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

Study ID

Cancer Related

Healthy Volunteers

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital
  • Parkland Health & Hospital System

Annette Paulsen

Principal Investigator
David Miller, M.D.

Official Title

A Phase III Randomized Trial of Gemcitabine (NSC# 613327) Plus Docetaxel (NSC# 628503) Followed by Doxorubicin (NSC# 123127) Versus Observation for Uterus-Limited, High-Grade Uterine Leiomyosarcoma

Brief Overview

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.



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.


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.

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.

Participant Eligibility

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

- 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

- 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

- Patients with gross residual or metastatic tumor findings following complete surgical
treatment for uterine LMS