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

Primary Purpose

Breast Neoplasms, Neoplasms, Hormone-dependent

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
atamestane
toremifene
letrozole
aromatase inhibition
hormone therapy
endocrine therapy
antiestrogen therapy
Sponsored by
Intarcia Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Neoplasms focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Midwest Internal Medicine, PLLC
  • Arizona Clinical Research Center
  • California Cancer Care, Inc.
  • Sharp Memorial Hospital
  • Innovative Medical Research of South Florida Inc.
  • Georgia Cancer Specialists
  • Maryland Hematology/Oncology Associates
  • Oncology Care Associates, PLLC
  • Kansas City Oncology and Hematology Group
  • Great Falls Clinic-Oncology West
  • Slocum-Dickson Medical Group
  • Hematology Oncology Consultants, Inc.
  • Oncology Consultants
  • First Dynamic Healthcare Services, Inc.
  • Cache Valley Cancer Treatment & Research Clinic
  • Virginia Oncology Associates
  • Western Washington Oncology Inc., P.S.
  • Ottawa Regional Cancer Centre
  • Northwestern Ontario Regional Cancer Centre
  • Princess Margaret Hospital
  • McGill University, Department of Oncology
  • Arkhangelsk Regional Oncology Center, Department of Chemotherapy
  • Tatarstan Republican Clinical Oncology Center
  • Krasnodar Regional Clinical Oncology Center, Chemotherapy Department
  • Leningrad Regional Oncology Center
  • Lipetsk Regional Oncology Center, Department of General Oncology
  • Blokhin Cancer Research Center, Department of Chemotherapy and Combined Treatment of Tumors
  • Blokhin Cancer Research Center, Department of Chemotherapy
  • Blokhin Cancer Research Center, Department of Clinical Pharmacology and Chemotherapy
  • Blokhin Cancer Research Center, Department of New Antitumor Drug Research
  • Hertzen Research Institute of Oncology, Department of Chemotherapy
  • Central Clinical Hospital of the Ministry of Transport n.a. Semashko, Department of Chemotherapy
  • Moscow City Hospital #40, Department of Chemotherapy
  • Moscow City Oncology Hospital #62
  • Murmansk Regional Oncology Center
  • Municipal Clinical Hospital #1, Department of Breast Tumors, Oncology Department
  • Medical Radiological Research Center
  • Ryazan Regional Clinical Oncology Center
  • Samara Regional Oncology Center, Department of Chemotherapy
  • St. Petersburg City Oncology Center
  • Laboratory of Thoracic Oncology, St. Petersburg Pavlov State Medical University, Research Institute of Pulmonology
  • Petrov Research Institute of Oncology, Department of Biotherapy and Bone Marrow Transplantation
  • Petrov Research Institute of Oncology, Department of Breast Cancer
  • Petrov Research Institute of Oncology, Department of Chemotherapy
  • Stavropol Regional Oncology Center, Department of Chemotherapy
  • Research Institute of Oncology, Tomsk Scientific Center, Siberian Department of the Russian Academy of Medical Sciences, Department of Chemotherapy
  • V. Novgorod Regional Oncology Center, Department of Chemotherapy
  • Burdenko Voronezh Medical Academy, Oncology Department, Clinical Facility: Regional Clinical Oncology Center
  • Cherkassy Regional Oncology Center, Chemotherapy Department
  • Dnepropetrovsk State Medical Academy, Oncology Department. Clinical Facility: Dnepropetrovsk City Clinical Hospital #4
  • Donetsk State Medical University. Clinical Facility: Donetsk Regional Antineoplastic Center, Mammology Department
  • Ivano-Frankovsk State Medical Academy; Oncology Department Clinical Facility: Ivano-Frankovsk Regional Oncology Center
  • Kharkov State Medical University. Clinical Facility: Grigoriev Medical Radiology Institute, Chemotherapy Department
  • Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department. Clinical Facility: Kharkov Regional Clinical Oncology Dispensary, Chemotherapy Department
  • Kiev Central Clinical Hospital, Ukraine Security Services, Surgery Department
  • Kiev Oncology Institute, Ukraine Medical Science Academy, Department of Breast Tumors
  • Kiev Postgraduate Studies Medical Academy. Clinical Facility: Kiev City Oncology Hospital, Chemotherapy Department
  • National Medical University, Oncology Department. Clinical Facility: Kiev City Oncology Hospital, Surgery Department
  • Krivoy Rog City Oncology Center
  • Lviv State Medical University, Oncology and Medical Radiology Department. Clinical Facility: Lviv State Oncology Regional Clinical Diagnostic Center, Chemotherapy Department
  • Odessa State Medical University, Oncology Department. Clinical Facility: Odessa Regional Oncology Center, Chemotherapy Department
  • Uzhgorod National University Oncology Course of Surgery Department of Postgraduate Education Faculty Clinical Facility: Zakarpatye Regional Oncology Center
  • Zaporozhye Statue Institute of Postgraduate Training. Oncology Department; Clinical Facility: Zaporozhye Regional Oncology Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Atamestane + toremifene

Letrozole + placebo

Arm Description

Outcomes

Primary Outcome Measures

Time to tumor progression

Secondary Outcome Measures

Full Information

First Posted
August 23, 2002
Last Updated
July 29, 2015
Sponsor
Intarcia Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT00044291
Brief Title
Phase III Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
June 2002 (undefined)
Primary Completion Date
January 2006 (Actual)
Study Completion Date
January 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Intarcia Therapeutics

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
865 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Atamestane + toremifene
Arm Type
Experimental
Arm Title
Letrozole + placebo
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
atamestane
Intervention Type
Drug
Intervention Name(s)
toremifene
Intervention Type
Drug
Intervention Name(s)
letrozole
Intervention Type
Drug
Intervention Name(s)
aromatase inhibition
Intervention Type
Procedure
Intervention Name(s)
hormone therapy
Intervention Type
Procedure
Intervention Name(s)
endocrine therapy
Intervention Type
Procedure
Intervention Name(s)
antiestrogen therapy
Primary Outcome Measure Information:
Title
Time to tumor progression
Time Frame
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Goss, M.D.
Organizational Affiliation
Princess Margaret Hospital, Canada
Official's Role
Study Chair
Facility Information:
Facility Name
Midwest Internal Medicine, PLLC
City
Lake Havasu City
State/Province
Arizona
ZIP/Postal Code
86403
Country
United States
Facility Name
Arizona Clinical Research Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85712
Country
United States
Facility Name
California Cancer Care, Inc.
City
Greenbrae
State/Province
California
ZIP/Postal Code
94904-2007
Country
United States
Facility Name
Sharp Memorial Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Innovative Medical Research of South Florida Inc.
City
Miami Shores
State/Province
Florida
ZIP/Postal Code
33138
Country
United States
Facility Name
Georgia Cancer Specialists
City
Tucker
State/Province
Georgia
ZIP/Postal Code
30084
Country
United States
Facility Name
Maryland Hematology/Oncology Associates
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21236
Country
United States
Facility Name
Oncology Care Associates, PLLC
City
St. Joseph
State/Province
Michigan
ZIP/Postal Code
49085
Country
United States
Facility Name
Kansas City Oncology and Hematology Group
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
Great Falls Clinic-Oncology West
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
Facility Name
Slocum-Dickson Medical Group
City
New Hartford
State/Province
New York
ZIP/Postal Code
13413
Country
United States
Facility Name
Hematology Oncology Consultants, Inc.
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Facility Name
Oncology Consultants
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
First Dynamic Healthcare Services, Inc.
City
Killeen
State/Province
Texas
ZIP/Postal Code
76710
Country
United States
Facility Name
Cache Valley Cancer Treatment & Research Clinic
City
Logan
State/Province
Utah
ZIP/Postal Code
84341
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
Western Washington Oncology Inc., P.S.
City
Olympia
State/Province
Washington
ZIP/Postal Code
98502
Country
United States
Facility Name
Ottawa Regional Cancer Centre
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K 1H 1C4
Country
Canada
Facility Name
Northwestern Ontario Regional Cancer Centre
City
Thunder Bay
State/Province
Ontario
ZIP/Postal Code
P7A7T1
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
McGill University, Department of Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W1S6
Country
Canada
Facility Name
Arkhangelsk Regional Oncology Center, Department of Chemotherapy
City
Arkhangelsk
ZIP/Postal Code
163045
Country
Russian Federation
Facility Name
Tatarstan Republican Clinical Oncology Center
City
Kazan
ZIP/Postal Code
420029
Country
Russian Federation
Facility Name
Krasnodar Regional Clinical Oncology Center, Chemotherapy Department
City
Krasnodar
ZIP/Postal Code
350040
Country
Russian Federation
Facility Name
Leningrad Regional Oncology Center
City
Leningrad
ZIP/Postal Code
188663
Country
Russian Federation
Facility Name
Lipetsk Regional Oncology Center, Department of General Oncology
City
Lipetsk
ZIP/Postal Code
398005
Country
Russian Federation
Facility Name
Blokhin Cancer Research Center, Department of Chemotherapy and Combined Treatment of Tumors
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Blokhin Cancer Research Center, Department of Chemotherapy
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Blokhin Cancer Research Center, Department of Clinical Pharmacology and Chemotherapy
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Blokhin Cancer Research Center, Department of New Antitumor Drug Research
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Hertzen Research Institute of Oncology, Department of Chemotherapy
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Facility Name
Central Clinical Hospital of the Ministry of Transport n.a. Semashko, Department of Chemotherapy
City
Moscow
ZIP/Postal Code
129128
Country
Russian Federation
Facility Name
Moscow City Hospital #40, Department of Chemotherapy
City
Moscow
ZIP/Postal Code
129301
Country
Russian Federation
Facility Name
Moscow City Oncology Hospital #62
City
Moscow
ZIP/Postal Code
143423
Country
Russian Federation
Facility Name
Murmansk Regional Oncology Center
City
Murmansk
ZIP/Postal Code
183047
Country
Russian Federation
Facility Name
Municipal Clinical Hospital #1, Department of Breast Tumors, Oncology Department
City
Novosibirsk
ZIP/Postal Code
630047
Country
Russian Federation
Facility Name
Medical Radiological Research Center
City
Obninsk
ZIP/Postal Code
249036
Country
Russian Federation
Facility Name
Ryazan Regional Clinical Oncology Center
City
Ryazan
ZIP/Postal Code
390046
Country
Russian Federation
Facility Name
Samara Regional Oncology Center, Department of Chemotherapy
City
Samara
ZIP/Postal Code
443066
Country
Russian Federation
Facility Name
St. Petersburg City Oncology Center
City
St. Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Laboratory of Thoracic Oncology, St. Petersburg Pavlov State Medical University, Research Institute of Pulmonology
City
St. Petersburg
ZIP/Postal Code
197089
Country
Russian Federation
Facility Name
Petrov Research Institute of Oncology, Department of Biotherapy and Bone Marrow Transplantation
City
St. Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
Petrov Research Institute of Oncology, Department of Breast Cancer
City
St. Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
Petrov Research Institute of Oncology, Department of Chemotherapy
City
St. Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
Stavropol Regional Oncology Center, Department of Chemotherapy
City
Stavropol
ZIP/Postal Code
355018
Country
Russian Federation
Facility Name
Research Institute of Oncology, Tomsk Scientific Center, Siberian Department of the Russian Academy of Medical Sciences, Department of Chemotherapy
City
Tomsk
ZIP/Postal Code
634028
Country
Russian Federation
Facility Name
V. Novgorod Regional Oncology Center, Department of Chemotherapy
City
V. Novgorod
ZIP/Postal Code
173016
Country
Russian Federation
Facility Name
Burdenko Voronezh Medical Academy, Oncology Department, Clinical Facility: Regional Clinical Oncology Center
City
Voronezh
ZIP/Postal Code
394000
Country
Russian Federation
Facility Name
Cherkassy Regional Oncology Center, Chemotherapy Department
City
Cherkassy
ZIP/Postal Code
18009
Country
Ukraine
Facility Name
Dnepropetrovsk State Medical Academy, Oncology Department. Clinical Facility: Dnepropetrovsk City Clinical Hospital #4
City
Dnepropetrovsk
ZIP/Postal Code
49102
Country
Ukraine
Facility Name
Donetsk State Medical University. Clinical Facility: Donetsk Regional Antineoplastic Center, Mammology Department
City
Donetsk
ZIP/Postal Code
83092
Country
Ukraine
Facility Name
Ivano-Frankovsk State Medical Academy; Oncology Department Clinical Facility: Ivano-Frankovsk Regional Oncology Center
City
Ivano-Frankovsk
ZIP/Postal Code
76000
Country
Ukraine
Facility Name
Kharkov State Medical University. Clinical Facility: Grigoriev Medical Radiology Institute, Chemotherapy Department
City
Kharkov
ZIP/Postal Code
61024
Country
Ukraine
Facility Name
Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department. Clinical Facility: Kharkov Regional Clinical Oncology Dispensary, Chemotherapy Department
City
Kharkov
ZIP/Postal Code
61070
Country
Ukraine
Facility Name
Kiev Central Clinical Hospital, Ukraine Security Services, Surgery Department
City
Kiev
ZIP/Postal Code
01021
Country
Ukraine
Facility Name
Kiev Oncology Institute, Ukraine Medical Science Academy, Department of Breast Tumors
City
Kiev
ZIP/Postal Code
03022
Country
Ukraine
Facility Name
Kiev Postgraduate Studies Medical Academy. Clinical Facility: Kiev City Oncology Hospital, Chemotherapy Department
City
Kiev
ZIP/Postal Code
03115
Country
Ukraine
Facility Name
National Medical University, Oncology Department. Clinical Facility: Kiev City Oncology Hospital, Surgery Department
City
Kiev
ZIP/Postal Code
03115
Country
Ukraine
Facility Name
Krivoy Rog City Oncology Center
City
Krivoy Rog
ZIP/Postal Code
50048
Country
Ukraine
Facility Name
Lviv State Medical University, Oncology and Medical Radiology Department. Clinical Facility: Lviv State Oncology Regional Clinical Diagnostic Center, Chemotherapy Department
City
Lviv
ZIP/Postal Code
79031
Country
Ukraine
Facility Name
Odessa State Medical University, Oncology Department. Clinical Facility: Odessa Regional Oncology Center, Chemotherapy Department
City
Odessa
ZIP/Postal Code
65055
Country
Ukraine
Facility Name
Uzhgorod National University Oncology Course of Surgery Department of Postgraduate Education Faculty Clinical Facility: Zakarpatye Regional Oncology Center
City
Uzhgorod
ZIP/Postal Code
88000
Country
Ukraine
Facility Name
Zaporozhye Statue Institute of Postgraduate Training. Oncology Department; Clinical Facility: Zaporozhye Regional Oncology Center
City
Zaporozhye
ZIP/Postal Code
69104
Country
Ukraine

12. IPD Sharing Statement

Learn more about this trial

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

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