Gemcitabine Hydrochloride and Docetaxel Followed by Doxorubicin Hydrochloride or Observation in Treating Patients With High-Risk Uterine Leiomyosarcoma Previously Removed by Surgery

PRIMARY OBJECTIVES:

I. To determine whether overall survival of patients with uterus-limited high-grade
leiomyosarcoma is superior among patients assigned to treatment with adjuvant gemcitabine
hydrochloride plus docetaxel followed by doxorubicin hydrochloride compared to patients
assigned to observation.

SECONDARY OBJECTIVES:

I. To determine whether treatment with adjuvant gemcitabine plus docetaxel followed by
doxorubicin improves recurrence-free survival of patients with uterus-limited high-grade
leiomyosarcoma compared to observation.

II. To explore the impact of potential predictors of recurrence or death such as patient age,
institution-reported tumor size, cervix involvement (yes or no), and mitotic rate.
(exploratory)

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive adjuvant gemcitabine hydrochloride IV over 70-90 minutes on days 1
and 8 and docetaxel IV over 30-60 minutes on day 8. Patients also receive filgrastim
subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10. Treatment repeats every
21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Patients then undergo computed tomography (CT) and/or magnetic resonance imaging (MRI).
Patients with no evidence of disease receive doxorubicin hydrochloride IV every 21 days for 4
courses in the absence of disease progression or unacceptable toxicity. Patients also receive
filgrastim SC on days 2-8 or pegfilgrastim SC on day 2 or 3.

Arm II: Patients undergo clinical observation.

After completion of study treatment, patients in both arms are followed up every 4 months for
3 years and then every 6 months for 2 years.

Inclusion Criteria:

- Patients with high-risk uterine leiomyosarcoma (LMS), International 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 (BSO) 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 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/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 (PS) of 0 or 1 OR
Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 OR Karnofsky PS >= 80%

- Patients who have met the pre-entry requirements specified

- Patients must have signed an approved informed consent

- Patients participating through 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 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 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

- 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