Phase III Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer
- Conditions
- Breast NeoplasmsNeoplasms, Hormone-dependent
- Interventions
- Drug: aromatase inhibitionProcedure: hormone therapyProcedure: endocrine therapyProcedure: antiestrogen therapy
- Registration Number
- NCT00044291
- Lead Sponsor
- Intarcia Therapeutics
- Brief Summary
The purpose of this study is to determine whether the first line combination hormonal therapy of an experimental drug, atamestane, plus an FDA-approved drug, toremifene (Fareston®), is more effective than another approved drug, letrozole (Femara®), in delaying the growth of breast cancer in postmenopausal patients with locally advanced or metastatic breast cancer, and whether the side effects of the combination are different from the side effects of letrozole.
- Detailed Description
Breast cancer cells are often very dependent on estrogens to continue to grow. Atamestane blocks the formation of estrogens and androgenic precursors in the body. Toremifene blocks circulating and intracellular estrogens from stimulating estrogen receptors in breast cancer cells. The goal of therapy with atamestane, an aromatase inhibitor, in combination with the estrogen receptor antagonist, toremifene, is to achieve maximal suppression of estrogen stimulation of breast cancer cells. This study is designed to determine whether combination therapy will lengthen the time to disease progression and the rate of objective response compared to single agent aromatase inhibitor therapy with letrozole.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 865
- Women age 18 years or older
- Pathological or histological confirmation of breast cancer at initial diagnosis or at the time of metastases
- ECOG performance status of 0, 1 or 2 or Karnofsky performance status of 60 or higher
- Predicted life expectancy of 12 weeks or more
- Postmenopausal endocrine status. LH/FSH levels in the postmenopausal range in women whose menopause occurred less than 5 years ago
- Locally recurrent, locally advanced, locally metastatic disease not amenable to radiation therapy or surgery and/or distant metastatic disease
- At least one tumor localization measurable in 2 dimensions (one diameter at least 2 cm for soft tissue/visceral disease assessed by CT/MRI scan or conventional X-ray technique, one diameter at least 1 cm for bone lesions assessed by conventional X-ray techniques)
- Estrogen receptor and/or progesterone receptor positive (by laboratory/institutional standard) at the time of initial diagnosis or determined during subsequent biopsy/surgery of metastases
- Written informed consent obtained
- Prior hormonal therapy to treat locally recurrent, locally advanced or metastatic disease
- Prior adjuvant therapy with aromatase inhibitors or antiestrogens/SERMs within 12 months prior to enrollment
- Progression of disease during therapy with antiestrogens (including SERMs administered for prevention of osteoporosis)
- Life-threatening locally recurrent, locally advanced or metastatic disease or disease requiring chemotherapeutic intervention (such as inflammatory breast cancer)
- History of known CNS metastases, significant neurological dysfunction including active seizures, or clinical signs of other significant neurological diseases
- Other active malignancy (except basal cell carcinoma of the skin or in situ cervical cancer). Patients with previous malignancies must be without evidence of disease for at least five years
- Renal insufficiency (serum creatinine > 2.0 mg/dL)
- Aspartate aminotransferase, alanine aminotransferase or serum bilirubin levels more than 2.5 times upper limit of normal
- Hemoglobin <9 g/dL
- Platelet count of less than 100,000 platelets per mm3
- Total white blood cell count of less than 2,000 cells per mm3
- Premenopausal endocrine status; pregnant or lactating females
- Usage of an investigational drug within the thirty (30) days prior to enrollment; or the planned usage of an investigational drug other than the study medication during the course of the current study
- Contraindication to use of toremifene, atamestane, letrozole or any of the inactive components of their formulations
- Prior enrollment in this study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atamestane + toremifene antiestrogen therapy - Letrozole + placebo aromatase inhibition - Letrozole + placebo hormone therapy - Letrozole + placebo endocrine therapy - Atamestane + toremifene toremifene - Atamestane + toremifene aromatase inhibition - Atamestane + toremifene hormone therapy - Atamestane + toremifene endocrine therapy - Atamestane + toremifene atamestane - Letrozole + placebo letrozole -
- Primary Outcome Measures
Name Time Method Time to tumor progression time from randomization to first occurrence of tumor progression, assessed at week 12 and every subsequent 12 weeks for patients continuing in the study for up to approximately 36 months
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (63)
Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department. Clinical Facility: Kharkov Regional Clinical Oncology Dispensary, Chemotherapy Department
🇺🇦Kharkov, Ukraine
Odessa State Medical University, Oncology Department. Clinical Facility: Odessa Regional Oncology Center, Chemotherapy Department
🇺🇦Odessa, Ukraine
V. Novgorod Regional Oncology Center, Department of Chemotherapy
🇷🇺V. Novgorod, Russian Federation
Burdenko Voronezh Medical Academy, Oncology Department, Clinical Facility: Regional Clinical Oncology Center
🇷🇺Voronezh, Russian Federation
Midwest Internal Medicine, PLLC
🇺🇸Lake Havasu City, Arizona, United States
Great Falls Clinic-Oncology West
🇺🇸Great Falls, Montana, United States
Northwestern Ontario Regional Cancer Centre
🇨🇦Thunder Bay, Ontario, Canada
Cache Valley Cancer Treatment & Research Clinic
🇺🇸Logan, Utah, United States
Stavropol Regional Oncology Center, Department of Chemotherapy
🇷🇺Stavropol, Russian Federation
Samara Regional Oncology Center, Department of Chemotherapy
🇷🇺Samara, Russian Federation
Petrov Research Institute of Oncology, Department of Breast Cancer
🇷🇺St. Petersburg, Russian Federation
Dnepropetrovsk State Medical Academy, Oncology Department. Clinical Facility: Dnepropetrovsk City Clinical Hospital #4
🇺🇦Dnepropetrovsk, Ukraine
Arizona Clinical Research Center
🇺🇸Tucson, Arizona, United States
California Cancer Care, Inc.
🇺🇸Greenbrae, California, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Georgia Cancer Specialists
🇺🇸Tucker, Georgia, United States
Maryland Hematology/Oncology Associates
🇺🇸Baltimore, Maryland, United States
Oncology Care Associates, PLLC
🇺🇸St. Joseph, Michigan, United States
Kansas City Oncology and Hematology Group
🇺🇸Kansas City, Missouri, United States
Oncology Consultants
🇺🇸Houston, Texas, United States
First Dynamic Healthcare Services, Inc.
🇺🇸Killeen, Texas, United States
Slocum-Dickson Medical Group
🇺🇸New Hartford, New York, United States
Western Washington Oncology Inc., P.S.
🇺🇸Olympia, Washington, United States
Hematology Oncology Consultants, Inc.
🇺🇸Columbus, Ohio, United States
Ottawa Regional Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Arkhangelsk Regional Oncology Center, Department of Chemotherapy
🇷🇺Arkhangelsk, Russian Federation
Krasnodar Regional Clinical Oncology Center, Chemotherapy Department
🇷🇺Krasnodar, Russian Federation
McGill University, Department of Oncology
🇨🇦Montreal, Quebec, Canada
Leningrad Regional Oncology Center
🇷🇺Leningrad, Russian Federation
Tatarstan Republican Clinical Oncology Center
🇷🇺Kazan, Russian Federation
Lipetsk Regional Oncology Center, Department of General Oncology
🇷🇺Lipetsk, Russian Federation
Blokhin Cancer Research Center, Department of Chemotherapy and Combined Treatment of Tumors
🇷🇺Moscow, Russian Federation
Blokhin Cancer Research Center, Department of New Antitumor Drug Research
🇷🇺Moscow, Russian Federation
Blokhin Cancer Research Center, Department of Chemotherapy
🇷🇺Moscow, Russian Federation
Blokhin Cancer Research Center, Department of Clinical Pharmacology and Chemotherapy
🇷🇺Moscow, Russian Federation
Moscow City Hospital #40, Department of Chemotherapy
🇷🇺Moscow, Russian Federation
Hertzen Research Institute of Oncology, Department of Chemotherapy
🇷🇺Moscow, Russian Federation
Central Clinical Hospital of the Ministry of Transport n.a. Semashko, Department of Chemotherapy
🇷🇺Moscow, Russian Federation
Moscow City Oncology Hospital #62
🇷🇺Moscow, Russian Federation
Medical Radiological Research Center
🇷🇺Obninsk, Russian Federation
Murmansk Regional Oncology Center
🇷🇺Murmansk, Russian Federation
St. Petersburg City Oncology Center
🇷🇺St. Petersburg, Russian Federation
Ryazan Regional Clinical Oncology Center
🇷🇺Ryazan, Russian Federation
Municipal Clinical Hospital #1, Department of Breast Tumors, Oncology Department
🇷🇺Novosibirsk, Russian Federation
Laboratory of Thoracic Oncology, St. Petersburg Pavlov State Medical University, Research Institute of Pulmonology
🇷🇺St. Petersburg, Russian Federation
Petrov Research Institute of Oncology, Department of Biotherapy and Bone Marrow Transplantation
🇷🇺St. Petersburg, Russian Federation
Petrov Research Institute of Oncology, Department of Chemotherapy
🇷🇺St. Petersburg, Russian Federation
Donetsk State Medical University. Clinical Facility: Donetsk Regional Antineoplastic Center, Mammology Department
🇺🇦Donetsk, Ukraine
Cherkassy Regional Oncology Center, Chemotherapy Department
🇺🇦Cherkassy, Ukraine
Ivano-Frankovsk State Medical Academy; Oncology Department Clinical Facility: Ivano-Frankovsk Regional Oncology Center
🇺🇦Ivano-Frankovsk, Ukraine
Kharkov State Medical University. Clinical Facility: Grigoriev Medical Radiology Institute, Chemotherapy Department
🇺🇦Kharkov, Ukraine
Kiev Central Clinical Hospital, Ukraine Security Services, Surgery Department
🇺🇦Kiev, Ukraine
Kiev Oncology Institute, Ukraine Medical Science Academy, Department of Breast Tumors
🇺🇦Kiev, Ukraine
National Medical University, Oncology Department. Clinical Facility: Kiev City Oncology Hospital, Surgery Department
🇺🇦Kiev, Ukraine
Innovative Medical Research of South Florida Inc.
🇺🇸Miami Shores, Florida, United States
Research Institute of Oncology, Tomsk Scientific Center, Siberian Department of the Russian Academy of Medical Sciences, Department of Chemotherapy
🇷🇺Tomsk, Russian Federation
Kiev Postgraduate Studies Medical Academy. Clinical Facility: Kiev City Oncology Hospital, Chemotherapy Department
🇺🇦Kiev, Ukraine
Krivoy Rog City Oncology Center
🇺🇦Krivoy Rog, Ukraine
Uzhgorod National University Oncology Course of Surgery Department of Postgraduate Education Faculty Clinical Facility: Zakarpatye Regional Oncology Center
🇺🇦Uzhgorod, Ukraine
Zaporozhye Statue Institute of Postgraduate Training. Oncology Department; Clinical Facility: Zaporozhye Regional Oncology Center
🇺🇦Zaporozhye, Ukraine
Lviv State Medical University, Oncology and Medical Radiology Department. Clinical Facility: Lviv State Oncology Regional Clinical Diagnostic Center, Chemotherapy Department
🇺🇦Lviv, Ukraine
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada