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

• Sponsor: Intarcia Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00044291
• Collaborator: (none)
• Enrollment: 865
• Locations: 63
• Arms: 2
• Duration (Months): 43
• Patients Per Site: 13.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 865 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: Jun 1, 2002
• Actual Primary Completion Date: Jan 1, 2006
• Actual Study Completion Date: Jan 1, 2006

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Time to tumor progression [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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Midwest Internal Medicine, PLLC	Lake Havasu City	Arizona	United States	86403
2	Arizona Clinical Research Center	Tucson	Arizona	United States	85712
3	California Cancer Care, Inc.	Greenbrae	California	United States	94904-2007
4	Sharp Memorial Hospital	San Diego	California	United States	92123
5	Innovative Medical Research of South Florida Inc.	Miami Shores	Florida	United States	33138
6	Georgia Cancer Specialists	Tucker	Georgia	United States	30084
7	Maryland Hematology/Oncology Associates	Baltimore	Maryland	United States	21236
8	Oncology Care Associates, PLLC	St. Joseph	Michigan	United States	49085
9	Kansas City Oncology and Hematology Group	Kansas City	Missouri	United States	64131
10	Great Falls Clinic-Oncology West	Great Falls	Montana	United States	59405
11	Slocum-Dickson Medical Group	New Hartford	New York	United States	13413
12	Hematology Oncology Consultants, Inc.	Columbus	Ohio	United States	43235
13	Oncology Consultants	Houston	Texas	United States	77024
14	First Dynamic Healthcare Services, Inc.	Killeen	Texas	United States	76710
15	Cache Valley Cancer Treatment & Research Clinic	Logan	Utah	United States	84341
16	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
17	Western Washington Oncology Inc., P.S.	Olympia	Washington	United States	98502
18	Ottawa Regional Cancer Centre	Ottawa	Ontario	Canada	K 1H 1C4
19	Northwestern Ontario Regional Cancer Centre	Thunder Bay	Ontario	Canada	P7A7T1
20	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
21	McGill University, Department of Oncology	Montreal	Quebec	Canada	H2W1S6
22	Arkhangelsk Regional Oncology Center, Department of Chemotherapy	Arkhangelsk		Russian Federation	163045
23	Tatarstan Republican Clinical Oncology Center	Kazan		Russian Federation	420029
24	Krasnodar Regional Clinical Oncology Center, Chemotherapy Department	Krasnodar		Russian Federation	350040
25	Leningrad Regional Oncology Center	Leningrad		Russian Federation	188663
26	Lipetsk Regional Oncology Center, Department of General Oncology	Lipetsk		Russian Federation	398005
27	Blokhin Cancer Research Center, Department of Chemotherapy and Combined Treatment of Tumors	Moscow		Russian Federation	115478
28	Blokhin Cancer Research Center, Department of Chemotherapy	Moscow		Russian Federation	115478
29	Blokhin Cancer Research Center, Department of Clinical Pharmacology and Chemotherapy	Moscow		Russian Federation	115478
30	Blokhin Cancer Research Center, Department of New Antitumor Drug Research	Moscow		Russian Federation	115478
31	Hertzen Research Institute of Oncology, Department of Chemotherapy	Moscow		Russian Federation	125284
32	Central Clinical Hospital of the Ministry of Transport n.a. Semashko, Department of Chemotherapy	Moscow		Russian Federation	129128
33	Moscow City Hospital #40, Department of Chemotherapy	Moscow		Russian Federation	129301
34	Moscow City Oncology Hospital #62	Moscow		Russian Federation	143423
35	Murmansk Regional Oncology Center	Murmansk		Russian Federation	183047
36	Municipal Clinical Hospital #1, Department of Breast Tumors, Oncology Department	Novosibirsk		Russian Federation	630047
37	Medical Radiological Research Center	Obninsk		Russian Federation	249036
38	Ryazan Regional Clinical Oncology Center	Ryazan		Russian Federation	390046
39	Samara Regional Oncology Center, Department of Chemotherapy	Samara		Russian Federation	443066
40	St. Petersburg City Oncology Center	St. Petersburg		Russian Federation	197022
41	Laboratory of Thoracic Oncology, St. Petersburg Pavlov State Medical University, Research Institute of Pulmonology	St. Petersburg		Russian Federation	197089
42	Petrov Research Institute of Oncology, Department of Biotherapy and Bone Marrow Transplantation	St. Petersburg		Russian Federation	197758
43	Petrov Research Institute of Oncology, Department of Breast Cancer	St. Petersburg		Russian Federation	197758
44	Petrov Research Institute of Oncology, Department of Chemotherapy	St. Petersburg		Russian Federation	197758
45	Stavropol Regional Oncology Center, Department of Chemotherapy	Stavropol		Russian Federation	355018
46	Research Institute of Oncology, Tomsk Scientific Center, Siberian Department of the Russian Academy of Medical Sciences, Department of Chemotherapy	Tomsk		Russian Federation	634028
47	V. Novgorod Regional Oncology Center, Department of Chemotherapy	V. Novgorod		Russian Federation	173016
48	Burdenko Voronezh Medical Academy, Oncology Department, Clinical Facility: Regional Clinical Oncology Center	Voronezh		Russian Federation	394000
49	Cherkassy Regional Oncology Center, Chemotherapy Department	Cherkassy		Ukraine	18009
50	Dnepropetrovsk State Medical Academy, Oncology Department. Clinical Facility: Dnepropetrovsk City Clinical Hospital #4	Dnepropetrovsk		Ukraine	49102
51	Donetsk State Medical University. Clinical Facility: Donetsk Regional Antineoplastic Center, Mammology Department	Donetsk		Ukraine	83092
52	Ivano-Frankovsk State Medical Academy; Oncology Department Clinical Facility: Ivano-Frankovsk Regional Oncology Center	Ivano-Frankovsk		Ukraine	76000
53	Kharkov State Medical University. Clinical Facility: Grigoriev Medical Radiology Institute, Chemotherapy Department	Kharkov		Ukraine	61024
54	Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department. Clinical Facility: Kharkov Regional Clinical Oncology Dispensary, Chemotherapy Department	Kharkov		Ukraine	61070
55	Kiev Central Clinical Hospital, Ukraine Security Services, Surgery Department	Kiev		Ukraine	01021
56	Kiev Oncology Institute, Ukraine Medical Science Academy, Department of Breast Tumors	Kiev		Ukraine	03022
57	Kiev Postgraduate Studies Medical Academy. Clinical Facility: Kiev City Oncology Hospital, Chemotherapy Department	Kiev		Ukraine	03115
58	National Medical University, Oncology Department. Clinical Facility: Kiev City Oncology Hospital, Surgery Department	Kiev		Ukraine	03115
59	Krivoy Rog City Oncology Center	Krivoy Rog		Ukraine	50048
60	Lviv State Medical University, Oncology and Medical Radiology Department. Clinical Facility: Lviv State Oncology Regional Clinical Diagnostic Center, Chemotherapy Department	Lviv		Ukraine	79031
61	Odessa State Medical University, Oncology Department. Clinical Facility: Odessa Regional Oncology Center, Chemotherapy Department	Odessa		Ukraine	65055
62	Uzhgorod National University Oncology Course of Surgery Department of Postgraduate Education Faculty Clinical Facility: Zakarpatye Regional Oncology Center	Uzhgorod		Ukraine	88000
63	Zaporozhye Statue Institute of Postgraduate Training. Oncology Department; Clinical Facility: Zaporozhye Regional Oncology Center	Zaporozhye		Ukraine	69104

Sponsors and Collaborators

• Intarcia Therapeutics

Investigators

• Study Chair: Paul Goss, M.D., Princess Margaret Hospital, Canada

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Intarcia Therapeutics
• ClinicalTrials.gov Identifier: NCT00044291
• Other Study ID Numbers: Biomed 777-CLP-29
• First Posted: Aug 27, 2002
• Last Update Posted: Jul 31, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Intarcia Therapeutics: Atamestane; Toremifene; Letrozole; Aromatase inhibitor; Receptor-positive; 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: Neoplasms; Breast Neoplasms; Neoplasms, Hormone-Dependent; Toremifene; Letrozole; Hormones; Atamestane; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogen Receptor Antagonists

Study Results

No Results Posted as of Jul 31, 2015