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

Breast Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00097344
• Other study ID #: Biomed 777-CLP-30
• Status: Terminated
• Phase: Phase 3
• First received: November 22, 2004
• Last updated: August 21, 2007
• Start date: December 2004
• Est. completion date: August 2006

Study information

• Verified date: August 2007
• Source: Intarcia Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationRussia: Pharmacological Committee, Ministry of HealthUkraine: State Pharmacological Center - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 842
• Est. completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasms
• Neoplasms, Hormone-Dependent

Intervention

Drug:
• Atamestane

• Toremifene

• Letrozole

• Aromatase inhibition

• Estrogen receptor blocker

Procedure:
• Hormone therapy

• Endocrine therapy

• Antiestrogen therapy

Locations

Country	Name	City	State
Bulgaria	Research Site	Blagoevgrad
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Shumen
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Stara Zagora
Bulgaria	Research Site	Varna
Romania	Research Site	Arad
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Bucharest
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Oradea
Romania	Research Site	Ploiesti
Romania	Research Site	Targu-Mures
Romania	Research Site	Timisoara
Russian Federation	Research Site	Arkhanglsk
Russian Federation	Research Site	Astrakhan
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Engels
Russian Federation	Research Site	Irkutsk
Russian Federation	Research Site	Kaliningrad
Russian Federation	Research Site	Kaluga
Russian Federation	Research Site	Kazan
Russian Federation	Research site	Krasnodar
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Orel
Russian Federation	Research Site	Orenburg
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Pyatigorsk
Russian Federation	Research Site	Sochi
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Syktyvkar
Russian Federation	Research Site	Tambov
Russian Federation	Research Site	Ufa
Russian Federation	Research Site	Ulyanovsk
Russian Federation	Research Site	Yaroslavl
Ukraine	Research Site	Chernigov
Ukraine	Research Site	Chernivtsy
Ukraine	Research Site	Donetsk
Ukraine	Research Site	Kharkov
Ukraine	Research Site	Kherson
Ukraine	Research Site	Khmelnitsky
Ukraine	Research Site	Lugansk
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Lviv
Ukraine	Research Site	Mariupol
Ukraine	Research Site	Odessa
Ukraine	Research Site	Sumy
Ukraine	Research Site	Ternopil
Ukraine	Research Site	Vinnitsa
United States	Research Site	Augusta	Georgia
United States	Research Site	Billings	Montana
United States	Research Site	Bristol	Tennessee
United States	Research Site	Cherry Hill	New Jersey
United States	Research Site	Chesapeake	Virginia
United States	Research Site	Columbia	South Carolina
United States	Research Site	Danville	Virginia
United States	Research Site	Detroit	Michigan
United States	Research Site	Evansville	Indiana
United States	Research Site	Flint	Michigan
United States	Research Site	Fountain Valley	California
United States	Research Site	Fresh Meadows	New York
United States	Research Site	Greenbrae	California
United States	Research Site	Greenwich	Connecticut
United States	Research Site	Hot Springs	Arkansas
United States	Research Site	Houston	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kissimmee	Florida
United States	Research Site	Lacey	Washington
United States	Research Site	Lenexa	Kansas
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Memphis	Tennessee
United States	Research Site	Miami	Florida
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Mobile	Alabama
United States	Research Site	New Albany	Indiana
United States	Research Site	Newark	New Jersey
United States	Research Site	Norfolk	Virginia
United States	Research Site	Ocala	Florida
United States	Research Site	Ogden	Utah
United States	Research Site	Pasadena	Texas
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Poway	California
United States	Research Site	Racine	Wisconsin
United States	Research Site	Reno	Nevada
United States	Research Site	Rhinelander	Wisconsin
United States	Research Site	Robbinsdale	Minnesota
United States	Research Site	Savannah	Georgia
United States	Research Site	Shreveport	Louisiana
United States	Research Site	St. Louis	Missouri
United States	Research Site	Tampa	Florida
United States	Research Site	Towson	Maryland
United States	Research Site	Tuscon	Arizona
United States	Research Site	Valhalla	New York
United States	Research Site	West Reading	Pennsylvania
United States	Research Site	Wooster	Ohio
United States	Research Site	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Intarcia Therapeutics

Countries where clinical trial is conducted

United States,  Bulgaria,  Romania,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression
Secondary	Response rate
Secondary	Safety
Secondary	Overall survival