Clinical trial NCT00044291: Phase III Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Neoplasms
Neoplasms, Hormone-dependent
Keywords: Atamestane
Toremifene
Letrozole
Aromatase inhibitor
Receptor-positive
First line therapy
Estrogen blocker
Metastatic breast cancer
Locally advanced breast cancer
Locally recurrent breast cancer
stage IV breast cancer
ductal breast carcinoma
lobular breast carcinoma
stage IIIA breast cancer
stage IIIB breast cancer
recurrent breast cancer
Lead sponsor: Intarcia Therapeutics
Sponsor class: INDUSTRY
First posted: 2002-08-27
Enrollment: 865
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Time to tumor progression
timeFrame: 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 outcomes:
Other outcomes:
Locations:
city: Lake Havasu City
country: United States
facility: Midwest Internal Medicine, PLLC
state: Arizona
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Greenbrae
country: United States
facility: California Cancer Care, Inc.
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Miami Shores
country: United States
facility: Innovative Medical Research of South Florida Inc.
state: Florida
city: Tucker
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Baltimore
country: United States
facility: Maryland Hematology/Oncology Associates
state: Maryland
city: St. Joseph
country: United States
facility: Oncology Care Associates, PLLC
state: Michigan
city: Kansas City
country: United States
facility: Kansas City Oncology and Hematology Group
state: Missouri
city: Great Falls
country: United States
facility: Great Falls Clinic-Oncology West
state: Montana
city: New Hartford
country: United States
facility: Slocum-Dickson Medical Group
state: New York
city: Columbus
country: United States
facility: Hematology Oncology Consultants, Inc.
state: Ohio
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: Killeen
country: United States
facility: First Dynamic Healthcare Services, Inc.
state: Texas
city: Logan
country: United States
facility: Cache Valley Cancer Treatment & Research Clinic
state: Utah
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Olympia
country: United States
facility: Western Washington Oncology Inc., P.S.
state: Washington
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Thunder Bay
country: Canada
facility: Northwestern Ontario Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University, Department of Oncology
state: Quebec
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Oncology Center, Department of Chemotherapy
city: Kazan
country: Russian Federation
facility: Tatarstan Republican Clinical Oncology Center
city: Krasnodar
country: Russian Federation
facility: Krasnodar Regional Clinical Oncology Center, Chemotherapy Department
city: Leningrad
country: Russian Federation
facility: Leningrad Regional Oncology Center
city: Lipetsk
country: Russian Federation
facility: Lipetsk Regional Oncology Center, Department of General Oncology
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center, Department of Chemotherapy and Combined Treatment of Tumors
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center, Department of Chemotherapy
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center, Department of Clinical Pharmacology and Chemotherapy
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center, Department of New Antitumor Drug Research
city: Moscow
country: Russian Federation
facility: Hertzen Research Institute of Oncology, Department of Chemotherapy
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital of the Ministry of Transport n.a. Semashko, Department of Chemotherapy
city: Moscow
country: Russian Federation
facility: Moscow City Hospital #40, Department of Chemotherapy
city: Moscow
country: Russian Federation
facility: Moscow City Oncology Hospital #62
city: Murmansk
country: Russian Federation
facility: Murmansk Regional Oncology Center
city: Novosibirsk
country: Russian Federation
facility: Municipal Clinical Hospital #1, Department of Breast Tumors, Oncology Department
city: Obninsk
country: Russian Federation
facility: Medical Radiological Research Center
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Oncology Center
city: Samara
country: Russian Federation
facility: Samara Regional Oncology Center, Department of Chemotherapy
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg City Oncology Center
city: St. Petersburg
country: Russian Federation
facility: Laboratory of Thoracic Oncology, St. Petersburg Pavlov State Medical University, Research Institute of Pulmonology
city: St. Petersburg
country: Russian Federation
facility: Petrov Research Institute of Oncology, Department of Biotherapy and Bone Marrow Transplantation
city: St. Petersburg
country: Russian Federation
facility: Petrov Research Institute of Oncology, Department of Breast Cancer
city: St. Petersburg
country: Russian Federation
facility: Petrov Research Institute of Oncology, Department of Chemotherapy
city: Stavropol
country: Russian Federation
facility: Stavropol Regional Oncology Center, Department of Chemotherapy
city: Tomsk
country: Russian Federation
facility: Research Institute of Oncology, Tomsk Scientific Center, Siberian Department of the Russian Academy of Medical Sciences, Department of Chemotherapy
city: V. Novgorod
country: Russian Federation
facility: V. Novgorod Regional Oncology Center, Department of Chemotherapy
city: Voronezh
country: Russian Federation
facility: Burdenko Voronezh Medical Academy, Oncology Department, Clinical Facility: Regional Clinical Oncology Center
city: Cherkassy
country: Ukraine
facility: Cherkassy Regional Oncology Center, Chemotherapy Department
city: Dnepropetrovsk
country: Ukraine
facility: Dnepropetrovsk State Medical Academy, Oncology Department. Clinical Facility: Dnepropetrovsk City Clinical Hospital #4
city: Donetsk
country: Ukraine
facility: Donetsk State Medical University. Clinical Facility: Donetsk Regional Antineoplastic Center, Mammology Department
city: Ivano-Frankovsk
country: Ukraine
facility: Ivano-Frankovsk State Medical Academy; Oncology Department Clinical Facility: Ivano-Frankovsk Regional Oncology Center
city: Kharkov
country: Ukraine
facility: Kharkov State Medical University. Clinical Facility: Grigoriev Medical Radiology Institute, Chemotherapy Department
city: Kharkov
country: Ukraine
facility: Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department. Clinical Facility: Kharkov Regional Clinical Oncology Dispensary, Chemotherapy Department
city: Kiev
country: Ukraine
facility: Kiev Central Clinical Hospital, Ukraine Security Services, Surgery Department
city: Kiev
country: Ukraine
facility: Kiev Oncology Institute, Ukraine Medical Science Academy, Department of Breast Tumors
city: Kiev
country: Ukraine
facility: Kiev Postgraduate Studies Medical Academy. Clinical Facility: Kiev City Oncology Hospital, Chemotherapy Department
city: Kiev
country: Ukraine
facility: National Medical University, Oncology Department. Clinical Facility: Kiev City Oncology Hospital, Surgery Department
city: Krivoy Rog
country: Ukraine
facility: Krivoy Rog City Oncology Center
city: Lviv
country: Ukraine
facility: Lviv State Medical University, Oncology and Medical Radiology Department. Clinical Facility: Lviv State Oncology Regional Clinical Diagnostic Center, Chemotherapy Department
city: Odessa
country: Ukraine
facility: Odessa State Medical University, Oncology Department. Clinical Facility: Odessa Regional Oncology Center, Chemotherapy Department
city: Uzhgorod
country: Ukraine
facility: Uzhgorod National University Oncology Course of Surgery Department of Postgraduate Education Faculty Clinical Facility: Zakarpatye Regional Oncology Center
city: Zaporozhye
country: Ukraine
facility: Zaporozhye Statue Institute of Postgraduate Training. Oncology Department; Clinical Facility: Zaporozhye Regional Oncology Center
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Paul Goss, M.D.
role: STUDY_CHAIR
References: