The CAT Study: Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer

Phase 3 Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer

The purpose of this study is to determine whether maximal estrogen suppression achieved via the combination 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, and whether the side effects of the combined hormonal therapy are different from the side effects of letrozole.

Study Overview

• Status: Terminated
• Conditions: Breast Neoplasms; Neoplasms, Hormone-Dependent
• Intervention / Treatment: Drug: Letrozole; Drug: Toremifene; Drug: Atamestane; Drug: Aromatase inhibition; Drug: Estrogen receptor blocker; Procedure: Hormone therapy; Procedure: Endocrine therapy; Procedure: Antiestrogen therapy

Detailed Description

Aromatase is an enzyme expressed in tissues such as muscle and fat in postmenopausal women. These non-ovarian tissues become the dominant sources of estrogen in postmenopausal women. Breast cancer cells are often very dependent on estrogens to continue to grow. Atamestane blocks the formation of estrogens from androgenic precursors in the body via the aromatase enzyme. 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 complete suppression of estrogen stimulation of breast cancer cells. This study is designed to determine whether combined hormonal therapy will lengthen the time to disease progression and the rate of objective response, as compared to single agent therapy with the approved aromatase inhibitor letrozole.

• Study Type: Interventional
• Enrollment: 842
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • Research Site
  • Plovdiv, Bulgaria, 4004
    • Research Site
  • Shumen, Bulgaria, 9700
    • Research Site
  • Sofia, Bulgaria, 1233
    • Research Site
  • Sofia, Bulgaria, 1756
    • Research Site
  • Stara Zagora, Bulgaria, 6003
    • Research Site
  • Varna, Bulgaria, 9010
    • Research Site
• Romania
  • Arad, Romania, 310017
    • Research Site
  • Brasov, Romania, 500366
    • Research Site
  • Bucharest, Romania, 22328
    • Research Site
  • Bucharest, Romania, 22115
    • Research Site
  • Cluj-Napoca, Romania, 400015
    • Research Site
  • Oradea, Romania, 410032
    • Research Site
  • Ploiesti, Romania, 100337
    • Research Site
  • Targu-Mures, Romania, 540141
    • Research Site
  • Timisoara, Romania, 300223
    • Research Site
• Russian Federation
  • Arkhanglsk, Russian Federation, 163045
    • Research Site
  • Astrakhan, Russian Federation, 414041
    • Research Site
  • Chelyabinsk, Russian Federation, 454087
    • Research Site
  • Engels, Russian Federation, 413115
    • Research Site
  • Irkutsk, Russian Federation, 664035
    • Research Site
  • Kaliningrad, Russian Federation, 236040
    • Research Site
  • Kaluga, Russian Federation, 248007
    • Research Site
  • Kazan, Russian Federation, 420012
    • Research Site
  • Krasnodar, Russian Federation, 350040
    • Research Site
  • Moscow, Russian Federation, 121356
    • Research Site
  • Moscow, Russian Federation, 119121
    • Research Site
  • Omsk, Russian Federation, 644013
    • Research Site
  • Orel, Russian Federation, 302020
    • Research Site
  • Orenburg, Russian Federation, 460021
    • Research Site
  • Perm, Russian Federation, 614066
    • Research Site
  • Pyatigorsk, Russian Federation, 357524
    • Research Site
  • Sochi, Russian Federation, 354057
    • Research Site
  • St. Petersburg, Russian Federation, 197022
    • Research Site
  • St. Petersburg, Russian Federation, 197758
    • Research Site
  • St. Petersburg, Russian Federation, 191104
    • Research Site
  • Syktyvkar, Russian Federation, 167904
    • Research Site
  • Tambov, Russian Federation, 392013
    • Research Site
  • Ufa, Russian Federation, 450054
    • Research Site
  • Ulyanovsk, Russian Federation, 432063
    • Research Site
  • Yaroslavl, Russian Federation, 150054
    • Research Site
• Ukraine
  • Chernigov, Ukraine, 14029
    • Research Site
  • Chernivtsy, Ukraine, 58013
    • Research Site
  • Donetsk, Ukraine, 83092
    • Research Site
  • Kharkov, Ukraine, 61024
    • Research Site
  • Kherson, Ukraine, 73000
    • Research Site
  • Khmelnitsky, Ukraine, 29009
    • Research Site
  • Lugansk, Ukraine, 91047
    • Research Site
  • Lutsk, Ukraine, 43018
    • Research Site
  • Lviv, Ukraine, 79031
    • Research Site
  • Mariupol, Ukraine, 87500
    • Research Site
  • Odessa, Ukraine, 65025
    • Research Site
  • Sumy, Ukraine, 40005
    • Research Site
  • Ternopil, Ukraine, 46023
    • Research Site
  • Vinnitsa, Ukraine, 21021
    • Research Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36607
      • Research Site
  • Arizona
    • Tuscon, Arizona, United States, 85704
      • Research Site
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Research Site
  • California
    • Fountain Valley, California, United States, 92708
      • Research Site
    • Greenbrae, California, United States, 94904
      • Research Site
    • Los Angeles, California, United States, 90807
      • Research Site
    • Poway, California, United States, 92064
      • Research Site
  • Connecticut
    • Greenwich, Connecticut, United States, 06830
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Research Site
    • Kissimmee, Florida, United States, 34741
      • Research Site
    • Miami, Florida, United States, 33176
      • Research Site
    • Ocala, Florida, United States, 34474
      • Research Site
    • Pembroke Pines, Florida, United States, 33028
      • Research Site
    • Tampa, Florida, United States, 33607
      • Research Site
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Research Site
    • Savannah, Georgia, United States, 31405
      • Research Site
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Research Site
    • New Albany, Indiana, United States, 47150
      • Research Site
  • Kansas
    • Lenexa, Kansas, United States, 66214
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Research Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71105
      • Research Site
  • Maryland
    • Towson, Maryland, United States, 21204
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48076
      • Research Site
    • Flint, Michigan, United States, 48532
      • Research Site
  • Minnesota
    • Robbinsdale, Minnesota, United States, 55422
      • Research Site
  • Missouri
    • St. Louis, Missouri, United States, 63128
      • Research Site
  • Montana
    • Billings, Montana, United States, 59101
      • Research Site
  • Nevada
    • Reno, Nevada, United States, 89502
      • Research Site
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08003
      • Research Site
    • Newark, New Jersey, United States, 07101
      • Research Site
  • New York
    • Fresh Meadows, New York, United States, 11365
      • Research Site
    • Valhalla, New York, United States, 10595
      • Research Site
  • Ohio
    • Wooster, Ohio, United States, 44691
      • Research Site
    • Zanesville, Ohio, United States, 43701
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • Research Site
    • West Reading, Pennsylvania, United States, 19611
      • Research Site
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Research Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Research Site
    • Memphis, Tennessee, United States, 38120
      • Research Site
  • Texas
    • Houston, Texas, United States, 77024
      • Research Site
    • Pasadena, Texas, United States, 77504
      • Research Site
  • Utah
    • Ogden, Utah, United States, 84403
      • Research Site
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Research Site
    • Danville, Virginia, United States, 24541
      • Research Site
    • Norfolk, Virginia, United States, 23502
      • Research Site
  • Washington
    • Lacey, Washington, United States, 98503
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Research Site
    • Racine, Wisconsin, United States, 53405
      • Research Site
    • Rhinelander, Wisconsin, United States, 54501
      • Research Site

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
• Postmenopausal women who are to receive their first hormonal treatment for locally recurrent, locally advanced, or metastatic disease, and who would be appropriate candidates for treatment with antiestrogens or aromatase inhibitors.
• Locally recurrent, locally advanced, locally metastatic disease not amenable to radiation therapy or surgery and/or distant metastatic disease.
• Pathological or histological confirmation at primary diagnosis of breast cancer or at the time of diagnosis of advanced disease.
• 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.

• At least one tumor localization measurable in 2 dimensions.

  • One diameter either at least 2 cm or at least two times the CT/MRI slice/reconstruction thickness for bone/soft tissue/visceral disease assessed by CT/MRI scan (to include spiral CT technique).
  • One diameter at least 2 cm for lesions other than bone lesions assessed by conventional X-ray techniques.
  • 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 primary diagnosis or determined during subsequent biopsy/surgery of metastases.
• Administration of bisphosphonates in patients with bone metastases is allowed, as long as the drug is started prior to randomization of the patient.
• Written informed consent obtained.

Exclusion Criteria:

• Prior hormonal therapy (including oophorectomy or treatment with LH/RH analogs) to treat locally recurrent, locally advanced, or metastatic disease.
• Prior chemotherapy to treat locally recurrent, locally advanced, or metastatic disease.
• Prior adjuvant therapy with aromatase inhibitors or antiestrogens/SERMs with last dose administered within 3 months prior to enrollment.
• Primary diagnosis of disease or progression of disease during therapy with antiestrogens (including SERMs administered for prevention of osteoporosis).
• Life-threatening disease requiring chemotherapeutic intervention.
• 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, contralateral breast cancer, 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 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 as stated in the investigators brochure or product package insert.
• Patients who are unable to comply with the study requirements or diagnostic procedures.
• Prior enrollment in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time to progression

Secondary Outcome Measures

Outcome Measure
Response rate
Overall survival
Safety

Collaborators and Investigators

• Sponsor: Intarcia Therapeutics
• Investigators: Study Chair: Edith Perez, MD, Professor of Medicine, Mayo Clinic, Jacksonville, Florida

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Study Completion: August 1, 2006

Study Registration Dates

• First Submitted: November 22, 2004
• First Submitted That Met QC Criteria: November 22, 2004
• First Posted (ESTIMATE): November 23, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): August 23, 2007
• Last Update Submitted That Met QC Criteria: August 21, 2007
• Last Verified: August 1, 2007

More Information

Terms related to this study

• Keywords: Metastatic breast cancer; Atamestane; Toremifene; Letrozole; Aromatase inhibitor; Receptor-positive; First line therapy; Estrogen blocker; Locally advanced breast cancer; Locally recurrent breast cancer; Breast neoplasms; Stage IV breast cancer; Combined hormonal therapy; Complete estrogen blockade; Ductal breast carcinoma; Fareston®; Femara®; Lobular breast carcinoma; Maximal estrogen inhibition; Neoplasms, Hormone-dependent; Stage IIIA breast cancer; Stage IIIB breast cancer
• 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; Estrogens; Toremifene; Atamestane; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogen Receptor Antagonists
• Other Study ID Numbers: Biomed 777-CLP-30