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

Phase 3
18 Years
Not Enrolling
Breast Neoplasms, Neoplasms, Hormone-Dependent

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Trial Information

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

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.

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

- 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

- 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

- Prior enrollment in this study.

Type of 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

Outcome Measure:

Time to progression

Principal Investigator

Edith Perez, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Professor of Medicine, Mayo Clinic, Jacksonville, Florida


United States: Food and Drug Administration

Study ID:

Biomed 777-CLP-30



Start Date:

December 2004

Completion Date:

August 2006

Related Keywords:

  • Breast Neoplasms
  • Neoplasms, Hormone-Dependent
  • Aromatase inhibitor
  • Atamestane
  • Breast neoplasms
  • Combined hormonal therapy
  • Complete estrogen blockade
  • Ductal breast carcinoma
  • Estrogen blocker
  • Fareston┬«
  • Femara┬«
  • First line therapy
  • Letrozole
  • Lobular breast carcinoma
  • Locally advanced breast cancer
  • Locally recurrent breast cancer
  • Maximal estrogen inhibition
  • Metastatic breast cancer
  • Neoplasms, Hormone-dependent
  • Receptor-positive
  • Stage IIIA breast cancer
  • Stage IIIB breast cancer
  • Stage IV breast cancer
  • Toremifene
  • Breast Neoplasms
  • Neoplasms
  • Neoplasms, Hormone-Dependent



Research Site Alabaster, Alabama  
Research Site Mesa, Arizona  
Research Site Bentonville, Arkansas  
Research Site Anaheim, California  
Research Site Danbury, Connecticut  
Research Site Boca Raton, Florida  
Research Site Albany, Georgia  
Research Site Bloomington, Indiana  
Research Site Hays, Kansas  
Research Site Ashland, Kentucky  
Research Site Baton Rouge, Louisiana  
Research Site Baltimore, Maryland  
Research Site Battle Kreek, Michigan  
Research Site Alexandria, Minnesota  
Research Site Branson, Missouri  
Research Site Billings, Montana  
Research Site Las Vegas, Nevada  
Research Site Belleville, New Jersey  
Research Site Albany, New York  
Research Site Akron, Ohio  
Research Site Allentown, Pennsylvania  
Research Site Charleston, South Carolina  
Research Site Chattanooga, Tennessee  
Research Site Abilene, Texas  
Research Site Ivins, Utah  
Research Site Abington, Virginia  
Research Site Auburn, Washington  
Research Site Appleton, Wisconsin