Gemcitabine Hydrochloride and Docetaxel With or Without Bevacizumab in Treating Patients With Advanced or Recurrent Uterine Leiomyosarcoma

A Randomized Phase III Evaluation of Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF With Bevacizumab (NSC #704865) Versus Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF With Placebo in the Treatment of Recurrent or Advanced Leiomyosarcoma of the Uterus

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.

Study Overview

• Status: Terminated
• Conditions: Recurrent Uterine Corpus Sarcoma; Uterine Corpus Leiomyosarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma
• Intervention / Treatment: Drug: Docetaxel; Drug: Gemcitabine Hydrochloride; Biological: Pegfilgrastim; Biological: Filgrastim; Biological: Bevacizumab; Other: Placebo

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether the addition of bevacizumab to fixed-dose rate gemcitabine-docetaxel reduces the progression-free survival (PFS) event rate when compared to gemcitabine-docetaxel plus placebo in patients with advanced or recurrent uterine leiomyosarcoma (LMS).

SECONDARY OBJECTIVES:

I. To determine the objective response rate, as measured by RECIST, of patients treated with fixed-dose rate gemcitabine-docetaxel with bevacizumab, compared with the objective response rate of patients treated with fixed-dose rate gemcitabine-docetaxel with placebo.

II. To determine if the addition of bevacizumab to the combination of gemcitabine and docetaxel increases overall survival in patients with advanced or recurrent uterine LMS.

III. To determine the toxicity profile of fixed-dose rate gemcitabine-docetaxel with and without bevacizumab in this patient population.

IV. To bank formalin-fixed and paraffin-embedded (FFPE) tumor tissue for research.

OUTLINE: This is a multicenter study. Patients are stratified according to prior whole-pelvic radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10.

ARM II: Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Saint Joseph's Hospital and Medical Center
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Concord, California, United States, 94520
      • John Muir Medical Center-Concord Campus
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles County-USC Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA / Jonsson Comprehensive Cancer Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Gynecologic Oncology
    • Orange, California, United States, 92868
      • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • San Diego, California, United States, 92103
      • University of California San Diego
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • Sylmar, California, United States, 91342
      • Olive View-University of California Los Angeles Medical Center
    • Walnut Creek, California, United States, 94598
      • John Muir Medical Center-Walnut Creek
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80301
      • Boulder Community Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80218
      • Exempla Saint Joseph Hospital
    • Denver, Colorado, United States, 80224-2522
      • Colorado Cancer Research Program CCOP
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Englewood, Colorado, United States, 80110
      • Rocky Mountain Gynecologic Oncology PC
    • Grand Junction, Colorado, United States, 81502
      • Saint Mary's Hospital and Regional Medical Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Littleton, Colorado, United States, 80122
      • Littleton Adventist Hospital
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
    • Thornton, Colorado, United States, 80229
      • North Suburban Medical Center
    • Wheat Ridge, Colorado, United States, 80033
      • SCL Health Lutheran Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami, Florida, United States, 33133
      • Mercy Hospital
    • Orlando, Florida, United States, 32803
      • Florida Hospital Orlando
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University Medical Center
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Savannah, Georgia, United States, 31404
      • Memorial University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Hinsdale, Illinois, United States, 60521
      • Sudarshan K Sharma MD Limted-Gynecologic Oncology
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Warrenville, Illinois, United States, 60555
      • Cadence Cancer Center in Warrenville
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology Oncology PC-Elkhart
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Oncology Center
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Saint Francis Health-Indianapolis
    • Indianapolis, Indiana, United States, 46237
      • Gynecologic Oncology of Indiana
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Mishawaka, Indiana, United States, 46545
      • Michiana Hematology Oncology PC-Mishawaka
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC-Plymouth
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • Michiana Hematology Oncology PC-South Bend
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium CCOP
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC-Westville
  • Iowa
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Des Moines, Iowa, United States, 50309
      • Iowa Oncology Research Association CCOP
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
    • Louisville, Kentucky, United States, 40202
      • Norton Hospital Pavilion and Medical Campus
    • Louisville, Kentucky, United States, 40202
      • The James Graham Brown Cancer Center at University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Bethesda, Maryland, United States, 20889-5600
      • Walter Reed National Military Medical Center
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Michigan
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Niles, Michigan, United States, 49120
      • Michiana Hematology Oncology PC-Niles
    • Reed City, Michigan, United States, 49677
      • Spectrum Health Reed City Hospital
    • Saint Joseph, Michigan, United States, 49085
      • Marie Yeager Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview-Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro-Minnesota NCI Community Oncology Research Program
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology and Hematology PA-Woodbury
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Springfield, Missouri, United States, 65804
      • Cancer Research for the Ozarks NCORP
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Women's Cancer Center of Nevada
    • Reno, Nevada, United States, 89502
      • Center of Hope at Renown Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • UMDNJ - Robert Wood Johnson University Hospital
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
    • Voorhees, New Jersey, United States, 08043
      • Virtua West Jersey Hospital Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Southwest Gynecologic Oncology Associates Inc
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico
    • Las Cruces, New Mexico, United States, 88011
      • Memorial Medical Center - Las Cruces
  • New York
    • Albany, New York, United States, 12208
      • Women's Cancer Care Associates LLC
    • Brooklyn, New York, United States, 11203
      • State University of New York Downstate Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Concord, North Carolina, United States, 28025
      • Carolinas HealthCare System NorthEast
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mentor, Ohio, United States, 44060
      • Lake University Ireland Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Tulsa Cancer Institute
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15224
      • West Penn Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-Magee Womens Hospital
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center-Oncology Clinic
  • Texas
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Dallas, Texas, United States, 75390
      • Clements University Hospital
    • Dallas, Texas, United States, 75235
      • Zale Lipshy University Hospital
    • Fort Worth, Texas, United States, 76104
      • Baylor All Saints Medical Center at Fort Worth
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm I Gem+Doce+Placebo; Patients receive a placebo IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim subcutaneously (SC) on days 9-15 or pegfilgrastim SC on day 9 or 10.	Drug: Docetaxel; Given IV; Other Names: Taxotere; RP56976; Taxotere Injection Concentrate; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: Gemzar; dFdCyd; Difluorodeoxycytidine Hydrochloride; LY-188011; Biological: Pegfilgrastim; Given SC; Other Names: Filgrastim SD-01; filgrastim-SD/01; Neulasta; SD-01; SD-01 sustained duration G-CSF; Biological: Filgrastim; Given SC; Other Names: G-CSF; r-metHuG-CSF; Neupogen; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; Filgrastim XM02; Tbo-filgrastim; Other: Placebo; Given IV; Other Names: placebo therapy; PLCB; sham therapy
EXPERIMENTAL: Arm II Gem+Doce+Bev; Patients receive bevacizumab IV over 30-90 minutes on day 1, gemcitabine hydrochloride IV over 90 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Patients also receive filgrastim SC on days 9-15 or pegfilgrastim SC on day 9 or 10.	Drug: Docetaxel; Given IV; Other Names: Taxotere; RP56976; Taxotere Injection Concentrate; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: Gemzar; dFdCyd; Difluorodeoxycytidine Hydrochloride; LY-188011; Biological: Pegfilgrastim; Given SC; Other Names: Filgrastim SD-01; filgrastim-SD/01; Neulasta; SD-01; SD-01 sustained duration G-CSF; Biological: Filgrastim; Given SC; Other Names: G-CSF; r-metHuG-CSF; Neupogen; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; Filgrastim XM02; Tbo-filgrastim; Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression free survival (PFS) was defined as the number of months between study enrollment and documentation of disease progression (RECIST 1.1) or death from any cause. Patients still alive and disease free at the last followup were censored on the date of last CT Scan. Assessed with a log-rank test stratified by whether the patient had whole pelvic radiotherapy prior to starting the study treatment. The product-limit method will be used to estimate the cumulative distribution of PFS for the patients assigned to each treatment group.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) was defined as the number of months between study enrollment and death from any cause. Patients still alive at the last followup were censored on the date of last CT Scan. The product-limit method will be used to estimate the cumulative distribution of overall survival times for the patients assigned to each treatment group.	Up to 5 years
Frequency and Severity of Adverse Effects as Assessed by the CTCAE Version 4.0	Count of participants with Adverse events (AEs) that are CTCAE Grade 3 or worse. Please refer to the adverse event reporting for more detail.	Up to 5 years
Objective Response Rate as Measured by RECIST 1.1 Criteria	"Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: Martee Hensley, NRG Oncology

Publications and helpful links

General Publications

• Kantidakis G, Litiere S, Neven A, Vinches M, Judson I, Schoffski P, Wardelmann E, Stacchiotti S, D'Ambrosio L, Marreaud S, van der Graaf WTA, Kasper B, Fiocco M, Gelderblom H. Efficacy thresholds for clinical trials with advanced or metastatic leiomyosarcoma patients: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group meta-analysis based on a literature review for soft-tissue sarcomas. Eur J Cancer. 2021 Sep;154:253-268. doi: 10.1016/j.ejca.2021.06.025. Epub 2021 Jul 20.
• Hensley ML, Miller A, O'Malley DM, Mannel RS, Behbakht K, Bakkum-Gamez JN, Michael H. Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: an NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2015 Apr 1;33(10):1180-5. doi: 10.1200/JCO.2014.58.3781. Epub 2015 Feb 23.

Helpful Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (ACTUAL): September 1, 2015
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: November 12, 2009
• First Submitted That Met QC Criteria: November 12, 2009
• First Posted (ESTIMATE): November 13, 2009

Study Record Updates

• Last Update Posted (ACTUAL): September 2, 2020
• Last Update Submitted That Met QC Criteria: August 20, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Neoplasms, Muscle Tissue; Sarcoma; Recurrence; Leiomyosarcoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Adjuvants, Immunologic; Gemcitabine; Docetaxel; Antibodies; Immunoglobulins; Bevacizumab; Lenograstim; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Immunoglobulin G; Endothelial Growth Factors
• Other Study ID Numbers: NCI-2010-01738 (REGISTRY: CTRP (Clinical Trial Reporting Program)); U10CA027469 (U.S. NIH Grant/Contract); CDR0000659024; GOG-0250 (OTHER: CTEP)