Know Cancer

or
forgot password

A Randomized Phase II Trial of Combination Anastrozole (NSC #719344) Plus ZD1839 (Iressa, NSC #715055, IND #61187) and of Combination Fulvestrant (NSC #719276) Plus ZD1839 in the Treatment of Postmenopausal Women With Hormone Receptor-Positive Metastatic Breast Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Breast Cancer

Thank you

Trial Information

A Randomized Phase II Trial of Combination Anastrozole (NSC #719344) Plus ZD1839 (Iressa, NSC #715055, IND #61187) and of Combination Fulvestrant (NSC #719276) Plus ZD1839 in the Treatment of Postmenopausal Women With Hormone Receptor-Positive Metastatic Breast Cancer


OBJECTIVES:

- Compare the antitumor activity of anastrozole and gefitinib vs fulvestrant and
gefitinib in postmenopausal women with recurrent or metastatic hormone
receptor-positive breast cancer.

- Compare the safety of these regimens in these patients.

- Compare the interaction of biological predictors of response in patients treated with
these regimens.

OUTLINE: This is a randomized, open-label study. Patients are stratified according to prior
hormonal therapy (yes vs. no) and dominant site of disease (soft tissue/lymph nodes vs. bone
vs. visceral). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral anastrozole and oral gefitinib once daily on days 1-28.

- Arm II: Patients receive fulvestrant intramuscularly on day 1 and oral gefitinib once
daily on days 1-28.

Courses in both arms repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

ACCRUAL: A total of 148 patients (74 per treatment arm) were accrued for this study.

Inclusion Criteria


Inclusion criteria:

- Histologically confirmed adenocarcinoma of the breast (Recurrent or metastatic
disease)

- Measurable disease

- Patients with available tissue blocks from either the primary or metastatic site must
submit the tissue for epidermal growth factor receptor analysis

- Estrogen and/or progesterone receptor positive

- Age>=18

- Female

- Postmenopausal, defined by 1 of the following:

- Prior bilateral oophorectomy or bilateral ovarian irradiation

- No menstrual period for at least 12 months

NOTE: If age 55 and under and on tamoxifen within the past 6 months, must have an
estradiol level in the postmenopausal range

- ECOG performance status of 0-2

- Adequate hematopoietic, hepatic, renal functions defined by the following within 2
weeks prior to randomization:

- Neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Bilirubin no greater than 1.25 times upper limit of normal (ULN)

- Serum glutamic-pyruvic transaminase (ALT) and Serum glutamic-oxaloacetic (AST)
no greater than 2.5 times ULN (5 times ULN if liver metastases are present)

- International normalized ratio of prothrombin time (INR), prothrombin time (PT),
and partial thromboplastin time (PTT) normal

- Creatinine clearance at least 30 mL/min

- More than 3 weeks since prior trastuzumab (Herceptin®)

- More than 3 weeks since prior chemotherapy

- More than 3 months since prior luteinizing hormone-releasing hormone agonists or
antagonists (patients 55 years old and under)

- Recovered from prior radiotherapy

- Concurrent radiotherapy to painful sites of bony disease or areas of impending
fracture is allowed provided the following conditions are met:

- Therapy was initiated prior to study entry

- Sites of measurable disease outside the radiotherapy port are available for
disease evaluation

- Concurrent bisphosphonates for hypercalcemia or bone metastases are allowed

Exclusion Criteria:

- Pregnant or nursing

- Untreated ocular inflammation or infection

- Medical or psychiatric condition that would preclude study compliance, ability to
give informed consent, or assessment of response or anticipated toxic effects

- History of central nervous system (CNS) metastasis

- Other invasive malignancies within the past 5 years except curatively treated basal
cell or squamous cell skin cancer or carcinoma in situ of the cervix

- Contraindication to intramuscular injections

- More than 2 prior chemotherapy regimens for metastatic disease

- Prior hormonal therapy for metastatic disease

- Prior estrogen receptor down-regulators (e.g., fulvestrant) in the adjuvant setting

- Prior aromatase inhibitors (e.g., anastrozole, letrozole, exemestane, or
aminoglutethimide) in the adjuvant setting

- Prior agents that target epidermal growth factor receptors

- Other concurrent hormonal therapy

- Concurrent chemotherapy

- Concurrent trastuzumab

- Concurrent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
(e.g., ketoconazole, erythromycin, or verapamil)

- Concurrent anticoagulants, except for thrombotic events in patients in arm I

- Concurrent medications that would alter the pharmacokinetics of gefitinib (e.g.,
phenytoin, carbamazepine, phenobarbital, rifampin, Hypericum perforatum [St. John's
wort], oxcarbazepine, rifapentine, modafinil, and griseofulvin)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical Benefit Rate

Outcome Description:

Clinical benefit = complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 6 months, assessed per Response Evaluation Criteria of Solid Tumor (RECIST).CR=disappearance of all target and non-target lesions. PR= disappearance of or at least 30% decrease in the sum of the longest diameters of target lesions, with non-progressive disease in non-target lesions. SD= sum of the longest diameters of target lesions decrease <30% or increase <20%, with non-progressive disease in non-target lesions. 141 eligible, treated patients were included.

Outcome Time Frame:

assessed every 3 cycles while on treatment, assessed every 3 months when follow up <2 years, every 6 months between 2-3 years,no specific requirements after 3 years

Safety Issue:

No

Principal Investigator

Robert W. Carlson, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Stanford University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03148

NCT ID:

NCT00057941

Start Date:

September 2003

Completion Date:

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage IV breast cancer
  • metastatic breast cancer
  • postmenopausal women
  • hormone receptor-positive
  • Breast Neoplasms

Name

Location

Hurley Medical CenterFlint, Michigan  48503
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Carle Cancer CenterUrbana, Illinois  61801
CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
CCOP - Colorado Cancer Research ProgramDenver, Colorado  80224-2522
Porter Adventist HospitalDenver, Colorado  80210
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
St. Joseph HospitalDenver, Colorado  80218
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical CenterGrand Junction, Colorado  81502
Sky Ridge Medical CenterLone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United HospitalLongmont, Colorado  80502
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
North Suburban Medical CenterThornton, Colorado  80229
Rush-Copley Cancer Care CenterAurora, Illinois  60507
Hinsdale Hematology Oncology AssociatesHinsdale, Illinois  60521
Joliet Oncology-Hematology Associates, Limited - WestJoliet, Illinois  60435
Carle Cancer Center at Carle Foundation HospitalUrbana, Illinois  61801
Saint Anthony Memorial Health CentersMichigan City, Indiana  46360
Cedar Rapids Oncology AssociatesCedar Rapids, Iowa  52403
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
Tufts-NEMC Cancer CenterBoston, Massachusetts  02111
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical CenterDearborn, Michigan  48123-2500
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Foote HospitalJackson, Michigan  49201
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Sparrow Regional Cancer CenterLansing, Michigan  48912-1811
Seton Cancer Institute - SaginawSaginaw, Michigan  48601
St. John Macomb HospitalWarren, Michigan  48093
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Duluth Clinic Cancer Center - DuluthDuluth, Minnesota  55805-1983
CCOP - DuluthDuluth, Minnesota  55805
Miller - Dwan Medical CenterDuluth, Minnesota  55805
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
Meeker County Memorial HospitalLichfield, Minnesota  55355
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
HealthEast Cancer Care at St. Joseph's HospitalSt Paul, Minnesota  55102
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
HealthEast Cancer Care at Woodwinds Health CampusWoodbury, Minnesota  55125
MetroHealth Cancer Care Center at MetroHealth Medical CenterCleveland, Ohio  44109
St. Rita's Medical CenterLima, Ohio  45801
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Geisinger Medical Group - Scenery ParkState College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical CenterWilkes-Barre, Pennsylvania  18711
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PCSioux Falls, South Dakota  57105
Avera Cancer InstituteSioux Falls, South Dakota  57105
Dean Medical Center - MadisonMadison, Wisconsin  53717
CCOP - OchsnerNew Orleans, Louisiana  70121
CCOP - ColumbusColumbus, Ohio  43206
Mercy Hospital Cancer Center - ScrantonScranton, Pennsylvania  18501
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
Overlook HospitalSummit, New Jersey  07902-0220
Carol G. Simon Cancer Center at Morristown Memorial HospitalMorristown, New Jersey  07962
Ochsner Cancer Institute at Ochsner Clinic FoundationNew Orleans, Louisiana  70121
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
McCreery Cancer Center at Ottumwa RegionalOttumwa, Iowa  52501
Green Bay Oncology, Limited - EscanabaEscanaba, Michigan  49431
Dickinson County Healthcare SystemIron Mountain, Michigan  49801
Our Lady of Mercy Medical Center Comprehensive Cancer CenterBronx, New York  10466
Lewistown HospitalLewistown, Pennsylvania  17044
Mount Nittany Medical CenterState College, Pennsylvania  16803
Chester County HospitalWest Chester, Pennsylvania  19380
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto FallsOconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon BaySturgeon Bay, Wisconsin  54235
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Baptist Cancer Institute - JacksonvilleJacksonville, Florida  32207
Adena Regional Medical CenterChillicothe, Ohio  54601
Doctors Hospital at Ohio HealthColumbus, Ohio  43228
Riverside Methodist Hospital Cancer CareColumbus, Ohio  43214
Grady Memorial HospitalDelaware, Ohio  43015
Fairfield Medical CenterLancaster, Ohio  43130
Strecker Cancer Center at Marietta Memorial HospitalMarietta, Ohio  45750
Licking Memorial Cancer Care Program at Licking Memorial HospitalNewark, Ohio  43055
Community Hospital of Springfield and Clark CountySpringfield, Ohio  45505
Genesis - Good Samaritan HospitalZanesville, Ohio  43701
Decatur Memorial Hospital Cancer Care InstituteDecatur, Illinois  62526
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital MarltonMarlton, New Jersey  08053
Fox Chase Virtua Health Cancer Program at Virtua West JerseyVoorhees, New Jersey  08043
Mount Carmel Health - West HospitalColumbus, Ohio  43222
Joan Karnell Cancer Center at Pennsylvania HospitalPhiladelphia, Pennsylvania  19107
John Stoddard Cancer Center at Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Mercy Capitol HospitalDes Moines, Iowa  50307
Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer CenterDes Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates - West Des MoinesWest Des Moines, Iowa  50266
Terrebonne General Medical CenterHouma, Louisiana  70360
Mountainside Hospital Cancer CenterMontclair, New Jersey  07042
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Mercy Medical CenterSpringfield, Ohio  45504
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Trinity Medical CenterMoline, Illinois  61265-1291
Morton Hospital & Medical CenterTaunton, Massachusetts  02780
Pottstown Memorial Regional Cancer CenterPottstown, Pennsylvania  19464
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/CandlerSavannah, Georgia  31405
Ochsner Health Center - BluebonnetBaton Rouge, Louisiana  70809
Union Hospital Cancer Program at Union HospitalElkton MD, Maryland  21921
Grant Medical Center Cancer CareColumbus, Ohio  43215
Mount Carmel St. Ann's Cancer CenterWesterville, Ohio  43081
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
Hematology and Oncology Associates of Northeastern PennsylvaniaScranton, Pennsylvania  18510
Regional Cancer Center at Memorial Medical CenterSpringfield, Illinois  62781-0001
Stanford Comprehensive Cancer Center - StanfordStanford, California  94305
Shore Memorial Hospital - Somers PointSomers Point, New Jersey  08244
Alexian Brothers Radiation OncologyElk Grove Village, Illinois  60007
Elmhurst Memorial HospitalElmhurst, Illinois  60126
Trinity Cancer Center at Trinity Medical Center - 7th Street CampusMoline, Illinois  61265
Hattiesburg Clinic, PA at Forrest GeneralHattiesburg, Mississippi  39401
Saints Memorial Cancer Center at Saints Memorial Medical CenterLowell, Massachusetts  01852
Hematology & Oncology ClinicHattiesburg, Mississippi  39402
Fawcett Memorial HospitalPort Charlotte, Florida  33952
Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett HospitalCooperstown, New York  13326