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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00044291
Recruitment Status : Completed
First Posted : August 27, 2002
Last Update Posted : July 31, 2015
Information provided by (Responsible Party):
Intarcia Therapeutics

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.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Neoplasms, Hormone-dependent Drug: atamestane Drug: toremifene Drug: letrozole Drug: aromatase inhibition Procedure: hormone therapy Procedure: endocrine therapy Procedure: antiestrogen therapy Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 865 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Study Start Date : June 2002
Actual Primary Completion Date : January 2006
Actual Study Completion Date : January 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Letrozole

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: letrozole
Drug: aromatase inhibition
Procedure: hormone therapy
Procedure: endocrine therapy

Primary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00044291

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Sponsors and Collaborators
Intarcia Therapeutics
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Study Chair: Paul Goss, M.D. Princess Margaret Hospital, Canada
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Responsible Party: Intarcia Therapeutics Identifier: NCT00044291    
Other Study ID Numbers: Biomed 777-CLP-29
First Posted: August 27, 2002    Key Record Dates
Last Update Posted: July 31, 2015
Last Verified: July 2015
Keywords provided by Intarcia Therapeutics:
Aromatase inhibitor
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
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms, Hormone-Dependent
Neoplasms by Site
Breast Diseases
Skin Diseases
Estrogen Antagonists
Estrogen Receptor Modulators
Estrogen Receptor Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents