) positive are not
             eligible

          -  Patients with gross residual or metastatic tumor findings following complete surgical
             treatment for uterine LMS