Clinical trial NCT00097344: The CAT Study: Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer
Official title: Phase 3 Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Breast Neoplasms
Neoplasms, Hormone-Dependent
Keywords: 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
Lead sponsor: Intarcia Therapeutics
Sponsor class: INDUSTRY
First posted: 2004-11-23
Enrollment: 842
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to progression
Secondary outcomes:
measure: Response rate
measure: Safety
measure: Overall survival
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Tuscon
country: United States
facility: Research Site
state: Arizona
city: Hot Springs
country: United States
facility: Research Site
state: Arkansas
city: Fountain Valley
country: United States
facility: Research Site
state: California
city: Greenbrae
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Poway
country: United States
facility: Research Site
state: California
city: Greenwich
country: United States
facility: Research Site
state: Connecticut
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Kissimmee
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Ocala
country: United States
facility: Research Site
state: Florida
city: Pembroke Pines
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Savannah
country: United States
facility: Research Site
state: Georgia
city: Evansville
country: United States
facility: Research Site
state: Indiana
city: New Albany
country: United States
facility: Research Site
state: Indiana
city: Lenexa
country: United States
facility: Research Site
state: Kansas
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Towson
country: United States
facility: Research Site
state: Maryland
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Flint
country: United States
facility: Research Site
state: Michigan
city: Robbinsdale
country: United States
facility: Research Site
state: Minnesota
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: Billings
country: United States
facility: Research Site
state: Montana
city: Reno
country: United States
facility: Research Site
state: Nevada
city: Cherry Hill
country: United States
facility: Research Site
state: New Jersey
city: Newark
country: United States
facility: Research Site
state: New Jersey
city: Fresh Meadows
country: United States
facility: Research Site
state: New York
city: Valhalla
country: United States
facility: Research Site
state: New York
city: Wooster
country: United States
facility: Research Site
state: Ohio
city: Zanesville
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: West Reading
country: United States
facility: Research Site
state: Pennsylvania
city: Columbia
country: United States
facility: Research Site
state: South Carolina
city: Bristol
country: United States
facility: Research Site
state: Tennessee
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Pasadena
country: United States
facility: Research Site
state: Texas
city: Ogden
country: United States
facility: Research Site
state: Utah
city: Chesapeake
country: United States
facility: Research Site
state: Virginia
city: Danville
country: United States
facility: Research Site
state: Virginia
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Lacey
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Racine
country: United States
facility: Research Site
state: Wisconsin
city: Rhinelander
country: United States
facility: Research Site
state: Wisconsin
city: Blagoevgrad
country: Bulgaria
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Shumen
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Stara Zagora
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Arad
country: Romania
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Bucharest
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Ploiesti
country: Romania
facility: Research Site
city: Targu-Mures
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Arkhanglsk
country: Russian Federation
facility: Research Site
city: Astrakhan
country: Russian Federation
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Engels
country: Russian Federation
facility: Research Site
city: Irkutsk
country: Russian Federation
facility: Research Site
city: Kaliningrad
country: Russian Federation
facility: Research Site
city: Kaluga
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Krasnodar
country: Russian Federation
facility: Research site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Orel
country: Russian Federation
facility: Research Site
city: Orenburg
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Pyatigorsk
country: Russian Federation
facility: Research Site
city: Sochi
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Syktyvkar
country: Russian Federation
facility: Research Site
city: Tambov
country: Russian Federation
facility: Research Site
city: Ufa
country: Russian Federation
facility: Research Site
city: Ulyanovsk
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Chernigov
country: Ukraine
facility: Research Site
city: Chernivtsy
country: Ukraine
facility: Research Site
city: Donetsk
country: Ukraine
facility: Research Site
city: Kharkov
country: Ukraine
facility: Research Site
city: Kherson
country: Ukraine
facility: Research Site
city: Khmelnitsky
country: Ukraine
facility: Research Site
city: Lugansk
country: Ukraine
facility: Research Site
city: Lutsk
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Mariupol
country: Ukraine
facility: Research Site
city: Odessa
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
city: Ternopil
country: Ukraine
facility: Research Site
city: Vinnitsa
country: Ukraine
facility: Research Site
Study officials:
affiliation: Professor of Medicine, Mayo Clinic, Jacksonville, Florida
name: Edith Perez, MD
role: STUDY_CHAIR
References: