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

Sponsor

Intarcia Therapeutics (Industry)

Overall Status

Terminated

CT.gov ID

NCT00097344

Collaborator

(none)

842

Enrollment

104

Locations

Duration (Months)

8.1

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms Neoplasms, Hormone-Dependent	Drug: Atamestane Drug: Toremifene Drug: Letrozole Drug: Aromatase inhibition Drug: Estrogen receptor blocker Procedure: Hormone therapy Procedure: Endocrine therapy Procedure: Antiestrogen therapy	Phase 3

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 Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2004

Study Completion Date :

Aug 1, 2006

Outcome Measures

Primary Outcome Measures

Time to progression []

Secondary Outcome Measures

Response rate []
Safety []
Overall survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Mobile	Alabama	United States	36607
2	Research Site	Tuscon	Arizona	United States	85704
3	Research Site	Hot Springs	Arkansas	United States	71913
4	Research Site	Fountain Valley	California	United States	92708
5	Research Site	Greenbrae	California	United States	94904
6	Research Site	Los Angeles	California	United States	90807
7	Research Site	Poway	California	United States	92064
8	Research Site	Greenwich	Connecticut	United States	06830
9	Research Site	Jacksonville	Florida	United States	32209
10	Research Site	Kissimmee	Florida	United States	34741
11	Research Site	Miami	Florida	United States	33176
12	Research Site	Ocala	Florida	United States	34474
13	Research Site	Pembroke Pines	Florida	United States	33028
14	Research Site	Tampa	Florida	United States	33607
15	Research Site	Augusta	Georgia	United States	30901
16	Research Site	Savannah	Georgia	United States	31405
17	Research Site	Evansville	Indiana	United States	47713
18	Research Site	New Albany	Indiana	United States	47150
19	Research Site	Lenexa	Kansas	United States	66214
20	Research Site	Louisville	Kentucky	United States	40207
21	Research Site	Shreveport	Louisiana	United States	71105
22	Research Site	Towson	Maryland	United States	21204
23	Research Site	Detroit	Michigan	United States	48076
24	Research Site	Flint	Michigan	United States	48532
25	Research Site	Robbinsdale	Minnesota	United States	55422
26	Research Site	St. Louis	Missouri	United States	63128
27	Research Site	Billings	Montana	United States	59101
28	Research Site	Reno	Nevada	United States	89502
29	Research Site	Cherry Hill	New Jersey	United States	08003
30	Research Site	Newark	New Jersey	United States	07101
31	Research Site	Fresh Meadows	New York	United States	11365
32	Research Site	Valhalla	New York	United States	10595
33	Research Site	Wooster	Ohio	United States	44691
34	Research Site	Zanesville	Ohio	United States	43701
35	Research Site	Philadelphia	Pennsylvania	United States	19146
36	Research Site	West Reading	Pennsylvania	United States	19611
37	Research Site	Columbia	South Carolina	United States	29203
38	Research Site	Bristol	Tennessee	United States	37620
39	Research Site	Memphis	Tennessee	United States	38120
40	Research Site	Houston	Texas	United States	77024
41	Research Site	Pasadena	Texas	United States	77504
42	Research Site	Ogden	Utah	United States	84403
43	Research Site	Chesapeake	Virginia	United States	23320
44	Research Site	Danville	Virginia	United States	24541
45	Research Site	Norfolk	Virginia	United States	23502
46	Research Site	Lacey	Washington	United States	98503
47	Research Site	Milwaukee	Wisconsin	United States	53215
48	Research Site	Racine	Wisconsin	United States	53405
49	Research Site	Rhinelander	Wisconsin	United States	54501
50	Research Site	Blagoevgrad		Bulgaria	2700
51	Research Site	Plovdiv		Bulgaria	4004
52	Research Site	Shumen		Bulgaria	9700
53	Research Site	Sofia		Bulgaria	1233
54	Research Site	Sofia		Bulgaria	1756
55	Research Site	Stara Zagora		Bulgaria	6003
56	Research Site	Varna		Bulgaria	9010
57	Research Site	Arad		Romania	310017
58	Research Site	Brasov		Romania	500366
59	Research Site	Bucharest		Romania	22115
60	Research Site	Bucharest		Romania	22328
61	Research Site	Cluj-Napoca		Romania	400015
62	Research Site	Oradea		Romania	410032
63	Research Site	Ploiesti		Romania	100337
64	Research Site	Targu-Mures		Romania	540141
65	Research Site	Timisoara		Romania	300223
66	Research Site	Arkhanglsk		Russian Federation	163045
67	Research Site	Astrakhan		Russian Federation	414041
68	Research Site	Chelyabinsk		Russian Federation	454087
69	Research Site	Engels		Russian Federation	413115
70	Research Site	Irkutsk		Russian Federation	664035
71	Research Site	Kaliningrad		Russian Federation	236040
72	Research Site	Kaluga		Russian Federation	248007
73	Research Site	Kazan		Russian Federation	420012
74	Research site	Krasnodar		Russian Federation	350040
75	Research Site	Moscow		Russian Federation	119121
76	Research Site	Moscow		Russian Federation	121356
77	Research Site	Omsk		Russian Federation	644013
78	Research Site	Orel		Russian Federation	302020
79	Research Site	Orenburg		Russian Federation	460021
80	Research Site	Perm		Russian Federation	614066
81	Research Site	Pyatigorsk		Russian Federation	357524
82	Research Site	Sochi		Russian Federation	354057
83	Research Site	St. Petersburg		Russian Federation	191104
84	Research Site	St. Petersburg		Russian Federation	197022
85	Research Site	St. Petersburg		Russian Federation	197758
86	Research Site	Syktyvkar		Russian Federation	167904
87	Research Site	Tambov		Russian Federation	392013
88	Research Site	Ufa		Russian Federation	450054
89	Research Site	Ulyanovsk		Russian Federation	432063
90	Research Site	Yaroslavl		Russian Federation	150054
91	Research Site	Chernigov		Ukraine	14029
92	Research Site	Chernivtsy		Ukraine	58013
93	Research Site	Donetsk		Ukraine	83092
94	Research Site	Kharkov		Ukraine	61024
95	Research Site	Kherson		Ukraine	73000
96	Research Site	Khmelnitsky		Ukraine	29009
97	Research Site	Lugansk		Ukraine	91047
98	Research Site	Lutsk		Ukraine	43018
99	Research Site	Lviv		Ukraine	79031
100	Research Site	Mariupol		Ukraine	87500
101	Research Site	Odessa		Ukraine	65025
102	Research Site	Sumy		Ukraine	40005
103	Research Site	Ternopil		Ukraine	46023
104	Research Site	Vinnitsa		Ukraine	21021