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

NCT ID: NCT00044291

Last Updated: 2015-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

865 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-06-30

Study Completion Date

2006-01-31

Brief Summary

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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

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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.

Conditions

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Breast Neoplasms Neoplasms, Hormone-dependent

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Atamestane + toremifene

Group Type EXPERIMENTAL

atamestane

Intervention Type DRUG

toremifene

Intervention Type DRUG

aromatase inhibition

Intervention Type DRUG

hormone therapy

Intervention Type PROCEDURE

endocrine therapy

Intervention Type PROCEDURE

antiestrogen therapy

Intervention Type PROCEDURE

Letrozole + placebo

Group Type ACTIVE_COMPARATOR

letrozole

Intervention Type DRUG

aromatase inhibition

Intervention Type DRUG

hormone therapy

Intervention Type PROCEDURE

endocrine therapy

Intervention Type PROCEDURE

Interventions

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atamestane

Intervention Type DRUG

toremifene

Intervention Type DRUG

letrozole

Intervention Type DRUG

aromatase inhibition

Intervention Type DRUG

hormone therapy

Intervention Type PROCEDURE

endocrine therapy

Intervention Type PROCEDURE

antiestrogen therapy

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Intarcia Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul Goss, M.D.

Role: STUDY_CHAIR

Princess Margaret Hospital, Canada

Locations

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Midwest Internal Medicine, PLLC

Lake Havasu City, Arizona, United States

Site Status

Arizona Clinical Research Center

Tucson, Arizona, United States

Site Status

California Cancer Care, Inc.

Greenbrae, California, United States

Site Status

Sharp Memorial Hospital

San Diego, California, United States

Site Status

Innovative Medical Research of South Florida Inc.

Miami Shores, Florida, United States

Site Status

Georgia Cancer Specialists

Tucker, Georgia, United States

Site Status

Maryland Hematology/Oncology Associates

Baltimore, Maryland, United States

Site Status

Oncology Care Associates, PLLC

Saint Joseph, Michigan, United States

Site Status

Kansas City Oncology and Hematology Group

Kansas City, Missouri, United States

Site Status

Great Falls Clinic-Oncology West

Great Falls, Montana, United States

Site Status

Slocum-Dickson Medical Group

New Hartford, New York, United States

Site Status

Hematology Oncology Consultants, Inc.

Columbus, Ohio, United States

Site Status

Oncology Consultants

Houston, Texas, United States

Site Status

First Dynamic Healthcare Services, Inc.

Killeen, Texas, United States

Site Status

Cache Valley Cancer Treatment & Research Clinic

Logan, Utah, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Western Washington Oncology Inc., P.S.

Olympia, Washington, United States

Site Status

Ottawa Regional Cancer Centre

Ottawa, Ontario, Canada

Site Status

Northwestern Ontario Regional Cancer Centre

Thunder Bay, Ontario, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

McGill University, Department of Oncology

Montreal, Quebec, Canada

Site Status

Arkhangelsk Regional Oncology Center, Department of Chemotherapy

Arkhangelsk, , Russia

Site Status

Tatarstan Republican Clinical Oncology Center

Kazan', , Russia

Site Status

Krasnodar Regional Clinical Oncology Center, Chemotherapy Department

Krasnodar, , Russia

Site Status

Lipetsk Regional Oncology Center, Department of General Oncology

Lipetsk, , Russia

Site Status

Blokhin Cancer Research Center, Department of Chemotherapy and Combined Treatment of Tumors

Moscow, , Russia

Site Status

Blokhin Cancer Research Center, Department of Chemotherapy

Moscow, , Russia

Site Status

Blokhin Cancer Research Center, Department of Clinical Pharmacology and Chemotherapy

Moscow, , Russia

Site Status

Blokhin Cancer Research Center, Department of New Antitumor Drug Research

Moscow, , Russia

Site Status

Hertzen Research Institute of Oncology, Department of Chemotherapy

Moscow, , Russia

Site Status

Central Clinical Hospital of the Ministry of Transport n.a. Semashko, Department of Chemotherapy

Moscow, , Russia

Site Status

Moscow City Hospital #40, Department of Chemotherapy

Moscow, , Russia

Site Status

Moscow City Oncology Hospital #62

Moscow, , Russia

Site Status

Murmansk Regional Oncology Center

Murmansk, , Russia

Site Status

Municipal Clinical Hospital #1, Department of Breast Tumors, Oncology Department

Novosibirsk, , Russia

Site Status

Medical Radiological Research Center

Obninsk, , Russia

Site Status

Ryazan Regional Clinical Oncology Center

Ryazan, , Russia

Site Status

Leningrad Regional Oncology Center

Saint Petersburg, , Russia

Site Status

St. Petersburg City Oncology Center

Saint Petersburg, , Russia

Site Status

Laboratory of Thoracic Oncology, St. Petersburg Pavlov State Medical University, Research Institute of Pulmonology

Saint Petersburg, , Russia

Site Status

Petrov Research Institute of Oncology, Department of Biotherapy and Bone Marrow Transplantation

Saint Petersburg, , Russia

Site Status

Petrov Research Institute of Oncology, Department of Breast Cancer

Saint Petersburg, , Russia

Site Status

Petrov Research Institute of Oncology, Department of Chemotherapy

Saint Petersburg, , Russia

Site Status

Samara Regional Oncology Center, Department of Chemotherapy

Samara, , Russia

Site Status

Stavropol Regional Oncology Center, Department of Chemotherapy

Stavropol, , Russia

Site Status

Research Institute of Oncology, Tomsk Scientific Center, Siberian Department of the Russian Academy of Medical Sciences, Department of Chemotherapy

Tomsk, , Russia

Site Status

V. Novgorod Regional Oncology Center, Department of Chemotherapy

V. Novgorod, , Russia

Site Status

Burdenko Voronezh Medical Academy, Oncology Department, Clinical Facility: Regional Clinical Oncology Center

Voronezh, , Russia

Site Status

Cherkassy Regional Oncology Center, Chemotherapy Department

Cherkassy, , Ukraine

Site Status

Dnepropetrovsk State Medical Academy, Oncology Department. Clinical Facility: Dnepropetrovsk City Clinical Hospital #4

Dnipro, , Ukraine

Site Status

Donetsk State Medical University. Clinical Facility: Donetsk Regional Antineoplastic Center, Mammology Department

Donetsk, , Ukraine

Site Status

Ivano-Frankovsk State Medical Academy; Oncology Department Clinical Facility: Ivano-Frankovsk Regional Oncology Center

Ivano-Frankivsk, , Ukraine

Site Status

Kharkov State Medical University. Clinical Facility: Grigoriev Medical Radiology Institute, Chemotherapy Department

Kharkiv, , Ukraine

Site Status

Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department. Clinical Facility: Kharkov Regional Clinical Oncology Dispensary, Chemotherapy Department

Kharkiv, , Ukraine

Site Status

Kiev Central Clinical Hospital, Ukraine Security Services, Surgery Department

Kiev, , Ukraine

Site Status

Kiev Oncology Institute, Ukraine Medical Science Academy, Department of Breast Tumors

Kiev, , Ukraine

Site Status

Kiev Postgraduate Studies Medical Academy. Clinical Facility: Kiev City Oncology Hospital, Chemotherapy Department

Kiev, , Ukraine

Site Status

National Medical University, Oncology Department. Clinical Facility: Kiev City Oncology Hospital, Surgery Department

Kiev, , Ukraine

Site Status

Krivoy Rog City Oncology Center

Kryvyi Rih, , Ukraine

Site Status

Lviv State Medical University, Oncology and Medical Radiology Department. Clinical Facility: Lviv State Oncology Regional Clinical Diagnostic Center, Chemotherapy Department

Lviv, , Ukraine

Site Status

Odessa State Medical University, Oncology Department. Clinical Facility: Odessa Regional Oncology Center, Chemotherapy Department

Odesa, , Ukraine

Site Status

Uzhgorod National University Oncology Course of Surgery Department of Postgraduate Education Faculty Clinical Facility: Zakarpatye Regional Oncology Center

Uzhhorod, , Ukraine

Site Status

Zaporozhye Statue Institute of Postgraduate Training. Oncology Department; Clinical Facility: Zaporozhye Regional Oncology Center

Zaporizhzhya, , Ukraine

Site Status

Countries

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United States Canada Russia Ukraine

Other Identifiers

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Biomed 777-CLP-29

Identifier Type: -

Identifier Source: org_study_id

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