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A Randomized Phase III Evaluation of Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF With Bevacizumab (NSC #704865, IND #7921) Versus Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF With Placebo in the Treatment of Recurrent or Advanced Leiomyosarcoma of the Uterus


Phase 3
18 Years
N/A
Open (Enrolling)
Female
Recurrent Uterine Sarcoma, Stage IIIA Uterine Sarcoma, Stage IIIB Uterine Sarcoma, Stage IIIC Uterine Sarcoma, Stage IVA Uterine Sarcoma, Stage IVB Uterine Sarcoma, Uterine Leiomyosarcoma

Thank you

Trial Information

A Randomized Phase III Evaluation of Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF With Bevacizumab (NSC #704865, IND #7921) Versus Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF With Placebo in the Treatment of Recurrent or Advanced Leiomyosarcoma of the Uterus


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Duration of progression-free survival

Outcome Description:

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.

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Martee Hensley

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2010-01738

NCT ID:

NCT01012297

Start Date:

November 2009

Completion Date:

Related Keywords:

  • Recurrent Uterine Sarcoma
  • Stage IIIA Uterine Sarcoma
  • Stage IIIB Uterine Sarcoma
  • Stage IIIC Uterine Sarcoma
  • Stage IVA Uterine Sarcoma
  • Stage IVB Uterine Sarcoma
  • Uterine Leiomyosarcoma
  • Leiomyosarcoma
  • Sarcoma

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205
Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Cleveland Clinic FoundationCleveland, Ohio  44195
Mayo ClinicRochester, Minnesota  55905
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Abington Memorial HospitalAbington, Pennsylvania  19001
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Medical University of South CarolinaCharleston, South Carolina  29425-0721
Pennsylvania HospitalPhiladelphia, Pennsylvania  19107
Boulder Community HospitalBoulder, Colorado  80301-9019
Porter Adventist HospitalDenver, Colorado  80210
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
Sky Ridge Medical CenterLone Tree, Colorado  80124
North Suburban Medical CenterThornton, Colorado  80229
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Fairview Ridges HospitalBurnsville, Minnesota  55337
Hutchinson Area Health CareHutchinson, Minnesota  55350
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Avera Cancer InstituteSioux Falls, South Dakota  57105
Morristown Memorial HospitalMorristown, New Jersey  07962-1956
Memorial Hospital of South BendSouth Bend, Indiana  46601
Lehigh Valley HospitalAllentown, Pennsylvania  18103
Western Pennsylvania HospitalPittsburgh, Pennsylvania  15224
Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
Rush University Medical CenterChicago, Illinois  60612-3824
University of Kansas Medical CenterKansas City, Kansas  66160-7353
Hartford HospitalHartford, Connecticut  06102-5037
Franklin Square Hospital CenterBaltimore, Maryland  21237
Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
MetroHealth Medical CenterCleveland, Ohio  44109
Mount Sinai Medical CenterNew York, New York  10029
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Munson Medical CenterTraverse City, Michigan  49684
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Mercy HospitalMiami, Florida  33133
Elkhart General HospitalElkhart, Indiana  46515
Gynecologic Oncology of IndianaIndianapolis, Indiana  46237
South Bend ClinicSouth Bend, Indiana  46617
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Beebe Medical CenterLewes, Delaware  19958
Mecosta County Medical CenterBig Rapids, Michigan  49307
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Mercy HospitalCoon Rapids, Minnesota  55433
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Fairview-Southdale HospitalEdina, Minnesota  55435
Abbott-Northwestern HospitalMinneapolis, Minnesota  55407
Regions HospitalSaint Paul, Minnesota  55101
Saint Francis Regional Medical CenterShakopee, Minnesota  55379
Rice Memorial HospitalWillmar, Minnesota  56201
Geisinger Medical GroupState College, Pennsylvania  16801
Longmont United HospitalLongmont, Colorado  80501
Aurora Sinai Medical CenterMilwaukee, Wisconsin  53201-0342
Greater Baltimore Medical CenterBaltimore, Maryland  21204
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Presbyterian HospitalCharlotte, North Carolina  28233-3549
Mayo Clinic in FloridaJacksonville, Florida  32224
Washington Hospital CenterWashington, District of Columbia  20010
Memorial Medical CenterSpringfield, Illinois  62781
Metro Health HospitalGrand Rapids, Michigan  49506
Duke University Medical CenterDurham, North Carolina  27710
Northwestern UniversityChicago, Illinois  60611
Hennepin County Medical CenterMinneapolis, Minnesota  
University of California at San DiegoLa Jolla, California  92093
Case Western Reserve UniversityCleveland, Ohio  44106
Wayne State UniversityDetroit, Michigan  48202
Riverside Methodist HospitalColumbus, Ohio  43214
Dartmouth Hitchcock Medical CenterLebanon, New Hampshire  03756
Indiana University Medical CenterIndianapolis, Indiana  46202
Presbyterian - Saint Lukes Medical Center - Health OneDenver, Colorado  80218
University of Texas Southwestern Medical CenterDallas, Texas  
Huntsman Cancer Institute/University of UtahSalt Lake City, Utah  84112
Metro-Minnesota CCOPSt. Louis Park, Minnesota  
Lakeview HospitalStillwater, Minnesota  55082
Providence Saint Joseph Medical CenterBurbank, California  91505-4866
Florida HospitalOrlando, Florida  32803
Memorial Health University Medical CenterSavannah, Georgia  31404
Hillcrest Hospital Cancer CenterMayfield Heights, Ohio  44124
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
M D Anderson Cancer CenterHouston, Texas  77030
University of Southern CaliforniaLos Angeles, California  90033
Northern Indiana Cancer Research ConsortiumSouth Bend, Indiana  
University of CincinnatiCincinnati, Ohio  45267-0502
Penn State Milton S Hershey Medical CenterHershey, Pennsylvania  17033
Littleton Adventist HospitalLittleton, Colorado  80122
Parker Adventist HospitalParker, Colorado  80138
New Ulm Medical CenterNew Ulm, Minnesota  56073
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
University of California San Francisco Medical Center-Mount ZionSan Francisco, California  94115
The Medical Center of AuroraAurora, Colorado  80012
Penrose-Saint Francis HealthcareColorado Springs, Colorado  80907
Saint Anthony Central HospitalDenver, Colorado  80204
Exempla Saint Joseph HospitalDenver, Colorado  80218
Colorado Cancer Research Program CCOPDenver, Colorado  80224-2522
Saint Mary's Hospital and Regional Medical CenterGrand Junction, Colorado  81502
Saint Mary Corwin Medical CenterPueblo, Colorado  81004
The Hospital of Central ConnecticutNew Britain, Connecticut  06050
M D Anderson Cancer Center- OrlandoOrlando, Florida  32806
John B Amos Cancer CenterColumbus, Georgia  31904
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309
Grand Rapids Clinical Oncology ProgramGrand Rapids, Michigan  49503
Saint Mary's Health CareGrand Rapids, Michigan  49503
Spectrum Health at Butterworth CampusGrand Rapids, Michigan  49503
Mercy Health Partners-Mercy CampusMuskegon, Michigan  49443
Lakeland HospitalSt. Joseph, Michigan  49085
Unity HospitalFridley, Minnesota  55432
Saint John's Hospital - HealtheastMaplewood, Minnesota  55109
Minnesota Oncology Hematology PA-MaplewoodMaplewood, Minnesota  55109
North Memorial Medical Health CenterRobbinsdale, Minnesota  55422
Park Nicollet Clinic - Saint Louis ParkSaint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-WoodburyWoodbury, Minnesota  55125
Ozark Health Ventures LLC dba Cancer Research for The Ozarks SpringfieldSpringfield, Missouri  65802
Saint John's HospitalSpringfield, Missouri  65804
Cox Medical CenterSpringfield, Missouri  65807
Cooper Hospital University Medical CenterCamden, New Jersey  08103
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington CountyMount Holly, New Jersey  08060
Memorial Medical Center - Las CrucesLas Cruces, New Mexico  88011
Kettering Medical CenterKettering, Ohio  45429
Geisinger Wyoming ValleyWilkes-Barre, Pennsylvania  18711
Sanford Cancer Center-Oncology ClinicSioux Falls, South Dakota  57104
University of California Medical Center At Irvine-Orange CampusOrange, California  92868
Cancer Care Associates-YaleTulsa, Oklahoma  74136-1929
Women and Infants HospitalProvidence, Rhode Island  02905
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
Lake University Ireland Cancer CenterMentor, Ohio  44060
Magee-Womens Hospital of UPMCPittsburgh, Pennsylvania  15213
Stony Brook University Medical CenterStony Brook, New York  11794
Elkhart ClinicElkhart, Indiana  46515
John Muir Medical Center-Concord CampusConcord, California  94520
University of Colorado Cancer Center - Anschutz Cancer PavilionAurora, Colorado  80045
Michiana Hematology Oncology PC-ElkhartElkhart, Indiana  46514
Michiana Hematology Oncology PC-PlymouthPlymouth, Indiana  46563
Michiana Hematology Oncology PC-South BendSouth Bend, Indiana  46601
Michiana Hematology Oncology-PC WestvilleWestville, Indiana  46391
Michiana Hematology Oncology PC-NilesNiles, Michigan  49120
Carolinas Medical Center - NortheastConcord, North Carolina  28025
Olive View-University of California Los Angeles Medical CenterSylmar, California  91342
Center of Hope at Renown Medical CenterReno, Nevada  89502
State University of New York Downstate Medical CenterBrooklyn, New York  11203
Aurora Women's Pavilion of Aurora West Allis Medical CenterWest Allis, Wisconsin  53227
Kaiser Permanente Los Angeles Medical CenterLos Angeles, California  90027
Rocky Mountain Gynecologic Oncology PCEnglewood, Colorado  80110
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida  33136
Norton Health Care Pavilion - DowntownLouisville, Kentucky  40202
Southwest Gynecologic Oncology Associates IncAlbuquerque, New Mexico  87106
Women's Cancer Center of NevadaLas Vegas, Nevada  89109
Central DuPage Hospital Cancer CenterWarrenville, Illinois  60555
Spectrum Health Reed City HospitalReed City, Michigan  49677
Walter Reed National Military Medical CenterBethesda, Maryland  20889
Palo Alto Medical Foundation-Gynecologic OncologyMountain View, California  94040
Sudarshan K Sharma MD Limted-Gynecologic OncologyHinsdale, Illinois  60521
Saint Vincent Oncology CenterIndianapolis, Indiana  46260
Aurora Saint Luke's Medical CenterMilwaukee, Wisconsin  53215
Jonsson Comprehensive Cancer CenterLos Angeles, California  90095
Michiana Hematology Oncology PC-MishawakaMishawaka, Indiana  46545-1470
Marie Yeager Cancer CenterSaint Joseph, Michigan  49085
Summa Akron City HospitalAkron, Ohio  44304
Gynecologic Oncology GroupPhiladelphia, Pennsylvania  19103
Sanford USD Medical Center - Sioux FallsSioux Falls, South Dakota  57117-5134
Geisinger Medical Center-Cancer Center HazeltonHazleton, Pennsylvania  18201
Community Howard Regional HealthKokomo, Indiana  46904
Indiana University Health La Porte HospitalLa Porte, Indiana  46350
Saint Joseph Regional Medical Center-MishawakaMishawaka, Indiana  46545-1470
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718
Bronson Battle CreekBattle Creek, Michigan  49017
Georgia Regents UniversityAugusta, Georgia  30912
Cleveland Clinic Cancer Center/Fairview HospitalCleveland, Ohio  44111
Saint Joseph's Hospital and Medical CenterPhoenix, Arizona  85013
Kaiser Permanente Medical Care Program - Los Angeles Medical Center & Sunset HospitalLos Angeles, California  90027
The James Graham Brown Cancer Center at University of LouisvilleLouisville, Kentucky  40202
Women's Cancer Care Associates LLCAlbany, New York  12208
Fletcher Allen Health Care-Medical CenterBurlington, Vermont  05401
Cancer Center of Western WisconsinNew Richmond, Wisconsin  54017
Baylor All Saints Medical Center at Fort WorthFort Worth, Texas  76104
Baptist Health LexingtonLexington, Kentucky  40503
Lahey Hospital and Medical CenterBurlington, Massachusetts  01805