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

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.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms; Neoplasms, Hormone-dependent
• Intervention / Treatment: Drug: atamestane; Drug: toremifene; Drug: aromatase inhibition; Procedure: hormone therapy; Procedure: endocrine therapy; Procedure: antiestrogen therapy; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 865
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K 1H 1C4
      • Ottawa Regional Cancer Centre
    • Thunder Bay, Ontario, Canada, P7A7T1
      • Northwestern Ontario Regional Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2W1S6
      • McGill University, Department of Oncology
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Arkhangelsk Regional Oncology Center, Department of Chemotherapy
  • Kazan, Russian Federation, 420029
    • Tatarstan Republican Clinical Oncology Center
  • Krasnodar, Russian Federation, 350040
    • Krasnodar Regional Clinical Oncology Center, Chemotherapy Department
  • Leningrad, Russian Federation, 188663
    • Leningrad Regional Oncology Center
  • Lipetsk, Russian Federation, 398005
    • Lipetsk Regional Oncology Center, Department of General Oncology
  • Moscow, Russian Federation, 115478
    • Blokhin Cancer Research Center, Department of Chemotherapy and Combined Treatment of Tumors
  • Moscow, Russian Federation, 115478
    • Blokhin Cancer Research Center, Department of Chemotherapy
  • Moscow, Russian Federation, 115478
    • Blokhin Cancer Research Center, Department of Clinical Pharmacology and Chemotherapy
  • Moscow, Russian Federation, 115478
    • Blokhin Cancer Research Center, Department of New Antitumor Drug Research
  • Moscow, Russian Federation, 125284
    • Hertzen Research Institute of Oncology, Department of Chemotherapy
  • Moscow, Russian Federation, 129128
    • Central Clinical Hospital of the Ministry of Transport n.a. Semashko, Department of Chemotherapy
  • Moscow, Russian Federation, 129301
    • Moscow City Hospital #40, Department of Chemotherapy
  • Moscow, Russian Federation, 143423
    • Moscow City Oncology Hospital #62
  • Murmansk, Russian Federation, 183047
    • Murmansk Regional Oncology Center
  • Novosibirsk, Russian Federation, 630047
    • Municipal Clinical Hospital #1, Department of Breast Tumors, Oncology Department
  • Obninsk, Russian Federation, 249036
    • Medical Radiological Research Center
  • Ryazan, Russian Federation, 390046
    • Ryazan Regional Clinical Oncology Center
  • Samara, Russian Federation, 443066
    • Samara Regional Oncology Center, Department of Chemotherapy
  • St. Petersburg, Russian Federation, 197022
    • St. Petersburg City Oncology Center
  • St. Petersburg, Russian Federation, 197089
    • Laboratory of Thoracic Oncology, St. Petersburg Pavlov State Medical University, Research Institute of Pulmonology
  • St. Petersburg, Russian Federation, 197758
    • Petrov Research Institute of Oncology, Department of Biotherapy and Bone Marrow Transplantation
  • St. Petersburg, Russian Federation, 197758
    • Petrov Research Institute of Oncology, Department of Breast Cancer
  • St. Petersburg, Russian Federation, 197758
    • Petrov Research Institute of Oncology, Department of Chemotherapy
  • Stavropol, Russian Federation, 355018
    • Stavropol Regional Oncology Center, Department of Chemotherapy
  • Tomsk, Russian Federation, 634028
    • Research Institute of Oncology, Tomsk Scientific Center, Siberian Department of the Russian Academy of Medical Sciences, Department of Chemotherapy
  • V. Novgorod, Russian Federation, 173016
    • V. Novgorod Regional Oncology Center, Department of Chemotherapy
  • Voronezh, Russian Federation, 394000
    • Burdenko Voronezh Medical Academy, Oncology Department, Clinical Facility: Regional Clinical Oncology Center
• Ukraine
  • Cherkassy, Ukraine, 18009
    • Cherkassy Regional Oncology Center, Chemotherapy Department
  • Dnepropetrovsk, Ukraine, 49102
    • Dnepropetrovsk State Medical Academy, Oncology Department. Clinical Facility: Dnepropetrovsk City Clinical Hospital #4
  • Donetsk, Ukraine, 83092
    • Donetsk State Medical University. Clinical Facility: Donetsk Regional Antineoplastic Center, Mammology Department
  • Ivano-Frankovsk, Ukraine, 76000
    • Ivano-Frankovsk State Medical Academy; Oncology Department Clinical Facility: Ivano-Frankovsk Regional Oncology Center
  • Kharkov, Ukraine, 61024
    • Kharkov State Medical University. Clinical Facility: Grigoriev Medical Radiology Institute, Chemotherapy Department
  • Kharkov, Ukraine, 61070
    • Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department. Clinical Facility: Kharkov Regional Clinical Oncology Dispensary, Chemotherapy Department
  • Kiev, Ukraine, 01021
    • Kiev Central Clinical Hospital, Ukraine Security Services, Surgery Department
  • Kiev, Ukraine, 03022
    • Kiev Oncology Institute, Ukraine Medical Science Academy, Department of Breast Tumors
  • Kiev, Ukraine, 03115
    • Kiev Postgraduate Studies Medical Academy. Clinical Facility: Kiev City Oncology Hospital, Chemotherapy Department
  • Kiev, Ukraine, 03115
    • National Medical University, Oncology Department. Clinical Facility: Kiev City Oncology Hospital, Surgery Department
  • Krivoy Rog, Ukraine, 50048
    • Krivoy Rog City Oncology Center
  • Lviv, Ukraine, 79031
    • Lviv State Medical University, Oncology and Medical Radiology Department. Clinical Facility: Lviv State Oncology Regional Clinical Diagnostic Center, Chemotherapy Department
  • Odessa, Ukraine, 65055
    • Odessa State Medical University, Oncology Department. Clinical Facility: Odessa Regional Oncology Center, Chemotherapy Department
  • Uzhgorod, Ukraine, 88000
    • Uzhgorod National University Oncology Course of Surgery Department of Postgraduate Education Faculty Clinical Facility: Zakarpatye Regional Oncology Center
  • Zaporozhye, Ukraine, 69104
    • Zaporozhye Statue Institute of Postgraduate Training. Oncology Department; Clinical Facility: Zaporozhye Regional Oncology Center
• United States
  • Arizona
    • Lake Havasu City, Arizona, United States, 86403
      • Midwest Internal Medicine, PLLC
    • Tucson, Arizona, United States, 85712
      • Arizona Clinical Research Center
  • California
    • Greenbrae, California, United States, 94904-2007
      • California Cancer Care, Inc.
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
  • Florida
    • Miami Shores, Florida, United States, 33138
      • Innovative Medical Research of South Florida Inc.
  • Georgia
    • Tucker, Georgia, United States, 30084
      • Georgia Cancer Specialists
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • Maryland Hematology/Oncology Associates
  • Michigan
    • St. Joseph, Michigan, United States, 49085
      • Oncology Care Associates, PLLC
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Oncology and Hematology Group
  • Montana
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic-Oncology West
  • New York
    • New Hartford, New York, United States, 13413
      • Slocum-Dickson Medical Group
  • Ohio
    • Columbus, Ohio, United States, 43235
      • Hematology Oncology Consultants, Inc.
  • Texas
    • Houston, Texas, United States, 77024
      • Oncology Consultants
    • Killeen, Texas, United States, 76710
      • First Dynamic Healthcare Services, Inc.
  • Utah
    • Logan, Utah, United States, 84341
      • Cache Valley Cancer Treatment & Research Clinic
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
  • Washington
    • Olympia, Washington, United States, 98502
      • Western Washington Oncology Inc., P.S.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atamestane + toremifene	Drug: atamestane; Drug: toremifene; Drug: aromatase inhibition; Procedure: hormone therapy; Procedure: endocrine therapy; Procedure: antiestrogen therapy
Active Comparator: Letrozole + placebo	Drug: aromatase inhibition; Procedure: hormone therapy; Procedure: endocrine therapy; Drug: letrozole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Intarcia Therapeutics
• Investigators: Study Chair: Paul Goss, M.D., Princess Margaret Hospital, Canada

Study record dates

Study Major Dates

• Study Start: June 1, 2002
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: August 23, 2002
• First Submitted That Met QC Criteria: August 26, 2002
• First Posted (Estimate): August 27, 2002

Study Record Updates

• Last Update Posted (Estimate): July 31, 2015
• Last Update Submitted That Met QC Criteria: July 29, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: stage IV breast cancer; stage IIIA breast cancer; recurrent breast cancer; stage IIIB breast cancer; Metastatic breast cancer; ductal breast carcinoma; Atamestane; Toremifene; Letrozole; Aromatase inhibitor; Receptor-positive; First line therapy; Estrogen blocker; Locally advanced breast cancer; Locally recurrent breast cancer; lobular breast carcinoma
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplasms; Breast Neoplasms; Neoplasms, Hormone-Dependent; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Selective Estrogen Receptor Modulators; Letrozole; Hormones; Toremifene; Atamestane; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogen Receptor Antagonists
• Other Study ID Numbers: Biomed 777-CLP-29