Phase III Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer

Breast Neoplasms Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00044291
• Other study ID #: Biomed 777-CLP-29
• Status: Completed
• Phase: Phase 3
• First received: August 23, 2002
• Last updated: July 29, 2015
• Start date: June 2002
• Est. completion date: January 2006

Study information

• Verified date: July 2015
• Source: Intarcia Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 865
• Est. completion date: January 2006
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasms
• Neoplasms, Hormone-Dependent

Intervention

Drug:
• atamestane

• toremifene

• letrozole

• aromatase inhibition

Procedure:
• hormone therapy

• endocrine therapy

• antiestrogen therapy

Locations

Country	Name	City	State
Canada	McGill University, Department of Oncology	Montreal	Quebec
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Northwestern Ontario Regional Cancer Centre	Thunder Bay	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Russian Federation	Arkhangelsk Regional Oncology Center, Department of Chemotherapy	Arkhangelsk
Russian Federation	Tatarstan Republican Clinical Oncology Center	Kazan
Russian Federation	Krasnodar Regional Clinical Oncology Center, Chemotherapy Department	Krasnodar
Russian Federation	Leningrad Regional Oncology Center	Leningrad
Russian Federation	Lipetsk Regional Oncology Center, Department of General Oncology	Lipetsk
Russian Federation	Blokhin Cancer Research Center, Department of Chemotherapy	Moscow
Russian Federation	Blokhin Cancer Research Center, Department of Chemotherapy and Combined Treatment of Tumors	Moscow
Russian Federation	Blokhin Cancer Research Center, Department of Clinical Pharmacology and Chemotherapy	Moscow
Russian Federation	Blokhin Cancer Research Center, Department of New Antitumor Drug Research	Moscow
Russian Federation	Central Clinical Hospital of the Ministry of Transport n.a. Semashko, Department of Chemotherapy	Moscow
Russian Federation	Hertzen Research Institute of Oncology, Department of Chemotherapy	Moscow
Russian Federation	Moscow City Hospital #40, Department of Chemotherapy	Moscow
Russian Federation	Moscow City Oncology Hospital #62	Moscow
Russian Federation	Murmansk Regional Oncology Center	Murmansk
Russian Federation	Municipal Clinical Hospital #1, Department of Breast Tumors, Oncology Department	Novosibirsk
Russian Federation	Medical Radiological Research Center	Obninsk
Russian Federation	Ryazan Regional Clinical Oncology Center	Ryazan
Russian Federation	Samara Regional Oncology Center, Department of Chemotherapy	Samara
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 Breast Cancer	St. Petersburg
Russian Federation	Petrov Research Institute of Oncology, Department of Chemotherapy	St. Petersburg
Russian Federation	St. Petersburg City Oncology Center	St. Petersburg
Russian Federation	Stavropol Regional Oncology Center, Department of Chemotherapy	Stavropol
Russian Federation	Research Institute of Oncology, Tomsk Scientific Center, Siberian Department of the Russian Academy of Medical Sciences, Department of Chemotherapy	Tomsk
Russian Federation	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
Ukraine	Cherkassy Regional Oncology Center, Chemotherapy Department	Cherkassy
Ukraine	Dnepropetrovsk State Medical Academy, Oncology Department. Clinical Facility: Dnepropetrovsk City Clinical Hospital #4	Dnepropetrovsk
Ukraine	Donetsk State Medical University. Clinical Facility: Donetsk Regional Antineoplastic Center, Mammology Department	Donetsk
Ukraine	Ivano-Frankovsk State Medical Academy; Oncology Department Clinical Facility: Ivano-Frankovsk Regional Oncology Center	Ivano-Frankovsk
Ukraine	Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department. Clinical Facility: Kharkov Regional Clinical Oncology Dispensary, Chemotherapy Department	Kharkov
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	Kiev Postgraduate Studies Medical Academy. Clinical Facility: Kiev City Oncology Hospital, Chemotherapy Department	Kiev
Ukraine	National Medical University, Oncology Department. Clinical Facility: Kiev City Oncology Hospital, Surgery Department	Kiev
Ukraine	Krivoy Rog City Oncology Center	Krivoy Rog
Ukraine	Lviv State Medical University, Oncology and Medical Radiology Department. Clinical Facility: Lviv State Oncology Regional Clinical Diagnostic Center, Chemotherapy Department	Lviv
Ukraine	Odessa State Medical University, Oncology Department. Clinical Facility: Odessa Regional Oncology Center, Chemotherapy Department	Odessa
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
United States	Maryland Hematology/Oncology Associates	Baltimore	Maryland
United States	Hematology Oncology Consultants, Inc.	Columbus	Ohio
United States	Great Falls Clinic-Oncology West	Great Falls	Montana
United States	California Cancer Care, Inc.	Greenbrae	California
United States	Oncology Consultants	Houston	Texas
United States	Kansas City Oncology and Hematology Group	Kansas City	Missouri
United States	First Dynamic Healthcare Services, Inc.	Killeen	Texas
United States	Midwest Internal Medicine, PLLC	Lake Havasu City	Arizona
United States	Cache Valley Cancer Treatment & Research Clinic	Logan	Utah
United States	Innovative Medical Research of South Florida Inc.	Miami Shores	Florida
United States	Slocum-Dickson Medical Group	New Hartford	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Western Washington Oncology Inc., P.S.	Olympia	Washington
United States	Sharp Memorial Hospital	San Diego	California
United States	Oncology Care Associates, PLLC	St. Joseph	Michigan
United States	Georgia Cancer Specialists	Tucker	Georgia
United States	Arizona Clinical Research Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Intarcia Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No